Merkel Cell Carcinoma with Pagetoid Spread Ludvik R. Donner, MD, PhD, V. 0. Speights, DO, and Raymond A. Trompler, MD
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Department of Pathology, Scott and White Clinic, Scott, S h m o o d and B r i n d b y Foundation, Texas A&M University School of Medicine, 2401 South 31st Street, m p b , lkms 76508 USA
A case of Merkel cell carcinoma showing epidermotropism is presented. The neoplastic cells displayed dotlike immunoreactivity for cytokeratins and strong imrnunoreactivity for neuron-specificenolase. Although no neuroendocrine granules were found, characteristic paranuclear fibrous bodies were present.
KEY WORDS: immunohistochernistrK Merkel cell carcinoma, ultrastructure.
CLINICAL HISTORY A 70-year-old white man with a history of multiple basal cell carcinomas and squamous cell carcinomas of the face and the neck during past 35 years and a spindle cell sarcoma of the right cheek in 1986 developed a tumor in the right retroauricular region, which was excised in December 1987. The tumor recurred twice (in February 1988 and in June 1989) and metastasized to the regional cervical lymph nodes in February 1989. The presence of multiple metastases in the liver was discovered by computed tomography in December 1989. The patient was discharged to his family physician the same month with a poor short-term prognosis and subsequently expired in February 1990.
PATHOLOGIC FINDINGS Light Microscopy The primary tumor was present in the dermis, spread along rete ridges in pagetoid fashion, invaded the epidermis, and was present in the dermal lymphatics. The neoplastic cells were small with oval nuclei and inconspicuous nucleoli. Mitoses were numerous. The tumor contained a few disAddress corremondence to L R Donner
Crete squamous foci (Fig. 1). The histologic features of the recurrent and metastatic tumors were similar. The metastatic tumor in the cervical lymph nodes displayed the geographic pattern of necrosis.
Immunohistochemistry The primary, recurrent, and metastatic tumor cells showed strong immunoreactivity for neuron-specific enolase and strong, paranuclear, dotlike immunoreactivity for cytokeratins (Figs. 2 and 3). No immunostaining for Leu-7 and neurofilaments was observed.
Electron Microscopy Occasional tumor cells contained paranuclear fibrous bodies and desmosomelike junctions. No neuroendocrine granules were found (Fig. 4).
DISCUSSION Merkel cell carcinoma typically involves the dermis and extends into the subcutis; only a few cases where the tumor displayed connection with the epidermis have been de~cribed.’.~ Epidermal invasion is a rarity; only three such cases have been reported.6 Paranuclear dotlike immunoreactivity for cytokeratins, strong immunoreactivity for neuron-specific en~lase,’-’~and
Ultrastructural Pathology, 16:25-28, 1 9 9 2 Copyright
0 1992 by Hemisphere Publishing Corporation
25
Ultrastruct Pathol Downloaded from informahealthcare.com by University of Sydney on 01/01/15 For personal use only.
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L. R. Donner et al
FIG. 1 Primary tumor. Hematoxylin and eosin, x 3.
FIG. 2 Intense immunostaining of the primary tumor for neuron-specific enolase. Note the presence of pagetoid spread and epidermal invasion, x 25.
Ultrastruct Pathol Downloaded from informahealthcare.com by University of Sydney on 01/01/15 For personal use only.
Merkel Cell Carcinoma
FIG. 3 Intense paranuclear dotlike imrnunostaining of the primary tumor for cytokeratins IAEl/AE31, x 250.
FIG. 4 Paranuclear fibrous body in the recurrent tumor, x 10,000.
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L. R. Donner et al
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endocrine (Merkel cell?) carcinoma of the skin. the resence of paranuclear fibrous bodI, A clinicopathologic and ultrastructural study ies5. are characteristic features of this tuof 43 cases. A m J Surg Pathol. 1985;9:95mor. Dense-core granules, although 108. present in the majorit of tumors, cannot 6. Rocamora A, Badia N, Vives R, Carrillo R, UIloa J, Led0 A. Epidermotropic primary neuroalways be i d e n t i f i e ~ L ~ few , ~ A foci of squaendocrine (Merkel cell) carcinoma of the skin mous differentiation were present in our with Pautrier-like microabscesses. Report of case. three cases and review of the literature. J Am The association of Merkel cell carciAcad Dermatol. 1987; 16: 1163-1 168. 7. Sibley RK, Dahl D. Primary neuroendocrine noma with overlying Bowen disease, or (Merkel cell?) carcinoma of the skin. II. An admixture of the tumor with squamous immunocytochemical study of 21 cases. A m J carcinoma, occurs in occasional Surg Pathol. 1985;9: 109-1 16. cases.3-5,1 1-14 Continuity of the tumor with 8. Battifora H, Silva EG. The use of antikeratin the epidermis and even epidermal invasion antibodies in the immunohistochemical distinction between neuroendocrine (Merkel cell) carare part of the histologic spectrum of cinoma of the skin, lymphoma, and oat cell Merkel cell carcinoma and should not decarcinoma. Cancer. 1986;58: 1040- 1046. tract from making a correct diagnosis. 9. Hall PA, d'Ardenne AJ, Butler MG, e t al. CytoLate Note: Another case of epidermokeratin and laminin immunostaining in the diagnosis of cutaneous neuro-endocrine (Merkel tropic Merkel cell carcinoma has been recell) tumours. Histopathology 1986; 10: 1179ported: Gillham SL, Hurt, MA, Morrison 1190. RG. Epidermotropic neuroendocrine carci- 10. Moll R, Osborn M, Hartschuh W, Moll I, Mahrle noma: recognition and differential diagnoG, Weber K. Variability of expression and arsis with other cutaneous small blue cell rangement of cytokeratin and neurofilaments in cutaneous neuroendocrine carcinomas malignancies. Am J Clin Pathol. 1990;94: (Merkel cell tumors): immunocytochemical and 496-497 (abstract).
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P
REFERENCES 1. Sidhu GS, Feiner H, Flotte TJ, Mullins JD, Schaefler K, Schultenover SJ. Merkel cell neoplasms. Histology, electron microscopy, biology, and histogenesis. A m J Dermatopathol. 1980;2:101-119. 2. Silva E, Mackay B. Neuroendocrine (Merkel cell) carcinoma of the skin: an ultrastructural study of nine cases. Ultrastruct Pathol. 198 1;2: 1-9. 3. Gomez LG, DiMaio S, Silva EG, Mackay B. Association between neuroendocrine (Merkel cell) carcinoma and squamous carcinoma of the skin. A m J S u r g Pathol. 1983;7:171-177. 4. Gould VE, Moll R, Moll I, Lee I, Franke WW. Neuroendocrine (Merkel) cells of the skin: hyperplasias, dysplasias, and neoplasms. Lab Invest. 1985;52:334-353. 5. Sibley RK, Dehner Ll? Rosai J. Primary neuro-
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biochemical analysis of twelve cases. Ultrastruct Pathol. 1986;10:473-495. Tang C-K, Toker C, Nedwich A, Zaman AN. Unusual cutaneous carcinoma with features of small cell (oat cell-like) and squamous cell carcinomas. A variant of malignant Merkel cell neoplasm. A m J Dermatopathol. 1982;4:537548. Frigerio B, Capella C, Eusebi V, Tenti P, Azzopardi JG. Merkel cell carcinoma of the skin: the structure and origin of normal Merkel cells. Histopathology 1983;7:229-249. Layfield L. Ulrich T, Liao S, Barr R, Cheng L, Lewin KL. Neuroendocrine carcinoma of the skin: an immunohistochemical study of tumor markers and neuroendocrine products. J Cutan Pathol. 1986; 13:268-273. Gould E, Albores-Saavedra J, Dubner B, Smith W, Payne CM. Eccrine and squamous differentiation in Merkel cell carcinoma. An immunohistochemical study. A m J Surg Pathol. 1988;12:768-772.
Ultrastruct Pathol Downloaded from informahealthcare.com by University of Sydney on 01/01/15 For personal use only.
Department of Pathology, Scott and White Clinic, Scott, S h m o o d and B r i n d b y Foundation, Texas A&M University School of Medicine, 2401 South 31st Street, m p b , lkms 76508 USA
A case of Merkel cell carcinoma showing epidermotropism is presented. The neoplastic cells displayed dotlike immunoreactivity for cytokeratins and strong imrnunoreactivity for neuron-specificenolase. Although no neuroendocrine granules were found, characteristic paranuclear fibrous bodies were present.
KEY WORDS: immunohistochernistrK Merkel cell carcinoma, ultrastructure.
CLINICAL HISTORY A 70-year-old white man with a history of multiple basal cell carcinomas and squamous cell carcinomas of the face and the neck during past 35 years and a spindle cell sarcoma of the right cheek in 1986 developed a tumor in the right retroauricular region, which was excised in December 1987. The tumor recurred twice (in February 1988 and in June 1989) and metastasized to the regional cervical lymph nodes in February 1989. The presence of multiple metastases in the liver was discovered by computed tomography in December 1989. The patient was discharged to his family physician the same month with a poor short-term prognosis and subsequently expired in February 1990.
PATHOLOGIC FINDINGS Light Microscopy The primary tumor was present in the dermis, spread along rete ridges in pagetoid fashion, invaded the epidermis, and was present in the dermal lymphatics. The neoplastic cells were small with oval nuclei and inconspicuous nucleoli. Mitoses were numerous. The tumor contained a few disAddress corremondence to L R Donner
Crete squamous foci (Fig. 1). The histologic features of the recurrent and metastatic tumors were similar. The metastatic tumor in the cervical lymph nodes displayed the geographic pattern of necrosis.
Immunohistochemistry The primary, recurrent, and metastatic tumor cells showed strong immunoreactivity for neuron-specific enolase and strong, paranuclear, dotlike immunoreactivity for cytokeratins (Figs. 2 and 3). No immunostaining for Leu-7 and neurofilaments was observed.
Electron Microscopy Occasional tumor cells contained paranuclear fibrous bodies and desmosomelike junctions. No neuroendocrine granules were found (Fig. 4).
DISCUSSION Merkel cell carcinoma typically involves the dermis and extends into the subcutis; only a few cases where the tumor displayed connection with the epidermis have been de~cribed.’.~ Epidermal invasion is a rarity; only three such cases have been reported.6 Paranuclear dotlike immunoreactivity for cytokeratins, strong immunoreactivity for neuron-specific en~lase,’-’~and
Ultrastructural Pathology, 16:25-28, 1 9 9 2 Copyright
0 1992 by Hemisphere Publishing Corporation
25
Ultrastruct Pathol Downloaded from informahealthcare.com by University of Sydney on 01/01/15 For personal use only.
26
L. R. Donner et al
FIG. 1 Primary tumor. Hematoxylin and eosin, x 3.
FIG. 2 Intense immunostaining of the primary tumor for neuron-specific enolase. Note the presence of pagetoid spread and epidermal invasion, x 25.
Ultrastruct Pathol Downloaded from informahealthcare.com by University of Sydney on 01/01/15 For personal use only.
Merkel Cell Carcinoma
FIG. 3 Intense paranuclear dotlike imrnunostaining of the primary tumor for cytokeratins IAEl/AE31, x 250.
FIG. 4 Paranuclear fibrous body in the recurrent tumor, x 10,000.
27
L. R. Donner et al
28
endocrine (Merkel cell?) carcinoma of the skin. the resence of paranuclear fibrous bodI, A clinicopathologic and ultrastructural study ies5. are characteristic features of this tuof 43 cases. A m J Surg Pathol. 1985;9:95mor. Dense-core granules, although 108. present in the majorit of tumors, cannot 6. Rocamora A, Badia N, Vives R, Carrillo R, UIloa J, Led0 A. Epidermotropic primary neuroalways be i d e n t i f i e ~ L ~ few , ~ A foci of squaendocrine (Merkel cell) carcinoma of the skin mous differentiation were present in our with Pautrier-like microabscesses. Report of case. three cases and review of the literature. J Am The association of Merkel cell carciAcad Dermatol. 1987; 16: 1163-1 168. 7. Sibley RK, Dahl D. Primary neuroendocrine noma with overlying Bowen disease, or (Merkel cell?) carcinoma of the skin. II. An admixture of the tumor with squamous immunocytochemical study of 21 cases. A m J carcinoma, occurs in occasional Surg Pathol. 1985;9: 109-1 16. cases.3-5,1 1-14 Continuity of the tumor with 8. Battifora H, Silva EG. The use of antikeratin the epidermis and even epidermal invasion antibodies in the immunohistochemical distinction between neuroendocrine (Merkel cell) carare part of the histologic spectrum of cinoma of the skin, lymphoma, and oat cell Merkel cell carcinoma and should not decarcinoma. Cancer. 1986;58: 1040- 1046. tract from making a correct diagnosis. 9. Hall PA, d'Ardenne AJ, Butler MG, e t al. CytoLate Note: Another case of epidermokeratin and laminin immunostaining in the diagnosis of cutaneous neuro-endocrine (Merkel tropic Merkel cell carcinoma has been recell) tumours. Histopathology 1986; 10: 1179ported: Gillham SL, Hurt, MA, Morrison 1190. RG. Epidermotropic neuroendocrine carci- 10. Moll R, Osborn M, Hartschuh W, Moll I, Mahrle noma: recognition and differential diagnoG, Weber K. Variability of expression and arsis with other cutaneous small blue cell rangement of cytokeratin and neurofilaments in cutaneous neuroendocrine carcinomas malignancies. Am J Clin Pathol. 1990;94: (Merkel cell tumors): immunocytochemical and 496-497 (abstract).
Ultrastruct Pathol Downloaded from informahealthcare.com by University of Sydney on 01/01/15 For personal use only.
P
REFERENCES 1. Sidhu GS, Feiner H, Flotte TJ, Mullins JD, Schaefler K, Schultenover SJ. Merkel cell neoplasms. Histology, electron microscopy, biology, and histogenesis. A m J Dermatopathol. 1980;2:101-119. 2. Silva E, Mackay B. Neuroendocrine (Merkel cell) carcinoma of the skin: an ultrastructural study of nine cases. Ultrastruct Pathol. 198 1;2: 1-9. 3. Gomez LG, DiMaio S, Silva EG, Mackay B. Association between neuroendocrine (Merkel cell) carcinoma and squamous carcinoma of the skin. A m J S u r g Pathol. 1983;7:171-177. 4. Gould VE, Moll R, Moll I, Lee I, Franke WW. Neuroendocrine (Merkel) cells of the skin: hyperplasias, dysplasias, and neoplasms. Lab Invest. 1985;52:334-353. 5. Sibley RK, Dehner Ll? Rosai J. Primary neuro-
11.
12.
13.
14.
biochemical analysis of twelve cases. Ultrastruct Pathol. 1986;10:473-495. Tang C-K, Toker C, Nedwich A, Zaman AN. Unusual cutaneous carcinoma with features of small cell (oat cell-like) and squamous cell carcinomas. A variant of malignant Merkel cell neoplasm. A m J Dermatopathol. 1982;4:537548. Frigerio B, Capella C, Eusebi V, Tenti P, Azzopardi JG. Merkel cell carcinoma of the skin: the structure and origin of normal Merkel cells. Histopathology 1983;7:229-249. Layfield L. Ulrich T, Liao S, Barr R, Cheng L, Lewin KL. Neuroendocrine carcinoma of the skin: an immunohistochemical study of tumor markers and neuroendocrine products. J Cutan Pathol. 1986; 13:268-273. Gould E, Albores-Saavedra J, Dubner B, Smith W, Payne CM. Eccrine and squamous differentiation in Merkel cell carcinoma. An immunohistochemical study. A m J Surg Pathol. 1988;12:768-772.
