| Abstract|| |
Merkel cell carcinoma (MCC) is a rare, clinically aggressive neuroendocrine carcinoma of the skin; MCC is 40 times less common as compared to melanoma. The most frequently reported sites have been the head and neck, extremities, and trunk. Potential mimics include malignant melanoma, lymphoma, or metastatic small cell (neuroendocrine) carcinomas. Histopathology of MCC resembles small cell carcinoma both morphologically and on IHC. The possible cell of origin was proposed as the Merkel cell, which functions as a mechanoreceptor. It has a high chance of local recurrence, regional and distant spread. In recent times, Merkel cell polyomavirus has been implicated as the causative agent for this tumor. The same agent has a reported etiologic association with other skin lesions, including seborrheic keratosis.
Keywords: Merkel, neuroendocrine, polyoma, seborrheic, skin
|How to cite this article:|
Anand MS, Krishnamurthy S, Ravindranath S, Ranganathan J. Merkel cell carcinoma with seborrheic keratosis: A unique association. Indian J Pathol Microbiol 2018;61:101-2
|How to cite this URL:|
Anand MS, Krishnamurthy S, Ravindranath S, Ranganathan J. Merkel cell carcinoma with seborrheic keratosis: A unique association. Indian J Pathol Microbiol [serial online] 2018 [cited 2019 Dec 13];61:101-2. Available from: http://www.ijpmonline.org/text.asp?2018/61/1/101/228186
| Introduction|| |
We present here a unique case of a 66-year-old female with adjoining Merkel cell carcinoma (MCC) and seborrheic keratosis (SK). MCC is lethal in 33% of cases. MCC is frequently misdiagnosed during clinical presentation. An adjoining SK, as seen in the present case, can be a further misleading lesion as it has a contrasting clinical appearance. A common viral etiological agent, the Merkel cell polyomavirus (MCPyV), could suggest a cause and effect relationship in the future.
| Case Report|| |
An elderly female presented with history of a mole in the epigastric region. She noticed a recent increase in its size over the past 15 days. The lesion was excised in toto and submitted for pathologic examination.
Gross examination revealed a single skin covered fibrofatty tissue measuring 3.5 cm × 3 cm × 2 cm, the center of which shows an elevated warty lesion measuring 1.5 cm.
Microscopically, the superficial portion revealed orthokeratosis, acanthosis, numerous horn cysts, and squamous eddies [Figure 1] and [Figure 2]. A malignant tumor was seen in the adjoining superficial dermis – abutting and ironing out the overlying epidermis [Figure 2]. The cells were arranged both diffusely and as infiltrating cords. The cells were small round having scanty to absent cytoplasm and coarsely stippled chromatin [Figure 3]. Brisk mitotic activity was seen. There was no ulceration. Excision margins were clear.
|Figure 1: Whole mount of normal skin (A) seborrheic keratosis (B) and the infiltrative Merkel cell carcinoma (C) in continuum, scanner view|
Click here to view
|Figure 2: Seborrheic keratosis with underlying Merkel cell carcinoma, H and E, ×100|
Click here to view
|Figure 3: Merkel cell carcinoma with small round cells having scanty to absent cytoplasm, coarsely stippled chromatin. Brisk mitoses are noted. H and E, ×400|
Click here to view
- CK20, synaptophysin, and chromogranin showed strong positivity in tumor cells
- CK7 and MIC-2 were negative
- CK20 revealed characteristic dot-like paranuclear staining.
The diagnosis of MCC and SK was rendered.
| Discussion|| |
MCC is a rare, highly aggressive skin cancer with rapidly increasing incidence since last few decades. The most significant features can be summarized in the acronym, “AEIOU:”
- Expanding rapidly
- Older than 50 years
- UV-exposed skin site.
The incidence of MCC is increasing alarmingly (almost tripled) in the recent 20 years, with 400 cases being added annually in the USA alone. Local recurrence rate of 25%–44% (higher than melanoma), high regional lymph node spread of 10%–45%, and mortality rates of 72% at 2 years imply a need for aggressive multidisciplinary diagnostic and therapeutic management with the much acknowledged importance of sentinel lymph node biopsy.
MCPyV has been detected in over 80% of cases of MCC. In another study, MCPyV sequences were detected in 64% MCC and 16% SK. MCPyV-associated transformation of Merkel cell to MCC involves (1) MCPyV DNA genomic integration and (2) large T antigen mutation. The T antigens of MCPyV are the most important proteins encoded by polyomavirus for their life within the cell. Expression of oncogenic T antigen is mandatory for the survival and growth of MCPyV-positive MCC cell lines.
The incidence of Merkel cell hyperplasia and MCC in situ which are “benign” cytologically and with the CK20 staining pattern (uniform, lacking the perinuclear dot-like pattern) has been described thrice earlier in the literature, in cases of SK. Speculation of a benign counterpart (Merkel cell epithelioma) in continuum with the same spectrum also gives further reference to a possible melanoma-like sequential evolution of Merkel cell lesions, potentially arising from the entrapped follicular epithelium (outer root sheath) within the epidermal slow adapting mechanoreceptor, “Haarsheibe.”
MCC and SK as parts of the same lesion is a unique finding that has not been reported thus far, thus lending further credence to the purported common viral etiological association.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Allen PJ, Bowne WB, Jaques DP, Brennan MF, Busam K, Coit DG, et al.
Merkel cell carcinoma: Prognosis and treatment of patients from a single institution. J Clin Oncol 2005;23:2300-9.
Heath M, Jaimes N, Lemos B, Mostaghimi A, Wang LC, Peñas PF, et al.
Clinical characteristics of Merkel cell carcinoma at diagnosis in 195 patients: The AEIOU features. J Am Acad Dermatol 2008;58:375-81.
Andres C, Belloni B, Puchta U, Sander CA, Flaig MJ. Prevalence of MCPyV in Merkel cell carcinoma and non-MCC tumors. J Cutan Pathol 2010;37:28-34.
Moens U, Van Ghelue M, Johannessen M. Oncogenic potentials of the human polyomavirus regulatory proteins. Cell Mol Life Sci 2007;64:1656-78.
Houben R, Shuda M, Weinkam R, Schrama D, Feng H, Chang Y, et al.
Merkel cell polyomavirus-infected Merkel cell carcinoma cells require expression of viral T antigens. J Virol 2010;84:7064-72.
McFalls J, Okon L, Cannon S, Lee JB. Intraepidermal proliferation of Merkel cells within a seborrheic keratosis: Merkel cell carcinoma in situ
or Merkel cell hyperplasia? J Cutan Pathol 2017;44:480-5.
Murthy S Anand
No. 52, 34th Cross, 11th Main, 4th T Block, Jayanagar, Bengaluru - 560 041, Karnataka
Source of Support: None, Conflict of Interest: None
[Figure 1], [Figure 2], [Figure 3]