EDITORIAL ESPANOL:

====================

Hola amigos DERMAGICOS, el tema de hoy, el CARCINOMA DE CÉLULAS DE MERKEL 

tumor bastante controversial en cuanto a origen, diagnostico y tratamiento.

Estas 51 referencias bibliográficas nos detallan bien estas interrogantes. 

Dra. Hortensia García, aquí tienes la respuesta a tu pregunta en DERMLIST

sobre el MERKELIOMA !!! 

Saludos a TODOS,,, 

Dr. José Lapenta R.,,,

 EDITORIAL ENGLISH:

===================

Hello DERMAGICS friends, today's topic, the MERKEL CELL CARCINOMA quite

controversial tumor as for origin, diagnose and treatment. These 51

bibliographical references detail us well these queries. 

Dr. Hortensia Garcia, here you have the answer to your question in DERMLIST

on the MERKELIOMA!!! 

Greetings to ALL, 

Dr. José Lapenta,

************************************

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DERMAGIC/EXPRESS(38)

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EL CARCINOMA DE MERKEL /THE MERKEL CELL CARCINOMA

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1.) Merkel cell carcinoma. Diagnosis and treatment.

2.) Is aggressive surgical management justified in the treatment of

3.) Merkel cell carcinoma. Histopathology, immunohistochemistry, and

cytogenetic analysis.

4.) Merkel's cell (neuroendocrine) carcinoma of the vulva.

5.) CD44 expression in Merkel cell carcinoma may correlate with risk of

metástasis.

6.) Neuroendocrine (Merkel cell) carcinoma with an intraepidermal component.

7.) The treatment of advanced Merkel cell carcinoma. A multimodality

chemotherapy and radiation therapy treatment approach.

8.) Merkel cell tumor of the head and neck. Five new cases with

literature review.

9.) Chromosomes 1, 11, and 13 are frequently involved in karyotypic

abnormalities in metastatic Merkel cell carcinoma.

10.) Merkel cell carcinoma of the labial mucosa. An immunohistochemical and

ultrastructural study with a review of the literature on oral Merkel cell

carcinomas.

11.) Neuroendocrine carcinoma within lymph nodes in the absence of a

primary tumor, with special reference to Merkel cell carcinoma [see comments]

12.) Pagetoid intraepidermal spread in Merkel cell (primary

neuroendocrine) carcinoma of the skin.

13.) Multiple hamartoma syndrome (Cowden's disease) associated with renal

cell carcinoma and primary neuroendocrine carcinoma of the skin (Merkel

cell carcinoma).

14.) Merkel cell carcinoma. Prognosis and management.

15.) Hyperthermia and radiation therapy in the treatment of recurrent

Merkel cell tumors.

16.) Merkel cell carcinoma. Improved locoregional control with

postoperative radiation therapy.

17.) Giant neuroendocrine (Merkel cell) carcinoma of the skin.

18.) Tumor lysis syndrome in a patient with metastatic Merkel cell carcinoma.

19.) Spontaneous regression in Merkel cell (neuroendocrine) carcinoma of

the skin.

20.) Merkel cell carcinoma metastatic to the testis.

21.) The use of VP16 and cisplatin in the treatment of Merkel cell carcinoma.

22.) Radiotherapy as an adjunct in the management of Merkel cell carcinoma.

23.) Neuroendocrine (Merkel cell) carcinoma of the skin: a

clinico-morphological study of 13 cases.

24.) Merkel cell carcinoma.

25.) Merkel cell carcinoma. A successful treatment with tumor necrosis

factor.

26.) Involvement of chromosome 22 in a Merkel cell carcinoma in a patient

with a previous meningioma.

27.) Clinicopathologic correlations of cutaneous neuroendocrine Merkel

cell carcinoma.

28.) Chemotherapy for metastatic Merkel cell carcinoma. Review of the M.D.

Anderson Hospital's experience.

29.) Neuroendocrine (Merkel cell) carcinoma of the skin. Its natural

history, diagnosis, and treatment.

30.) Recurrent and metastatic cutaneous neuroendocrine (Merkel cell)

carcinoma mimicking angiosarcoma.

31.) Trabecular (Merkel cell) carcinoma of the skin. Treatment of primary,

recurrent, and metastatic disease.

32.) Chemotherapy for metastatic Merkel cell carcinoma.

33.) Electron microscopy of Merkel cell carcinoma from formalin-fixed tissue.

34.) Primary neuroendocrine (Merkel cell?) carcinoma of the skin. I. A

clinicopathologic and ultrastructural study of 43 cases.

35.) Merkel cell carcinoma of the skin: the structure and origin of normal

Merkel cells.

36.) Neuroendocrine skin carcinoma associated with calcitonin production:

a Merkel cell carcinoma?

37.) Cytokeratin 20 is a general marker of cutaneous Merkel cells while

certain neuronal proteins are absent.

38.) Neuroendocrine carcinoma of the skin (Merkel cell carcinoma). An

immunoelectron-microscopic case study.

39.) Somatostatin analogue scintigraphy. A simple and sensitive method for

the in vivo visualization of Merkel cell tumors and their metastases.

40.) Cytokeratin 20 in human carcinomas. A new histodiagnostic marker

detected by monoclonal antibodies.

41.) Merkel cell tumor of the back detected during pregnancy.

42.) Immunological studies on the occurrence and properties of

chromogranin A and B and secretogranin II in endocrine tumors.

43.) [Cervicofacial neuroendocrine Merkel cell carcinoma: radiotherapy] 

44.) p53 abnormalities are rare events in neuroendocrine (Merkel cell)

carcinoma

of the skin. An immunohistochemical and SSCP analysis. 

45.) Radiotherapy for Merkel cell carcinoma of the skin of the head and neck. 

46.) Lymph node Merkel cell carcinoma with no evidence of cutaneous

tumor--report of two cases. 

47.) Presumed choroidal metastasis of Merkel cell carcinoma. 

48.) Chemotherapy for Merkel cell carcinoma with carboplatin and etoposide. 

49.) Expression of alpha subunit of guanine nucleotide-binding protein Go in

Merkel cell carcinoma. 

50.) Deletion of chromosome arm 1p in a Merkel cell carcinoma (MCC). 

51.) The role of radiation therapy and chemotherapy in the treatment of Merkel

cell carcinoma. 

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1.) Merkel cell carcinoma. Diagnosis and treatment.

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SO - Dermatol Surg 1995 Aug;21(8):669-83

AU - Haag ML; Glass LF; Fenske NA

AD - Division of Dermatology and Cutaneous Surgery, University of South

Florida College of Medicine, Tampa 33612, USA.

PT - JOURNAL ARTICLE; REVIEW (175 references); REVIEW, ACADEMIC

AB - BACKGROUND. Merkel cell carcinoma is an uncommon malignancy of the

skin that often portends a poor prognosis. Since its first description by

Toker in 1972, a plethora of case reports and articles regarding the

etiopathogenesis and treatment have been published spanning multiple

medical and surgical disciplines. Much confusion still exists regarding the

diagnosis and treatment of this ominous tumor. OBJECT. Through extensive

review of the medical, surgical, and pathological literature, to collate

the observations of multiple investigators and summarize these findings.

METHODS. Articles from journals of multiple subspecialties were carefully

with particular emphasis placed on epidemiology, prognosis,

histology, immunohistochemistry, electron microscopy, tumor origin,

treatment, and work-up of Merkel cell carcinoma. RESULTS. Merkel cell

carcinoma is an aggressive malignant neoplasm. Local recurrence develops in

-44% of patients despite therapy. Up to three-fourths of patients

eventually develop regional nodal metastases with distant metastases

occurring in one-third of all patients. Reported overall 5-year survival

rates range from 30% to 64%. CONCLUSION. Treatment recommendations

unfortunately are based more on anecdotal than scientific data because of

the rarity of the tumor and its recognized high risk. Most authors

recommend wide local excision of the primary lesion and regional lymph node

resection if lymph nodes are palpable followed by x-irradiation of both the

postsurgical bed and lymph node basin. The role of elective lymph node

resection in the absence of clinically positive nodes remains controversial.

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2.) Is aggressive surgical management justified in the treatment of

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Merkel cell carcinoma? [see comments]

CM - Comment in: Plast Reconstr Surg 1995 Jul; 96(1):237

SO - Plast Reconstr Surg 1994 Dec;94(7):970-5

AU - Shack RB; Barton RM; De Lozier J; Rees RS; Lynch JB

AD - Department of Plastic Surgery, Vanderbilt University Medical Center,

Nashville, Tenn.

PT - JOURNAL ARTICLE

AB - Since its original description in 1972, we have seen and personally

treated a group of 15 patients with Merkel cell carcinoma at the Vanderbilt

Medical Center and the Nashville VA Hospital. We will review the

demographics, management, and clinical course of this extremely lethal but

initially benign appearing cutaneous malignancy. The majority of lesions

occur on the head and neck, followed by the extremities and trunk. Location

of the primary tumor has no effect on outcome. Despite a high mortality in

our series (10 of 15), early recognition and aggressive surgical therapy

may be the only way to prolong survival. No other adjuvant therapy has

proved effective.

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3.) Merkel cell carcinoma. Histopathology, immunohistochemistry, and

cytogenetic analysis.

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SO - J Dermatol Surg Oncol 1994 Oct;20(10):648-52; quiz 653-4

AU - Tope WD; Sangueza OP

AD - Department of Dermatology, Oregon Health Sciences University, Portland.

PT - JOURNAL ARTICLE

AB - BACKGROUND. Merkel cell carcinoma (MCC) is a cutaneous neoplasm,

histopathologically difficult to differentiate from other small blue cell

neoplasms. Immunohistochemical and ultrastructural analyses are usually

helpful in differentiating these neoplasms. Recently, cytogenetic analysis

has emerged as a potential tool in the diagnosis of solid neoplasms,

including MCC. OBJECTIVE. To describe the immunohistochemical and

cytogenetic features of a case of primary MCC and to review the

cytogenetics literature on MCC. METHODS. Formalin-fixed tissue was

processed routinely and labeled with a battery of antibodies. Metaphase

cells from fresh tissue were prepared by Giemsa banding. RESULTS.

Histopathologically, there were irregular aggregates of pyknotic cells with

little cytoplasm. Immunohistochemically, the neoplastic cells stained

positive for neurofilament, cytokeratin, neuron-specific enolase, and

epithelial membrane antigen. Leucocyte common antigen, S-100, 013, and

chromogranin were negative. Karyotyping of neoplastic cells showed loss of

chromosome Y (-Y). CONCLUSIONS. Coexpression of cytokeratin and

neurofilament is characteristic of MCC and allows it to be differentiated

from similar neoplasms. The significance of Y chromosome loss is unclear.

Further cytogenetic analyses are warranted to identify genetic mutations

significant to the pathogenesis of MCC.

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4.) Merkel's cell (neuroendocrine) carcinoma of the vulva.

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SO - Cancer 1994 Apr 15;73(8):2186-91

AU - Chen KT

AD - Department of Pathology, Saint Agnes Medical Center, Fresno,

California 93720.

PT - JOURNAL ARTICLE; REVIEW (15 references); REVIEW OF REPORTED CASES

AB - BACKGROUND. Merkel's cell carcinoma rarely arises in the vulva. It is

unclear whether those cases arising in the vulva behave differently from

the usual Merkel's cell carcinomas. METHODS. A Merkel's cell carcinoma of

the vulva was studied by light microscopy, immunohistochemistry, and

electron microscopy. The clinical data of this case and of other reported

cases are summarized and compared with those of Merkel's cell carcinoma in

general. RESULTS. This tumor showed the characteristic trabecular pattern

of Merkel's cell carcinoma. The tumor cells were immunoreactive to

low-molecular-weight cytokeratin and neuron-specific enolase. This patient

was treated initially with local excision. She died 17 months later with

progressive metastatic disease unresponsive to chemotherapy. This case

study and the review of six other cases indicate that Merkel's cell

carcinoma of the vulva is universally metastatic, both to the regional

lymph nodes and distant sites, and that it invariably follows a rapidly

fatal course. CONCLUSION. Merkel's cell carcinoma of the vulva appears to

have a biologic behavior more aggressive than that of Merkel's cell

carcinoma in general. An initial modality combining chemotherapy, with or

without irradiation, with aggressive surgery should be tried in future cases.

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5.) CD44 expression in Merkel cell carcinoma may correlate with risk of

metastasis.

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SO - J Cutan Pathol 1994 Feb;21(1):22-6

AU - Penneys NS; Shapiro S

AD - Division of Dermatology, St. Louis University School of Medicine,

Missouri 63104.

PT - JOURNAL ARTICLE

AB - We retrospectively studied 25 cases of cutaneous primary, locally

recurrent or metastatic Merkel cell carcinoma to see if expression of the

cell surface marker CD44 correlated with metastatic potential. In 3 of 6

cases in which metastasis was documented, CD44 was found on membranes of

tumor cells. Three cutaneous lesions associated with local metastasis did

not express CD44. Three primary tumors expressed CD44 but had not

disseminated at the time of this report; follow-up after excision of the

primary lesion in these cases was less than 6 months. None of the primary

or locally recurrent Merkel cell carcinomas followed longer than 6 months

(14 of 19 cases) expressed CD44. We conclude that expression of CD44 in

Merkel cell carcinoma may eventually be of some value in the assessment of

prognosis of cutaneous Merkel cell carcinoma.

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6.) Neuroendocrine (Merkel cell) carcinoma with an intraepidermal component.

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SO - Am J Dermatopathol 1993 Dec;15(6):528-33

AU - Smith KJ; Skelton HG 3d; Holland TT; Morgan AM; Lupton GP

AD - Department of Dermatopathology, Armed Forces Institute of Pathology,

Washington, D.C. 20306.

PT - JOURNAL ARTICLE

AB - We present 11 cases of primary neuroendocrine (Merkel cell) carcinoma

of the skin with an intraepidermal component that were identified in a

larger review of Merkel cell carcinomas. Among these is a case with a

follow-up of over 11 years in which the primary lesion appeared as bowenoid

dysplasia, with subsequent recurrences as intraepidermal Merkel cell

carcinoma with focal tubular differentiation, and then with dermal invasion

and lymph node metastasis. In addition to immunohistochemical markers

commonly used in the identification of Merkel cell carcinomas

(neuron-specific enolase and cytokeratin), these tumors stained with

Ber-EP4, an immunohistochemical marker used to identify carcinomas. We

believe that these histopathologic and immunohistochemical features further

confirm that Merkel cell carcinomas represent an epithelial tumor with the

potential for neuroendocrine and adnexal differentiation.

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7.) The treatment of advanced Merkel cell carcinoma. A multimodality

chemotherapy and radiation therapy treatment approach.

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SO - J Dermatol Surg Oncol 1993 Sep;19(9):860-4

AU - Fenig E; Lurie H; Klein B; Sulkes A

AD - Institute of Oncology, Beilinson Medical Center, Petah Tiqva, Israel.

PT - JOURNAL ARTICLE

AB - BACKGROUND. The optimal management of Merkel cell carcinoma has not

been clearly defined. OBJECTIVE. To describe the treatment of eight

patients who presented with Merkel cell carcinoma. METHODS. Eight patients

with advanced locoregional Merkel cell carcinoma were seen in our institute

over a 7-year period. Four patients were successfully treated by induction

chemotherapy after excisional biopsy, followed by radiotherapy. Three

patients died from widespread metastases and one from neutropenic sepsis

induced by chemotherapy. RESULTS. These cases demonstrate the potential

lethality and aggressive nature of this rare skin tumor despite its

chemosensitive and radioresponsive character. In all four patients who are

alive and disease-free, chemotherapy was given first and radiotherapy was

given as consolidation. CONCLUSION. We suggest that a multimodality

treatment approach--chemotherapy followed by radiotherapy--is indicated in

patients with advanced Merkel cell carcinoma.

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8.) Merkel cell tumor of the head and neck. Five new cases with

literature review.

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SO - Arch Otolaryngol Head Neck Surg 1993 Jul;119(7):782-6

AU - Rice RD Jr; Chonkich GD; Thompson KS; Chase DR

AD - Department of Surgery (Head and Neck Division), Loma Linda University

School of Medicine, CA.

PT - JOURNAL ARTICLE; REVIEW (29 references); REVIEW, TUTORIAL

AB - Merkel cell carcinoma (MCC) of the skin is an uncommon, but highly

aggressive neoplasm with a marked propensity for local and distant

metastasis. Despite the fact that more than half of the 600 cases of MCC

reported in the literature involved primary sites in the head and neck, MCC

has rarely been discussed in otolaryngology publications. We present five

new cases of MCC of the head and neck and summarize 89 additional cases

from the literature in which detailed treatment and survival data were

given. Our findings again emphasize the difficulty in making the initial

histopathologic diagnosis of MCC and demonstrate the necessity of early

diagnosis and multimodality treatment.

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9.) Chromosomes 1, 11, and 13 are frequently involved in karyotypic

abnormalities in metastatic Merkel cell carcinoma.

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SO - Cancer Genet Cytogenet 1993 May;67(1):65-70

AU - Leonard JH; Leonard P; Kearsley JH

AD - Queensland Radium Institute Laboratory, Queensland Institute of

Medical Research, Brisbane, Australia.

PT - JOURNAL ARTICLE

AB - We report a cytogenetic study of six Merkel cell carcinomas (MCC) in

which rearrangement of chromosome 1 was noted in four cases: two cases were

trisomic, in one case there was a reciprocal translocation between

chromosomes 1 and 5 [t(1; 5)(p36; p13)], and in the fourth case all cells

had a normal chromosome 1 and three derivatives, a del(1)(p22) and

del(1)(q21), and a translocation involving material of unknown origin to

the long arm, t(1; ?)(q21; ?). Four cases demonstrated loss of chromosome

13; in two of these, both copies were lost, and the survival for these two

patients was much longer than is common for MCC patients. Partial trisomy

of chromosome 11 was noted in two cases, and two patients demonstrated loss

of chromosome 22 in all cells examined. Although no consistent chromosome

change was noted in our cases, our data and those of previously published

reports, show that abnormalities of chromosomes 1, 11, and 13 occur in

30-47% of cytogenetic reports of this rare malignancy.

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10.) Merkel cell carcinoma of the labial mucosa. An immunohistochemical and

ultrastructural study with a review of the literature on oral Merkel cell

carcinomas.

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SO - Oral Surg Oral Med Oral Pathol 1992 Aug;74(2):193-200

AU - Vigneswaran N; Muller S; Lense E; Stacey B; Hewan-Lowe K; Weathers DR

AD - Department of Oral Pathology, Emory University School of Medicine,

Atlanta, GA.

PT - JOURNAL ARTICLE; REVIEW (32 references); REVIEW OF REPORTED CASES

AB - Merkel cell carcinoma is a rare cutaneous neuroendocrine tumor that

occurs predominantly in the head and neck region of older patients. An

88-year-old white man had an erythematous, umbilicated tumor on his lower

lip, which on histopathologic examination showed solid sheets of

infiltrating basaloid round cells with a high mitotic index. Globular,

paranuclear immunostaining for low-molecular-weight cytokeratins (Nos. 8,

18, and 19) and neurofilament was observed. On ultrastructural examination,

the tumor cells demonstrated paranuclear whorls of intermediate filament

aggregates and occasional electron-dense granules. This unique cytokeratin-

and neurofilament-staining pattern with coexpression enabled the Merkel

cell carcinoma to be differentiated from other small cell malignant tumors

that included metastatic neuroendocrine carcinomas from other regions. The

follow-up 1 year after surgery and radiation showed that the patient

remained disease free. Review of the literature revealed 11 cases of oral

Merkel cell carcinomas with a predilection for the labial mucosa of older

men. The mode of treatment and the clinical course of these cases are also

presented, with an update on therapeutic management of Merkel cell carcinomas.

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11.) Neuroendocrine carcinoma within lymph nodes in the absence of a

primary tumor, with special reference to Merkel cell carcinoma [see comments]

======================================================================

CM - Comment in: Am J Surg Pathol 1993 Jul; 17(7):746; discussion 747-8;

Comment in: Am J Surg Pathol 1993 Jul; 17(7):747; discussion 747-8; Comment

in: Am J Surg Pathol 1993 Sep; 17(9):954

SO - Am J Surg Pathol 1992 Jul;16(7):658-66

AU - Eusebi V; Capella C; Cossu A; Rosai J

AD - Istituti di Anatomia e Istologia Patologica, Bologna, Italy.

PT - JOURNAL ARTICLE

AB - We report eight cases of neuroendocrine carcinomas found within

inguinal (five cases), axillary (two cases), and submandibular (one case)

lymph nodes. The patients underwent extensive investigations, but no

primary tumor was found in any case. Although the existence of an occult or

regressed primary cannot be ruled out, the possibility of a lymph node

origin should be considered on the basis of epithelial inclusions or

anomalous carcinomatous differentiation of stem cells of the

lymphoreticular system.

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12.) Pagetoid intraepidermal spread in Merkel cell (primary

neuroendocrine) carcinoma of the skin.

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SO - Am J Surg Pathol 1992 Jun;16(6):584-92

AU - Le Boit PE; Crutcher WA; Shapiro PE

AD - Department of Pathology, University of California, San Francisco

94143-0506.

PT - JOURNAL ARTICLE

AB - Pagetoid intraepidermal spread of neoplastic cells was noted in six

cases of Merkel (primary neuroendocrine) cell carcinoma of the skin. In two

cases, the volume of the intraepidermal portion of the neoplasm was either

equal to or more extensive than the dermal component. The intraepidermal

component in all six cases was remarkable because of the following

findings: the presence of cells with scant cytoplasm arranged both

individually and as nests, sometimes along the dermoepidermal junction;

splaying of the apical portions of basal keratinocytes by solitary

neoplastic cells; incomplete rims of compressed basal keratinocytes at the

peripheries of some junctional nests; and occasional contiguity of

neuroendocrine carcinoma cells with those of Bowen's disease or solar

keratosis. These features can be used to distinguish these Merkel cell

carcinomas from other lesions that have a pagetoid pattern, even in

superficial biopsies, and immunohistochemistry can confirm the diagnosis or

resolve problematic cases. The occurrence of cutaneous neuroendocrine

carcinoma situated largely in the epidermis raises the possibility that

some of these tumors may arise from intraepidermal Merkel cells.

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13.) Multiple hamartoma syndrome (Cowden's disease) associated with renal

cell carcinoma and primary neuroendocrine carcinoma of the skin (Merkel

cell carcinoma).

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SO - Am J Clin Pathol 1992 May;97(5):705-12

AU - Haibach H; Burns TW; Carlson HE; Burman KD; Deftos LJ

AD - Department of Pathology, University of Missouri-Columbia.

PT - JOURNAL ARTICLE

AB - A case of multiple hamartoma syndrome (Cowden's disease) associated

with renal cell adenocarcinoma and primary neuroendocrine carcinoma of the

skin is described. Neither of these neoplasms has been documented

previously in association with this genodermatosis. A search for epidermal

growth factor receptor (c-erb-B protooncogene) gene abnormalities in the

kidney, liver, and thyroid, as well as in tissue of the primary

neuroendocrine carcinoma, was negative. Serum obtained from the patient

before his death contained elevated levels of both chromogranin A (2641

ng/mL; normal level, less than 20 ng/mL) and calcitonin (517 pg/mL; normal

level, less than 200 pg/mL), suggesting that the patient's principal tumor

was neuroendocrine in origin.

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14.) Merkel cell carcinoma. Prognosis and management.

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SO - Arch Surg 1991 Dec;126(12):1514-9

AU - Yiengpruksawan A; Coit DG; Thaler HT; Urmacher C; Knapper WK

AD - Department of Surgery, Memorial Sloan-Kettering Cancer Center, New

York, NY 10021.

PT - JOURNAL ARTICLE

AB - Seventy patients with Merkel cell carcinoma were treated at Memorial

Sloan-kettering Cancer Center between 1969 and 1989. The overall estimated

5-year survival rate was 64%. Factors predictive of improved survival

included head and neck site and negative lymph nodes at presentation. Local

recurrence was seen in 18 patients (26%) and did not correlate with

patient-, tumor-, or treatment-related variables. Nine patients with local

recurrence (50%) were free of disease following aggressive reoperation.

Regional nodes were involved at some point during the course of the disease

in forty-six patients (66%). Regional lymph node involvement was apparent

within 2 years of diagnosis in 40 (87%) of 46 patients in whom it occurred.

Systemic disease was nearly uniformly preceded by the appearance of nodal

metastases and was uniformly fatal regardless of subsequent therapy. This

suggests an orderly "cascade" pattern of spread for this tumor, in which

elective regional lymph node dissection may be justified. Our

recommendations for treatment include a wide excision of the primary tumor

and either elective or early therapeutic regional node dissection. The role

of adjuvant radiotherapy or chemotherapy remains unproven.

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15.) Hyperthermia and radiation therapy in the treatment of recurrent

Merkel cell tumors.

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SO - Cancer 1988 Oct 15;62(8):1479-86

AU - Knox SJ; Kapp DS

AD - Department of Radiation Oncology, Stanford University, School of

Medicine, California 94305.

PT - JOURNAL ARTICLE; REVIEW (33 references); REVIEW OF REPORTED CASES

AB - A high incidence of local recurrence, spread to regional lymph nodes,

and distant metastases has been reported after surgical excision of Merkel

cell tumors (MCT). The use of postoperative radiation therapy and/or

chemotherapy is reviewed from the literature. Despite adjuvant treatment,

local tumor recurrences frequently develop. Two patients are presented with

metastatic MCT recurrent in previously irradiated sites who had excellent

clinical responses and local control following retreatment with local

hyperthermia in conjunction with low to moderate dose radiation therapy.

These patients represent the first reported use of hyperthermia in the

management of MCT. The encouraging local responses described suggest a

potential role for the use of hyperthermia and concomitant radiation

therapy in the treatment of recurrent MCT.

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16.) Merkel cell carcinoma. Improved locoregional control with

postoperative radiation therapy.

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SO - Cancer 1991 Sep 1;68(5):1004-8

AU - Wilder RB; Harari PM; Graham AR; Shimm DS; Cassady JR

AD - Department of Radiation Oncology, University Medical Center, Tucson,

Arizona 85724.

PT - JOURNAL ARTICLE; REVIEW (23 references); REVIEW LITERATURE

AB - Between April 1981 and May 1990, 11 patients with Merkel cell

carcinoma were treated with radiation therapy in Tucson, Arizona. The

length of follow-up time from the time of irradiation ranged from 6 to 64

months. Locoregional control was maintained in seven of eight patients

treated with surgery and postoperative radiation therapy for primary or

recurrent cancer. The other three patients had bulky metastatic disease at

the time of referral. Palliation was achieved in all three patients with

radiation therapy. Hyperthermia also appeared to be beneficial in the one

patient in which it was used, and chemotherapy achieved responses in two of

four patients. These results, combined with a review of the literature,

suggest that the administration of radiation therapy postoperatively to

both the surgical bed and the draining lymph nodes improves locoregional

control and may result in long-term disease-free survival when administered

after the initial surgical resection.

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17.) Giant neuroendocrine (Merkel cell) carcinoma of the skin.

======================================================================

SO - J Am Acad Dermatol 1991 May;24(5 Pt 2):827-31

AU - Tada J; Toi Y; Yamada T; Yasutomi H; Nagao Y; Arakawa K; Arata J

AD - Department of Dermatology, Okayama University Medical School, Japan.

PT - JOURNAL ARTICLE

AB - An 82-year-old woman had a dark red to purple tumor on the left

buttock that had gradually enlarged during the last 5 years. Although

routine histologic examination was not sufficient for diagnosis,

neuroendocrine carcinoma was diagnosed by immunohistochemical and

ultrastructural studies. Immunohistochemical-positive reactions to

neurofilament, cytokeratin, neuron-specific enolase, and epithelial

membrane antigen were noted. Electron microscopically, membrane-bound,

dense core granules that yielded a positive uranaffin reaction and

intermediate filaments in the perinuclear area were observed in the

cytoplasm of most tumor cells. Desmosome-like structure between them was

also found. Approximately 6 months after local excision, metastatic lesions

developed in the regional lymph nodes and liver.

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18.) Tumor lysis syndrome in a patient with metastatic Merkel cell carcinoma.

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SO - Cancer 1991 Apr 15;67(8):2207-10

AU - Dirix LY; Prove A; Becquart D; Wouters E; Vermeulen P; Van Oosterom A

AD - Department of Medical Oncology, University Hospital Antwerp, Edegem,

Belgium.

PT - JOURNAL ARTICLE

AB - A first course of combination chemotherapy for large volume

metastatic disease in a patient with Merkel cell carcinoma resulted in a

tumor lysis syndrome. After this course a nearly complete response was

documented. This case report extends further the chemosensitivity of Merkel

cell carcinoma and demonstrates the need for tumor lysis syndrome

prophylaxis in patients with bulky disease or fast-growing tumors.

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19.) Spontaneous regression in Merkel cell (neuroendocrine) carcinoma of

the skin.

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SO - Arch Dermatol 1991 Apr;127(4):550-3

AU - Kayashima K; Ono T; Johno M; Kojo Y; Yamashita N; Matsunaga W

AD - Department of Dermatology, Kumamoto University Medical School, Japan.

PT - JOURNAL ARTICLE

AB - In two Japanese women, 68 and 88 years old, Merkel cell

(neuroendocrine) carcinoma of the face developed. Their tumors regressed

after biopsy was performed, a rare occurrence. Histological and electron

microscopic examination showed apoptosis, cellular necrosis, and an

infiltration composed mainly of lymphocytes in the tumors. These changes

may have been related to the mechanism of regression. It is interesting

that our two patients were women, as was another patient described with

Merkel cell carcinoma regression, in light of the fact that the prognosis

of this tumor is sex dependent.

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20.) Merkel cell carcinoma metastatic to the testis.

======================================================================

SO - Am J Clin Pathol 1990 Oct;94(4):384-9

AU - Ro JY; Ayala AG; Tetu B; Ordonez NG; el-Naggar A; Grignon DJ; Mackay B

AD - Department of Pathology, University of Texas M. D. Anderson Cancer

Center, Houston 77030.

PT - JOURNAL ARTICLE

AB - Tumor metastases to the testes are rare and are usually found

incidentally at autopsy or after orchiectomy for prostatic carcinoma. It is

even more unusual for testicular metastases to be clinically detected or

symptomatic. The authors report two cases of clinically detected testicular

metastases from Merkel cell carcinoma of the skin. Merkel cell carcinoma

metastatic to the testes has not been reported previously. The two tumors,

to some degree, resembled testicular lymphomas and the interstitial type of

seminoma.

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21.) The use of VP16 and cisplatin in the treatment of Merkel cell carcinoma.

======================================================================

SO - J Dermatol Surg Oncol 1990 Mar;16(3):276-8

AU - Davis MP; Miller EM; Rau RC; Johnson OE; Naille RA; Crnkovich MJ

AD - Riverside Regional Cancer Institute, Columbus, Ohio.

PT - JOURNAL ARTICLE

AB - A 70-year-old male with regionally recurrent Merkel cell cancer

obtained a complete remission with three cycles of VP16 and cisplatin. His

response was consolidated with local radiation therapy. Two additional

patients have been reported to have responded to the same combination.

Chemotherapy consisting of either cyclophosphamide, vincristine, and

doxorubicin or VP16 and cisplatin should be considered in locally recurrent

Merkel cell cancer.

======================================================================

22.) Radiotherapy as an adjunct in the management of Merkel cell carcinoma.

======================================================================

SO - Cancer 1990 Jan 1;65(1):60-4

AU - Marks ME; Kim RY; Salter MM

AD - Department of Radiation Oncology, University of Alabama, Birmingham

35233.

PT - JOURNAL ARTICLE

AB - Four patients with a diagnosis of Merkel cell carcinoma initially

underwent surgery followed by radiotherapy. Recurrent disease prompted use

of radiation in three cases. The three cases of recurrent disease

illustrate the aggressiveness of Merkel cell carcinoma and also provide

further documentation of the radiosensitivity of this tumor. Additionally,

these cases suggest that surgery alone frequently is inadequate to achieve

local control of disease.

======================================================================

23.) Neuroendocrine (Merkel cell) carcinoma of the skin: a

clinico-morphological study of 13 cases.

======================================================================

SO - Histopathology 1989 Nov;15(5):483-93

AU - Szadowska A; Wozniak L; Lasota J; Giryn I; Mirecka B; Wolska H

AD - Department of Oncology, Medical Academy of Lodz, Poland.

PT - JOURNAL ARTICLE

AB - The clinico-morphological features in 13 patients (nine female) with

neuroendocrine carcinoma of the skin are presented. The mean age was 64.9

years. The limbs were the most common site of primary tumour, followed by

the face. The clinical course was characterized by a high incidence of

regional lymph node metastases (69%) and recurrences (46%). Seven of the

patients died of tumour, with a mean survival time of 13 months.

Histologically, a solid pattern of tumour growth was most common. The cells

were usually small and uniform. Squamous cell differentiation was found in

one tumour. The cell of all tumours reacted positively for cytokeratins and

neuron-specific enolase. The positive reaction frequently had a ball-like

globular pattern, corresponding to inclusion-like bodies seen on light

microscopy and to paranuclear whorls of intermediate filaments observed on

electron microscopy. Neurosecretory granules were seen on electron

microscopy in the 11 cases examined and in one case a 'Luse body' was found

in the intercellular space.

======================================================================

24.) Merkel cell carcinoma.

======================================================================

SO - Arch Dermatol 1989 Aug;125(8):1096-100

AU - Hanke WC; Conner AC; Temofeew RK; Lingeman RE

AD - Department of Dermatology, Indiana University School of Medicine,

Indianapolis.

PT - JOURNAL ARTICLE

AB - Merkel cell carcinoma is an unusual primary cutaneous tumor with an

aggressive biologic nature. Following surgical treatment, 40% of patients

have local recurrences develop, 55% have regional lymph node metastases

develop, and 49% have distant metastases develop. We have treated four

patients with Merkel cell carcinoma; only one of the four patients was

alive and well after 2 years. Two patients died of metastatic disease, one

at 11 months following initial treatment and one at 39 months. The fourth

patient had a rapid recurrence following initial treatment and is currently

in remission following chemotherapy for regional metastases. Recent reports

indicate that chemotherapy may be helpful in treating patients with

recurrent or metastatic Merkel cell carcinoma.

======================================================================

25.) Merkel cell carcinoma. A successful treatment with tumor necrosis

factor.

======================================================================

SO - Arch Dermatol 1989 Aug;125(8):1093-5

AU - Ito Y; Kawamura K; Miura T; Ueda K; Onodera H; Takahashi H; Horikoshi

T; Sugiyama S; Takahashi M

AD - Department of Dermatology, Sapporo Medical College, Japan.

PT - JOURNAL ARTICLE

AB - A Merkel cell carcinoma of the mandibular area in a 78-year-old woman

was treated successfully by direct intratumoral administration of

recombinant human tumor necrosis factor. The patient received 2.5 x 10(5)

U/d of recombinant human tumor necrosis factor every other day. A total of

six injections (total dose, 1.5 x 10(6) U, 0.52 mg of protein) were

administered over a period of 12 days. Soon after the therapy ended, the

lesion softened and decreased in size. After 1 month, only erythema was

visible. The lesion had completely disappeared clinically and

histologically 5 months after the local injection of recombinant human

tumor necrosis factor. Neither recurrence nor metastasis has been observed

for at least 12 months following the treatment. Recombinant human tumor

necrosis factor is suggested to be effective for the treatment of Merkel

cell carcinoma.

======================================================================

26.) Involvement of chromosome 22 in a Merkel cell carcinoma in a patient

with a previous meningioma.

======================================================================

SO - Cancer Genet Cytogenet 1989 Mar;38(1):43-8

AU - Shabtai F; Sternberg A; Klar D; Reiss R; Halbrecht I

AD - B. Gattegno Research Institute, Hasharon Hospital, Golda Medical

Center, Petach Tikva, Israel.

PT - JOURNAL ARTICLE

AB - The relatively simple cytogenetic findings in an aggressive

metastatic Merkel cell carcinoma are reported. Deletion 2p was found in

100% of the cells. Nevertheless, this was considered a secondary

(metastatic?) change because the same aberration has been found in several

other kinds of malignancy. The involvement of chromosome 22 [del(22q) and

-22] in 85% of the cells seemed more intriguing, considering the fact that

the Merkel cell carcinoma followed a previous meningioma.

======================================================================

27.) Clinicopathologic correlations of cutaneous neuroendocrine Merkel

cell carcinoma.

======================================================================

SO - J Clin Oncol 1988 Dec;6(12):1863-73

AU - Pilotti S; Rilke F; Bartoli C; Grisotti A

AD - Division of Anatomic Pathology, Istituto Nazionale per lo Studio e la

Cura del Tumori, Milan, Italy.

PT - JOURNAL ARTICLE

AB - A study of 50 consecutive cases (22 men, 28 women; age range, 39 to

84 years; mean age, 65 years) of cutaneous neuroendocrine Merkel cell

carcinoma (CNC), 39 of whom had a mean follow-up of 34 months, revealed

that the prognostic significance of the histopathologic subtyping in

trabecular, solid, and diffuse variants of CNC was not as important as the

pathologic postsurgical staging in localized, regional, and extraregional

disease. The overall mortality was 23.5%. None of the 19 patients with

localized disease died of CNC, while 11% of the 24 patients with regional

disease and all seven patients with extraregional disease at presentation

died of CNC. A second primary malignancy was found to be associated with

the CNC in 15% of the cases. The clinical course in patients with localized

disease was favorable in spite of the high number of local recurrences.

Also, the presence of regional metastases was not related to an unfavorable

prognosis. In 68% of the cases the disease involved the lower limbs or

girdle. In ten cases the overt exophytic presentation of primary CNC was

replaced by the presence of tumor masses infiltrating the inguinal soft

tissues with or without nodal involvement.

======================================================================

28.) Chemotherapy for metastatic Merkel cell carcinoma. Review of the M.D.

Anderson Hospital's experience.

======================================================================

SO - Cancer 1988 Aug 15;62(4):683-5

AU - Feun LG; Savaraj N; Legha SS; Silva EG; Benjamin RS; Burgess MA

AD - Division of Medicine, M. D. Anderson Hospital and Tumor Institute,

Houston, Texas.

PT - JOURNAL ARTICLE; REVIEW (10 references); REVIEW, TUTORIAL

AB - Thirteen patients with regional or distant metastases from Merkel

cell carcinoma were treated with combination chemotherapy. Three patients

had a complete response to therapy. In two patients with nodal disease the

duration of response was 10+ and 4+ years. In addition, three patients had

a partial response, and six patients had minor responses. Chemotherapy

using a combination of drugs that are active against small cell carcinoma

of the lung is recommended in the treatment of unresectable disease in

patients with Merkel cell carcinoma; it may produce prolonged responses.

While tumor regressions as a result of chemotherapy were often dramatic,

once the disease progressed, the course of the disease often moved rapidly

downhill and proved to be fatal.

======================================================================

29.) Neuroendocrine (Merkel cell) carcinoma of the skin. Its natural

history, diagnosis, and treatment.

======================================================================

SO - Ann Surg 1988 Feb;207(2):201-7

AU - Hitchcock CL; Bland KI; Laney RG 3d; Franzini D; Harris B; Copeland

EM 3d

AD - Department of Pathology, University of Florida College of Medicine,

Gainesville.

PT - JOURNAL ARTICLE; REVIEW (66 references); REVIEW, TUTORIAL

AB - Over 400 cases of neuroendocrine (Merkel cell) carcinoma of the skin

(NCS) have been reported. This tumor continues to pose problems in

diagnosis and effective treatment for physicians unfamiliar with its

biological characteristics. Reported here are five additional cases of NCS

and the literature for this rare neoplasm is comprehensively reviewed. An

early and accurate diagnosis is made possible by combining clinical

presentation with results of histologic study, immunoperoxidase staining

for neuron-specific enolase (NSE), epithelial membrane antigen (EMA),

cytokeratins, and electron microscopy. NCS is an aggressive tumor.

Depending on the length of follow-up, up to 40% of tumors locally recur,

55% develop regional nodal metastases, and 36% undergo distant metastasis.

Survival is sex, but not age, dependent, with an overall 2-year survival

rate of 72% (males 58% vs. females 79%). No standard procedure for initial

and/or follow-up treatment for NCS exists. The authors recommend that NCS

be treated, whenever possible, using the same rationale as applied for the

treatment of squamous cell carcinoma of the skin.

======================================================================

30.) Recurrent and metastatic cutaneous neuroendocrine (Merkel cell)

carcinoma mimicking angiosarcoma.

======================================================================

SO - Arch Dermatol 1987 Oct;123(10):1368-70

AU - Tyring SK; Lee PC; Omura EF; Green LK; Merot Y

AD - Department of Dermatology, University of Alabama at Birmingham.

PT - JOURNAL ARTICLE

AB - An elderly man presented with bright red-to-purple confluent nodules

and plaques of the scalp that appeared clinically consistent with

angiosarcoma. He had undergone surgical removal of a similar lesion from

his left temple seven months before this presentation. Although routine

histologic examination was not sufficient for diagnosis, Merkel cell

carcinoma was diagnosed by immunohistochemical studies and electron

microscopy. In addition, oat cell carcinoma of the lung was excluded with a

computed tomographic scan of his chest. With chemotherapy, the recurrent

and metastatic lesions of Merkel cell carcinoma completely resolved,

rapidly recurred, and resolved a second time with chemotherapy. Eight

months following the fourth course of chemotherapy, the patient again

developed widespread cutaneous lesions. He committed suicide within one

month of this last recurrence. An autopsy revealed no primary tumor other

than of the skin.

======================================================================

31.) Trabecular (Merkel cell) carcinoma of the skin. Treatment of primary,

recurrent, and metastatic disease.

======================================================================

SO - Cancer 1986 Jan 1;57(1):178-82

AU - Raaf JH; Urmacher C; Knapper WK; Shiu MH; Cheng EW

PT - JOURNAL ARTICLE

AB - Four new patients with trabecular (Merkel cell) carcinoma of the skin

are described, and an additional 76 patients from the literature are

reviewed. The mean age of the combined group of patients was 68; 84% were

60 years or older. Primary tumors appeared most frequently on the head and

neck (44%), leg (28%), arm (16%), or buttock (9%). No primary tumor

appeared on the trunk. The rate of local recurrence was 36%, regional

metastatic disease, 53%; distant metastases, 28%; and death due to

metastatic tumor (minimally), 25%. It appears that trabecular carcinoma of

the skin is more aggressive and lethal than previously thought. The authors

recommend that patients with this tumor undergo wide resection of the

primary site and, in healthy patients, prophylactic regional node

dissection. Both radiation therapy and chemotherapy are effective in

palliating unresectable disease.

======================================================================

32.) Chemotherapy for metastatic Merkel cell carcinoma.

======================================================================

SO - Cancer 1985 Sep 1;56(5):1034-8

AU - George TK; di Sant'agnese PA; Bennett JM

PT - JOURNAL ARTICLE

AB - Merkel cell carcinomas (also known as trabecular carcinomas) are

primary cutaneous small cell neuroendocrine neoplasms with the potential to

metastasize. Control of disseminated disease is therefore important. A case

of metastatic Merkel cell carcinoma with an excellent response to

chemotherapy is presented. The regimen chosen for this case is similar to

that used for bronchogenic small cell anaplastic carcinoma. The reason for

selecting this regimen was the common neuroendocrine differentiation and

the similar histopathologic features of these two tumors. Only a few

reports have described chemotherapy for Merkel cell carcinoma and similar

agents were used. These cases are reviewed and critically analyzed.

======================================================================

33.) Electron microscopy of Merkel cell carcinoma from formalin-fixed tissue.

======================================================================

SO - J Am Acad Dermatol 1985 Mar;12(3):487-92

AU - Haneke E

PT - JOURNAL ARTICLE

AB - Merkel cell carcinomas have characteristic, but not pathognomonic,

histomorphologic features. The diagnosis can be confirmed by

immunohistochemistry studies and electron microscopy. However, differential

diagnostic problems often occur only after all tumor material has been

fixed in formalin and embedded in paraffin, which gives poor tissue

preservation for electron microscopy. Therefore, in addition to histologic

and immunohistochemical studies, parallel ultrastructural investigations

were performed on tumor specimens fixed in glutaraldehyde and routinely

processed, for electron microscopy, on formalin-fixed tissue and on

formalin-fixed paraffin blocks. Formalin fixation led to an almost complete

loss of neurosecretory granules and cell membranes; however, the

characteristic paranuclear whorls of intermediate filaments were retained

in all tumors. Merkel cell carcinomas are immunoreactive for

neuron-specific enolase (NSE), but NSE-antisera have only recently become

commercially available. Cytokeratin is demonstrable as a paranuclear clump,

and this feature was found in four out of six tumors. Thus histologic,

immunohistochemical, and electron microscopy studies of formalin-fixed

tissue are able to confirm the diagnosis of neuroendocrine Merkel cell

carcinoma.

======================================================================

34.) Primary neuroendocrine (Merkel cell?) carcinoma of the skin. I. A

clinicopathologic and ultrastructural study of 43 cases.

======================================================================

SO - Am J Surg Pathol 1985 Feb;9(2):95-108

AU - Sibley RK; Dehner LP; Rosai J

PT - JOURNAL ARTICLE

AB - The clinical and pathologic features of 43 cases of primary

neuroendocrine carcinoma of the skin are reported. These tumors arise in

the dermis and subcutaneous tissues of elderly individuals. The head and

neck are the most common primary sites followed by the lower and upper

extremities and trunk. Characteristic histologic features include round

cells with scanty amphophilic cytoplasm and vesicular nuclei with multiple

small nucleoli. The cells are arranged in sheets, solid nests, or

anastomosing trabeculae. Collections of perinuclear intermediate filaments,

cytoplasmic dense-core membrane-bound secretory granules, complex

intercellular junctions, and cytoplasmic spinous processes are the

principal fine structural features. These ultrastructural findings are

similar to those of the normal cutaneous Merkel cell. The natural history

of this neoplasm is characterized by local recurrence in 30% of cases,

regional lymph node metastases in 65% of cases, and distant metastases in

40%. One-third of the patients were dead because of their tumors. Treatment

of extensive local or distant metastatic disease with chemotherapy or

radiotherapy resulted in only short-term palliative response.

======================================================================

35.) Merkel cell carcinoma of the skin: the structure and origin of normal

Merkel cells.

======================================================================

SO - Histopathology 1983 Mar;7(2):229-49

AU - Frigerio B; Capella C; Eusebi V; Tenti P; Azzopardi JG

PT - JOURNAL ARTICLE

AB - A series of 15 Merkel cell tumours of skin is reported. They occur

dominantly on the head and neck and on the extremities of elderly women,

frequently presenting as a reddish nodule. Three cases were associated with

squamous carcinoma at the same site, an association deserving further

study. There are two main patterns: the commoner one takes the form of a

trabecular carcinoma in the dermis mimicking metastatic carcinoma,

including oat-cell carcinoma and neuroblastoma: a dissociated-cell form

mimicks malignant lymphoma. The triad of vesicular nuclei with very small

nucleoli, abundant mitotic activity and apoptosis is so characteristic as

to be virtually pathognomonic in conjunction with structural features.

Argyrophilia is common, but Bouin fixation is necessary to demonstrate it

regularly. Small round secretory granules (89 +/- 18 nm) with narrow

haloes, and an abundance of intermediate size filaments are among the

ultrastructural hallmarks. There is a close similarity between better

differentiated tumour cells and normal Merkel cells. The neural crest

origin of MC is in doubt both on the basis of studies of the development

and regeneration of MC and from the study of Merkel cell tumours.

======================================================================

36.) Neuroendocrine skin carcinoma associated with calcitonin production:

a Merkel cell carcinoma?

======================================================================

SO - Hum Pathol 1980 Sep;11(5 Suppl):586-8

AU - Johannessen JV; Gould VE

PT - JOURNAL ARTICLE

AB - An elderly woman presented with an ulcerating skin carcinoma located

over the right parietal area. It healed after local radiotherapy but

recurred locally and metastasized to the subcutaneous tissue and one

regional lymph node. Neurosecretory granules were demonstrated

ultrastructurally, and blood levels of calcitonin were repeatedly elevated.

A metastasizing medullary carcinoma of the thyroid was suspected, and a

total thyroidectomy was performed; however, no medullary carcinoma or C

cell hyperplasia could be identified. Furthermore, the calcitonin levels

remained unchanged following thyroidectomy, whereas they decreased twice

after the skin tumor or its metastases were ablated. Clinical follow-up for

over seven years revealed no other lesion that could have been responsible

for the overproduction of calcitonin. The ultrastructural features of this

skin carcinoma and its metastases, particularly the neurosecretory

granules, were reminiscent of those of the so-called Merkel cell. We

conclude that this skin carcinoma might indeed produce calcitonin, that

this tumor may be derived from Merkel cells, and that Merkel cells may

belong within the APUD system.

======================================================================

37.) Cytokeratin 20 is a general marker of cutaneous Merkel cells while

certain neuronal proteins are absent.

======================================================================

SO - J Invest Dermatol 1995 Jun;104(6):910-5

AU - Moll I; Kuhn C; Moll R

AD - Department of Dermatology, Mannheim Medical School, University of

Heidelberg, Germany.

PT - JOURNAL ARTICLE

AB - Merkel cells are difficult to identify in tissue sections. Previous

studies have used cytokeratins (CK) 8, 18, and 19 as histologic markers of

Merkel cells. However, these CKs are also expressed in some outer root

sheath keratinocytes and some early fetal epidermal cells and thus are not

truly specific of Merkel cells in general. Using selective antibodies

against a newly described CK, number 20--originally found in intestinal

epithelium and Merkel cell carcinomas--in comparison to a key protein of

neuroendocrine cells, chromogranin A, we established CK 20 as a specific

Merkel cell marker in skin of humans, pigs, and mice. CK 20 seems to be an

even more general and sensitive Merkel cell marker as compared to CgA. In

double-labeling experiments with stratified-squamous epithelial CK (numbers

5 and 13-17) and simple epithelial CK (numbers 8, 18, and 20) antibodies

evaluated by confocal laser scanning microscopy, no cell expressing CKs of

both types (i.e., no cell of so-called "transitional" character between

Merkel cells and keratinocytes) was identified in human skin. In addition,

various neuronal markers present in Merkel cell carcinomas including

neurofilaments, peripherin, nerve growth factor receptor, and neuronal cell

adhesion molecule appear to be absent in normal Merkel cells. Thus, Merkel

cells exhibit a distinct and unique marker profile, with CK 20 being of

particularly high value in various species.

======================================================================

39.) Somatostatin analogue scintigraphy. A simple and sensitive method for

the in vivo visualization of Merkel cell tumors and their metastases.

======================================================================

SO - Arch Dermatol 1992 Jun;128(6):818-21

AU - Kwekkeboom DJ; Hoff AM; Lamberts SW; Oei HY; Krenning EP

AD - Department of Medicine, University Hospital Dijkzigt, The Netherlands.

PT - JOURNAL ARTICLE

AB - BACKGROUND--Trabecular carcinomas of the skin, or Merkel cell tumors,

are aggressive neoplasms that tend to occur in sun-exposed skin. These

tumors frequently metastasize and, despite therapy, the number of

disease-related deaths is high. Ultrastructurally and immunocytochemically,

the majority of these tumors have neuroendocrine characteristics. Recently,

we described the in vivo visualization of various neuroendocrine tumors

after injection of a radiolabeled somatostatin analogue (octreotide). In

this study, we report the results of scintigraphy with radioactive-labeled

somatostatin analogues in five patients with Merkel cell tumors.

OBSERVATIONS--In all four patients in whom tumor was detected using

computed tomographic scanning and ultrasound, the tumor sites were also

demonstrated on octreotide scintigrams. In one patient, a tumor with a

diameter that was smaller than 0.5 cm could not be detected with octreotide

scintigraphy, computed tomography, or ultrasound. Using octreotide

scintigraphy we found presumed tumor spots in two patients that were not

evident when other techniques were used. CONCLUSIONS--Octreotide

scintigraphy has an equal or even greater sensitivity than computed

tomography and ultrasound for detecting Merkel cell tumors and their

metastases. Establishing the spread of the disease in this way may ensure

an optimal choice of treatment in patients with this type of tumor.

======================================================================

40.) Cytokeratin 20 in human carcinomas. A new histodiagnostic marker

detected by monoclonal antibodies.

======================================================================

SO - Am J Pathol 1992 Feb;140(2):427-47

AU - Moll R; Lowe A; Laufer J; Franke WW

AD - Institute of Pathology, University of Mainz Medical School, Federal

Republic of Germany.

PT - JOURNAL ARTICLE

AB - The authors have recently identified a new cytokeratin (CK)

polypeptide, CK 20, whose expression is almost entirely confined to the

gastric and intestinal epithelium, urothelium, and Merkel cells. Seven

monoclonal antibodies (MAbs) specific for CK 20 were raised and

characterized by applying immunoblotting and immunocytochemical screening.

All of them reacted on frozen tissue sections. A further MAb, IT-Ks20.8,

recognized CK 20 in sections of formalin-fixed, paraffin-embedded tissue

samples. A total of 711 cases of primary and metastatic cancer, mostly

carcinomas, were analyzed immunohistochemically for CK-20 expression, using

CK-20 specific guinea-pig antibodies and MAbs. The expression spectrum of

CK 20 in carcinomas resembled that seen in the corresponding normal

epithelia of origin. CK-20 positivity was seen in the vast majority of

adenocarcinomas of the colon (89/93 cases), mucinous ovarian tumors,

transitional-cell and Merkel-cell carcinomas and frequently also in

adenocarcinomas of the stomach, bile system, and pancreas. Most squamous

cell carcinomas in general and most adenocarcinomas from other sites

(breast, lung, endometrium), nonmucinous tumors of the ovary, and

small-cell lung carcinomas were essentially or completely negative. The

authors propose to use CK 20 as a diagnostic marker valuable in

distinguishing different types of carcinomas, notably when presenting as

metastases.

======================================================================

41.) Merkel cell tumor of the back detected during pregnancy.

======================================================================

SO - Plast Reconstr Surg 1990 Aug;86(2):347-51

AU - Chao TC; Park JM; Rhee H; Greager JA

AD - Department of Surgery, University of Illinois College of Medicine,

Chicago.

PT - JOURNAL ARTICLE

AB - Merkel cell tumor is an unusual, aggressive malignancy of skin that

has been considered to be derived from cutaneous Merkel cells. We are

reporting a case of Merkel cell tumor overlying the left scapula with

metastases to the thoracic spine and pleura. The tumor was found

incidentally in a 23-year-old pregnant black woman. The tumor recurred

locally 5 months after initial wide excision. Subsequently, a second wide

excision of the recurrent tumor with ipsilateral axillary dissection was

performed. The course of the disease was complicated by local recurrence

and formation of distant metastases to pleura and spine. At the end-stage

of the disease, the patient was found to have a cardiac murmur, and

echocardiography revealed a mass in the anterior wall of the right

ventricle that was suspicious for a metastatic lesion. The patient expired

from extensive distant metastases 23 months after diagnosis.

======================================================================

42.) Immunological studies on the occurrence and properties of

chromogranin A and B and secretogranin II in endocrine tumors.

======================================================================

SO - Am J Surg Pathol 1988 Nov;12(11):877-84

AU - Weiler R; Fischer-Colbrie R; Schmid KW; Feichtinger H; Bussolati G;

Grimelius L; Krisch K; Kerl H; O'Connor D; Winkler H

AD - Department of Pharmacology, University of Innsbruck, Austria.

PT - JOURNAL ARTICLE

AB - We investigated a variety of endocrine tumors for the presence of

chromogranins A and B and secretogranin II. These antigens were identified

by one- and two-dimensional immunoblotting and in some cases by

immunohistochemistry. An antigen corresponding in electrophoretic behavior

to adrenal chromogranin A was present in all types of tumors, including

insulinomas, oat cell carcinomas, and Merkel cell tumors of the skin.

Chromogranin B had a much more limited distribution. This antigen could not

be detected in parathyroid adenomas, oat cell carcinomas, or Merkel cell

tumors, either by immunoblotting and immunohistochemistry. The occurrence

of secretogranin II was similar to that of chromogranin B, with the

exception of a positive reaction in Merkel cell tumors. In benign

pheochromocytomas, all three antigens were found consistently; whereas in

two of three malignant pheochromocytomas, chromogranin B was absent. Our

study establishes that in most cases chromogranins and secretogranin in

tumors are identical to the adrenal antigens, but that these antigens are

not always stored together. Chromogranin A is the most widely distributed

marker for endocrine tumors.

======================================================================

43.) [Cervicofacial neuroendocrine Merkel cell carcinoma: radiotherapy] 

======================================================================

Author 

Volino F; Galera F; Catalano E; Di Gennaro D; Russo R 

Address 

Divisione di Otorinolaringoiatria, Ospedali Riuniti, Salerno. 

Source 

Acta Otorhinolaryngol Ital, 14(6):651-7 1994 Nov-Dec 

Abstract 

The Authors report a case of Merkel cell carcinoma of the cervicofacial

district, particular due to its clinical and evolutive characteristics. The

Merkel cell carcinoma was first identified by Toker in 1972 and is also

known as a primary neuroendocrine the or trabecular carcinoma of the skin.

The Merkel cell carcinoma is a rare aggressive skin cancer most frequently

localized in the cervicofacial district. Although in earlier reports on the

clinical history of these tumors primary emphasis was placed on their local

aggressive behaviour, it has recently become evident that these neoplasms

have a marked propensity for early dissemination. Distant metastases are

often responsible for disease-related mortality. Merkel cell carcinoma have

classically been managed with surgery alone or surgery followed by

radiation therapy. Treatment of Merkel cell carcinoma with radiation

therapy alone has usually been reserved for advanced unresectable tumors. 

======================================================================

44.) p53 abnormalities are rare events in neuroendocrine (Merkel cell)

carcinoma

of the skin. An immunohistochemical and SSCP analysis. 

======================================================================

Author 

Schmid M; Janssen K; Dockhorn-Dworniczak B; Metze D; Zelger BW; Luger TA;

Schmid KW 

Address 

Clinic of Dermatology, University of M¨unster, Germany. 

Source 

Virchows Arch, 430(3):233-7 1997 Mar 

Abstract 

The aim of the present study was to assess a possible role of the tumour

suppressor gene p53 in neuroendocrine (Merkel cell) carcinoma of the skin

with regard to tumour development and tumour progression. p53 was

investigated in a series of routinely processed Merkel cell carcinomas,

with application of four different p53 antibodies (CM-1, PAb1801, DO7, and

PAb240) to 25 carcinomas and screening for p53 mutations of exons 4-8 by

single-strand conformation polymorphism (SSCP) analysis in 9 cases. All 25

tumours in the present series showed the characteristic microscopic and

immunohistochemical features of Merkel cell carcinoma of the skin. In 5 of

the 25 Merkel cell carcinomas investigated 5-10% of tumour cell nuclei

showed a positive p53 reaction with at least one anti-p53 antibody. A few

scattered p53 positive nuclei were found in an additional 9 cases. The

remaining 11 cases completely lacked p53 immunostaining. SSCP analysis of

exons 4-8 revealed no significant alterations in the mobility shift of the

single strand DNAs in the five cases with 5-10% p53-immunoreactive tumour

nuclei or in five cases lacking p53 accumulation significant. Our results

suggest that alterations of the p53 gene play only a minor part in the

development or progression of Merkel cell carcinoma of the skin. 

======================================================================

45.) Radiotherapy for Merkel cell carcinoma of the skin of the head and neck. 

======================================================================

Author 

Suntharalingam M; Rudoltz MS; Mendenhall WM; Parsons JT; Stringer SP;

Million RR 

Address 

Department of Radiation Oncology, University of Florida College of

Medicine, Gainesville, USA. 

Source 

Head Neck, 17(2):96-101 1995 Mar-Apr 

Abstract 

BACKGROUND. Merkel cell carcinoma is a relatively rare neuroendocrine

carcinoma of the skin. It arises in the head and neck region in

approximately 50% of cases. Its aggressive behavior predisposes patients to

local-regional recurrence and distant metastases after surgical excision

alone. In this article, we describe our experience with Merkel cell

carcinoma of the head and neck. METHODS. Of 18 patients with Merkel cell

carcinoma treated in the Department of Radiation Oncology at the University

of Florida, 12 patients who had primary tumors in the head and neck region

are reported. Eight patients were treated at initial diagnosis (group A),

and four were treated at the time of local-regional recurrence (group B).

RESULTS. Local-regional control was achieved in seven of eight patients in

group A and all four patients in group B. One patient in group A and all

patients in group B developed distant metastases and eventually died of

their disease. Bone exposure developed in one patient, requiring surgical

debridement and hyperbaric oxygen treatment. CONCLUSION. Patients with

Merkel cell carcinoma of the head and neck should be treated aggressively.

Our data suggest that local-regional recurrence is a harbinger of distant

metastases. We recommend that these patients receive treatment to both the

primary site and draining lymphatics at initial presentation. The role of

chemotherapy remains unclear. 

======================================================================

46.) Lymph node Merkel cell carcinoma with no evidence of cutaneous

tumor--report of two cases. 

======================================================================

Author 

Ferrara G; Ianniello GP; Di Vizio D; Nappi O 

Address 

Servizio di Anatomia Patologica, Azienda Ospedaliera G. Rummo, Benevento,

Italy. 

Source 

Tumori, 83(5):868-72 1997 Sep-Oct 

Abstract 

We report two cases of Merkel cell carcinoma within inguinal and axillary

lymph nodes, respectively, showing no clinico-pathologic evidence of a

primary (extranodal) tumor; one of our patients was alive with no evidence

of disease five years and ten months after the surgical excision of the

neoplasm with no postoperative chemotherapy. The diagnosis of nodal Merkel

cell carcinoma needs to be supported by a careful immunohistochemical

study: in fact, cytokeratin- and neurofilament-positive paranuclear "dots",

as well as epithelial antigens and neuroendocrine markers may be variably

expressed in tumor cells, thus requiring the application of a complete

antibody panel. In the presence of a nodal Merkel cell tumor, an exhaustive

clinico-radiologic search for a primary tumor must be carried out. After

the exclusion of any reasonable starting point of the neoplasm, a

provisional diagnosis of "primary" nodal Merkel cell carcinoma may be

acceptable; since a primary extracutaneous tumor is expected to follow a

less aggressive course than a metastatic one, follow-up data may provide

indications as to the truly extracutaneous origin of Merkel cell carcinoma. 

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47.) Presumed choroidal metastasis of Merkel cell carcinoma. 

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Author 

Small KW; Rosenwasser GO; Alexander E 3d; Rossitch G; Dutton JJ 

Address 

Duke University Medical Center, Durham, NC 27712. 

Source 

Ann Ophthalmol, 22(5):187-90 1990 May 

Abstract 

Merkel cell carcinoma is a rare skin tumor of neural crest origin and is

part of the amine precursor uptake and decarboxylase system. It typically

occurs on the face of elderly people. Distant metastasis is almost

uniformly fatal. Choroidal metastasis, to our knowledge, has not been

described. We report a patient with Merkel cell carcinoma who had a

synchronous solid choroidal tumor and a biopsy-proven brain metastasis. Our

56-year-old patient presented with a rapidly growing, violaceous

preauricular skin tumor. Computed tomography of the head disclosed

incidental brain and choroidal tumors. Light and electron microscopy of

biopsy specimens of both the skin and the brain lesions showed Merkel cell

carcinoma. Ophthalmoscopy, fluorescein angiography, and A and B echography

revealed a solid choroidal mass. The brain and skin tumors responded well

to irradiation. A radioactive episcleral plaque was applied subsequently to

the choroidal tumor. All tumors regressed, and the patient was doing well

28 months later. To our knowledge this is the first case of presumed

choroidal metastasis of Merkel cell carcinoma. 

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48.) Chemotherapy for Merkel cell carcinoma with carboplatin and etoposide. 

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Author 

Pectasides D; Moutzourides G; Dimitriadis M; Varthalitis J; Athanassiou A 

Address 

1st Department of Medical Oncology, Metaxas Memorial Cancer Hospital,

Piraeus, Greece. 

Source 

Am J Clin Oncol, 18(5):418-20 1995 Oct 

Abstract 

Merkel cell carcinoma is a rare malignant tumor of the skin. We treated

three patients with Merkel call carcinoma with the combination of

carboplatin and etoposide, which have been mostly used in the treatment of

small cell lung carcinoma. Two patients experienced partial remission of

short duration. The third patient received the combination on an adjuvant

basis but relapse occurred briefly. Two of these patients failed to respond

to second-line chemotherapy with cisplatin, ifosfamide, and epirubicin. The

patient who had the first-line treatment on an adjuvant basis, responded

completely with the second-line chemotherapy plus radiotherapy and remains

disease-free for 5+months. Merkel cell carcinoma appears to be a sensitive

tumor to chemotherapeutic regimens used for small cell lung carcinoma, but

the responses are often brief. 

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49.) Expression of alpha subunit of guanine nucleotide-binding protein Go in

Merkel cell carcinoma. 

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Author 

Uhara H; Wang YL; Matsumoto S; Kawachi S; Saida T 

Address 

Department of Dermatology, Shinshu University School of Medicine, Nagano,

Japan. 

Source 

J Cutan Pathol, 22(2):146-8 1995 Apr 

Abstract 

The alpha subunit of guanine nucleotide-binding protein Go (Go alpha),

which was initially isolated from bovine brain, interacts with muscarinic

cholinergic receptors and regulates neuronal calcium channels. Go alpha is

known to be localized in neural tissues, some endocrine cells, and

neuroendocrine tumors. We have immunohistochemically investigated the

expression of Go alpha in 4 cases of Merkel cell carcinoma using the method

of microwave treatment. In all cases of Merkel cell carcinoma, Go alpha was

consistently detected on the plasma membrane and cytoplasm of the tumor

cells. Nerve fibers in the skin were also positive for Go alpha, but other

epidermal or dermal components such as keratinocytes, melanocytes,

fibroblasts, or lymphoid cells were negative. Tumor cells of squamous cell

carcinoma, cutaneous lymphoma, sweat gland carcinoma, and malignant

melanoma were negative for Go alpha. The present study indicates that Go

alpha may be a useful immunohistochemical marker of Merkel cell carcinoma. 

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50.) Deletion of chromosome arm 1p in a Merkel cell carcinoma (MCC).

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Author 

Gibas Z; Weil S; Chen ST; McCue PA 

Address 

Department of Pathology and Cell Biology, Thomas Jefferson University,

Philadelphia, Pennsylvania. 

Source 

Genes Chromosomes Cancer, 9(3):216-20 1994 Mar 

Abstract 

A case of neuroendocrine skin carcinoma (Merkel cell carcinoma) with a

deletion of the short arm of chromosome 1 (1p) as the sole chromosomal

abnormality was examined. The tumor originated in the skin of the left knee

of a 67-year-old man. Histopathologic study showed an undifferentiated

small cell tumor which expressed neuron-specific enolase, chromogranin, and

cytokeratin (CAM 5.2). Cytogenetic analysis of a lymph node metastasis from

the groin showed a pseudodiploid cell population with a deletion of the

short arm of chromosome 1 as the only abnormality: 46,XY,del(1)(p36.1). In

situ hybridization with the D1Z2 probe specific for the terminal band of 1p

confirmed the terminal deletion. This is the first case of Merkel cell

carcinoma in which only one chromosomal abnormality has been observed. Loss

of the terminal portion of 1p suggests that a tumor suppressor gene on 1p

plays a role in the pathogenesis of Merkel cell carcinoma. 

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51.) The role of radiation therapy and chemotherapy in the treatment of Merkel

cell carcinoma. 

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Author 

Fenig E; Brenner B; Katz A; Rakovsky E; Hana MB; Sulkes A 

Address 

Institute of Oncology, Rabin Medical Center, Beilinson Campus, Petah Tiqva

and Sackler School of Medicine, Tel Aviv University, Israel. 

Source 

Cancer, 80(5):881-5 1997 Sep 1 

Abstract 

BACKGROUND: Merkel cell carcinoma is a rare and highly aggressive skin

tumor. The purpose of this study was to determine the role of radiation

therapy and chemotherapy in the treatment of patients with Merkel cell

carcinoma. METHODS: A retrospective analysis of 27 patients treated at

Rabin Medical Center in Israel is presented, focusing on the treatment

details. Data for 40 patients (the authors' 27 patients and an additional

13 patients from the Israeli Cancer Registry), were analyzed for prognostic

factors using univariate and multivariate analyses. RESULTS: Univariate

analyses revealed regional lymph node involvement and the coexistence of a

second primary tumor as unfavorable prognostic factors. On multivariate

analysis, only lymph node involvement showed borderline statistical

significance. Radiation therapy was highly effective when given as

consolidation after surgery or chemotherapy. In 11 patients irradiated

effectively, only 1 (9%) in-field recurrence occurred. Radiation therapy

yielded responses in 15 of 15 measurable sites (5 complete responses and 10

partial responses). Chemotherapy produced responses in 18 of 26 patients

(69%), mostly complete (41%). However, in the absence of radiation therapy,

the responses were short lived. CONCLUSIONS: These data support the use of

combined treatment with chemotherapy followed by radiation therapy for

patients with advanced locoregional Merkel cell carcinoma. In patients with

metastatic disease, chemotherapy as well as radiotherapy can provide

effective palliation. Further large scale investigations are warranted to

confirm this approach. 

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DATA-MÉDICOS/DERMAGIC-EXPRESS No (38) 12/02/99 DR. JOSE LAPENTA R. 

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Produced by Dr. José Lapenta R. Dermatologist

Venezuela 1.998-2.024

Producido por Dr. José Lapenta R. Dermatólogo
Venezuela 1.998-2.024

Tlf: 0414-2976087 - 04127766810