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Lymph Node Metastasis With Both Components of Combined Cutaneous Squamous Cell Carcinoma/Merkel Cell (Neuroendocrine) Carcinoma

Navarrete, Jorge MD*; Gugelmeier, Natalia MD*; Mazzei, María Eugenia MD*; González, Sergio MD; Barcia, Juan J. MD; Magliano, Julio MD*

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The American Journal of Dermatopathology: August 2018 - Volume 40 - Issue 8 - p 626-628
doi: 10.1097/DAD.0000000000000927
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To the Editor:

Merkel cell carcinoma (MCC) is an infrequent primary neuroendocrine cutaneous tumor with aggressive behavior. The risk of MCC is increased 66–182-fold in organ transplant recipients and tends to appear at a younger age.1 MCC can be found in combination with other tumor types, mainly squamous cell carcinoma (SCC),2–8 and in single reports with basal cell carcinoma (BCC),9 glandular epithelial carcinomas and of sarcomatous differentiation.3,10 A biphenotypic metastasis of SSC/MCC suggests that this combination in primary tumors is higher than chance. Our work provides new evidence that supports the hypothesis that combined tumors constitute a genetically and immunohistochemically different type of tumor from MCC.4 To our knowledge, this is the first report of lymph node metastasis with both components of combined cutaneous SCC/MCC.


A 49-year-old male patient presented to our dermatology service with a history of 2 renal transplants for Alport disease in hemodialysis for the past 7 years. He was under treatment with everolimus, mofetil mycophenolate, and prednisone. He had had several surgical procedures for multiple nonmelanoma skin cancers since 2010.

On admission we observed an exophytic lesion on the lateral-external surface of his right forearm, 3 cm in diameter, round, exudative, with superficial erosion and a fibrino-hematic crust indurated on palpation (Fig. 1). The surrounding skin showed significant sun damage. Fitzpatrick phototype II. No adenopathies were palpable at the time. This asymptomatic lesion had appeared 6 months before consultation, with a progressive growth.

Exophytic lesion on the right forearm, 3 cm in diameter, round, exudative, with a superficial erosion, and a fibrino-hematic crust.

Considering the history of renal transplant and pharmacological immunosuppression, clinical diagnosis of SCC was made confirmed with an incisional punch biopsy (Fig. 2). Mohs micrographic surgery (MMS) was indicated, however, on debulking, SCC was seen as well as small monomorphic cells with vesicular nuclei (Fig. 3A). A SCC combined with MCC was suspected and confirmed with immunohistochemistry that showed positive reaction for CK20 (Fig. 3B), chromogranin, and synaptophysin in the MCC portion, as well as for CK5/6 and p63 in the SCC component.

Hematoxylin and eosin stain of incisional punch biopsy (original magnification ×4). Well differentiated SCC.
A, Hematoxylin and eosin stain of MMS debulking (original magnification ×10); well-differentiated SCC intermingled with small monomorphic basophilic cells consistent with MCC. B, Immunohistochemistry of MMS debulking (original magnification ×10); positive reaction for CK20.

A month after surgery, the patient developed an ipsilateral axillary adenopathy, which showed metastatic MCC with focal squamous differentiation (nonkeratinizing SCC) (Fig. 4A). Immunohistochemistry was positive for CK5/6 (Fig. 4B), and p63 in the squamous component, and positive for CK20 (Fig. 4C), synaptophysin and chromogranin in the MCC portion.

A, Hematoxylin and eosin stain of lymph node (original magnification ×20); metastatic MCC with nonkeratinizing SCC. Immunohistochemistry of metastatic tumor in lymph node (original magnification ×20, in similar tissue site); positive reaction for (B) CK5/6 in SCC portion and (C) CK20 in MCC portion.

Radiotherapy of the primary tumor zone and axillary zone was indicated. On follow-up, he presented bicytopenia, and bone marrow biopsy showed presence of nonhematologic cells. The patient died because of progression of his malignancy.


Classically, combined SCC/MCC has been considered as a variant of MCC. It is yet to be determined whether these 2 components derive from the same precursor cell. Combined SCC/MCC tumors are increasingly thought to represent a genetically and immunohistochemically distinct disease process from MCC.5 Although 66%–88% of the MCC are positive for Merkel cell polyomavirus (MCPyV) (with immunohistochemistry or polymerase chain reaction analysis), it is consistently negative in combined SCC/MCC.5,8,11

In our patient, without the clinically evident adenopathy on first examination, the doubt that remains is whether metastasis happened before or after MMS.

As we were able to see in our case, a common punch biopsy may only show the more superficial SCC component of a combined tumor, without evidence of MCC that is usually located deeper in dermis. This could mean a delay in diagnosis and adequate treatment. Clinically, these combined tumors are difficult to suspect; however, on dermoscopic examination, a higher frequency of polymorphous vessels and milky-red areas/globules have been described in tumors that clinically appear to be SCC or basal cell carcinoma.5 In these cases a deeper biopsy is recommended.


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