Case Presentation: A 59-year-old woman with a 25-pack-year smoking history sought care after noticing a rapidly enlarging, painful, golf-ball-sized lump in her left groin. CT abdomen/pelvis showed isolated left inguinal lymphadenopathy. Ultrasound-guided biopsy revealed a poorly differentiated neuroendocrine carcinoma with a Ki-67 proliferation index near 90%. Immunohistochemistry showed AE1/3 positivity, CK20 positivity, synaptophysin positivity, chromogranin positivity, CD56 positivity, CK7 negativity, & calretinin negativity, features strongly suggestive of Merkel cell carcinoma (MCC).Repeated careful skin examinations revealed no suspicious lesions. A subtle anterior foot lesion was biopsied, showing nonspecific inflammation and no atypia. Although CK20 staining was positive, the morphology did not support MCC; hence, the lesion was considered non-diagnostic. To evaluate possible non-cutaneous primaries, she underwent PET/CT, brain MRI, upper GI endoscopy, & colonoscopy. PET/CT showed intensely increased uptake in the left subcutaneous femoral region without distant metastasis. Other studies were normal, providing both diagnostic clarity and reassurance to the patient.A multidisciplinary board, including oncology, surgery, radiation oncology, & pathology, concluded that she had Merkel cell carcinoma of unknown primary (MCC-UP) localized to regional lymph nodes. She underwent left inguinal lymph node dissection and placement of a Port-a-Cath in the right internal jugular vein. Given her high-risk features, she received adjuvant radiation to the inguinal region followed by pembrolizumab every three weeks for one year, consistent with current guidelines.She is tolerating the treatment well currently. A mild rash after her third pembrolizumab infusion resolved without intervention. She reports feeling increasingly hopeful as her labs remain stable and surveillance imaging every three months shows no recurrence.
Discussion: MCC is an uncommon but highly aggressive neuroendocrine skin cancer known for its rapid growth, early spread, & high recurrence rates [1]. The diagnosis becomes more challenging when no primary skin lesion is found, an entity known as MCC-UP, which may behave differently & may carry unique prognostic implications [2]. Accurate diagnosis requires coordination of pathology, imaging, & multidisciplinary expertise [3]. MCC-UP can be diagnostically disorienting for both clinicians and patients. Its presentation as an isolated nodal disease may reflect either regression of a primary lesion or a distinct underlying biology [2]. Accurate diagnosis depends on integrating pathology, immunohistochemistry, & comprehensive imaging [1,2]. A multidisciplinary approach is essential to ensure diagnostic confidence and coordinated care [3]. Patients with nodal MCC-UP often benefit from combined lymph node dissection, adjuvant radiation, & immunotherapy, which is now central to modern management [3]. Emerging evidence suggests MCC-UP may have outcomes comparable or even slightly better than MCC with a known primary [4], offering meaningful reassurance.
Conclusions: As a hospitalist encountering many patients with varied pathologies, MCC-UP should be considered in patients presenting with unexplained lymphadenopathy & neuroendocrine features. This case highlights the value of multidisciplinary collaboration, advanced imaging, compassionate communication, & guideline-based care when managing rare & emotionally challenging cancer diagnoses.
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