Case Report

A 69-year-old woman was seen postoperatively following vulvar laser ablation for a history of noninvasive Paget’s disease. She has a medical history of invasive right breast cancer status postmastectomy and adjuvant therapy. Postoperatively, she noted a new inguinal lesion. The mass was firm, 3-4 cm in size, painless, and mobile. Ultrasound scans demonstrated a well circumscribed, heterogeneous, cystic 3.7 × 3.7 × 2.1–cm mass in the right inguinal region. Color and power-Doppler scans demonstrated irregular hypervascularity. The mass localized anterior and medial to the proximal femoral vessels ( Figure 1 ) .

Ultrasound diagnosis of metastatic carcinoma

A, Conventional ultrasound scanning demonstrated a well circumscribed, heterogeneous mass with central cystic changes. B, and C, Color and power-Doppler scanning demonstrated irregular hypervascularity. The mass was localized anterior and medial to the proximal femoral vessels.

Winer. Merkel cell carcinoma with noninvasive vulvar Paget’s disease. Am J Obstet Gynecol 2012.

The differential diagnosis included metastasis from an undiagnosed vulvar carcinoma, new invasive Paget’s disease, metastatic breast cancer, or benign mass. Given the additional data that were obtained from ultrasound scanning, core and needle biopsies were deemed inappropriate, and she was taken to the operating room for excision. Intraoperatively, examination redemonstrated no suspicious vulvar or skin findings. The 4-cm mass abutted the femoral vasculature on its inferolateral aspect and the saphenous vein medially. There was no gross invasion, and the mass was excised with clear margins.

Pathologic review demonstrated small tumor cells with high nuclear/cytoplasmic ratio and finely staining, dispersed chromatin ( Figure 2 ) . By immunohistochemistry, tumor cells displayed punctate keratin staining (CAM 5.2; AE1/AE3, CK20), positive neuroendocrine markers (synaptophysin, chromogranin, CD56), and negative S-100, CD45, and TTF-1 staining. The final diagnosis was MCC.

Merkel cell carcinoma histopathologic condition

Micrograph (original magnification, ×40 objective) of hematoxylin and eosin section from A, present tumor and B, immunohistochemical stain for cytokeratin 20. Tumor cells have finely dispersed chromatin and a scant rim of cytoplasm (A) that demonstrates a dot-like pattern of stain (B) . C, A representative hematoxylin and eosin section from the patient’s previous Paget’s disease specimen is pictured. On immunohistochemistry evaluation, this specimen stained positive for cytokeratin 20 but was consistent with extra-mammary Paget’s disease.

Winer. Merkel cell carcinoma with noninvasive vulvar Paget’s disease. Am J Obstet Gynecol 2012.

A work-up for a primary lesion was completed by positron emission tomography–computed tomography with no abnormal findings. An additional, meticulous examination of all skin surfaces was performed with no findings. The patient will undergo adjuvant chemoradiation.

Comment

The incidence of MCC in the United States is approximately 1500 cases/year. Two retrospective series that have examined MCCUP have placed the incidence at approximately 12-14% of all MCC, although the authors conclude that this is likely an overestimate. Histologically, the differential diagnosis of MCC includes lymphoma, high-grade neuroendocrine carcinoma, undifferentiated carcinoma, and melanoma. Our case demonstrated the histopathologic features of MCC, which included (1) typical cytologic findings with high nuclear-cytoplasmic ratio and finely dispersed (“dusty”) chromatin and micronucleoli, (2) typical immunohistochemical findings (punctate staining pattern for keratins that included positivity for CK20 [a low molecular weight cytokeratin that rarely is expressed in carcinomas]), and (3) positivity for neuroendocrine markers. Negative stains for thyroid transcription factor 1, melanoma, and lymphoma markers further supported the diagnosis. The pathogenesis of MCCUP is unknown. Some investigators have documented regression of primary lesions; other investigators suggest the immune status of the host leads to delayed primary recognition. Other investigators hypothesize that MCCUP does not exist and that these are a primary form of MCC. Proposed MCC causes include cellular transformation secondary to sun exposure or viral infection; in addition, an association with other carcinomas is described. Our patient had 2 previous primary neoplastic processes. Breast cancer has not been associated with subsequent MCC. Squamous cell carcinoma has been associated with an approximate 13.5-fold increase in regional MCC. Our patient has a history of Paget’s disease without associated invasion or adenocarcinoma. Paget’s disease has been linked to immunomodulation and suppression. Given the location of our patient’s disease, her MCC is unlikely related to sun-exposure; therefore, one could speculate that immune suppression may have played a role in her MCC development. Treatment for MCC involves radiotherapy for local control and individualized decision regarding adjuvant chemotherapy.

Of further interest was the preoperative diagnosis of metastatic carcinoma by ultrasound scanning. Ultrasound scanning has been studied in vulvar cancer for identification of patients who require sentinel node mapping, full lymph-node dissection, or no further surgical intervention. Although this modality remains controversial, this case further suggests that ultrasound scanning could have a screening role in these patients to detect inguinal metastases preoperatively and to help to dictate the need for biopsy vs full excision and/or dissection.

In conclusion, we present the first known case of inguinal MCCUP in a patient with vulvar Paget’s disease. The clinicopathologic connection of MCC to Paget’s disease has never been elucidated; correlation with immune suppression in both entities warrants future investigation. Additionally, our report suggests that ultrasound scanning may be valuable in the evaluation of inguinal lymph nodes with suspected metastases.