Tumor-to-Tumor Metastasis of Merkel Cell Carcinoma to Warthin Tumor

Tumor-to-tumor metastasis is an uncommon phenomenon in which a primary malignancy metastasizes to a histologically distinct neoplasm.^1–3 Warthin tumor, characterized by lymphoid stroma and rich vascularity, is a recognized recipient tumor in this setting. Merkel cell carcinoma (MCC) is an aggressive cutaneous neuroendocrine carcinoma associated with Merkel cell polyomavirus infection or ultraviolet-induced mutagenesis. ⁴ Merkel cell carcinoma involving Warthin tumor is rarely reported; prior examples include Fornelli et al (2001). ⁵

A 70-year-old man presented with a nodular left cheek lesion first noted several months prior to evaluation. Biopsy established the diagnosis of Merkel cell carcinoma. Subsequent positron emission tomography and computed tomography demonstrated increased radiotracer uptake in both parotid glands and cervical lymph nodes. Biopsies of the left parotid gland and a left lateral neck lymph node confirmed Warthin tumor and nodal metastatic Merkel cell carcinoma, respectively. The patient underwent wide local excision of the primary lesion, parotidectomy, and neck dissection.

Histopathological examination of the parotidectomy specimen demonstrated a classic Warthin tumor composed of bilayered oncocytic epithelium arranged in papillary and cystic structures within a dense lymphoid stroma (Figure 1). Within the lymphoid stroma, infiltrative nests of small blue cells with high nuclear-to-cytoplasmic ratios, finely granular chromatin, and frequent mitotic figures were present. The metastatic component infiltrated the lymphoid stroma of the Warthin tumor, confirming tumor-to-tumor metastasis. The largest metastatic focus measured 9 mm. Additional findings included extranodal extension and large caliber perineural invasion. Neck dissection specimens confirmed metastatic Merkel cell carcinoma in multiple cervical lymph nodes, with the largest focus measuring 8 mm. The primary cutaneous lesion measured 1.2 cm in greatest dimension and 4.5 mm in thickness and demonstrated lymphovascular and perineural invasion.

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Figure 1.

Warthin tumor with lymphoid stroma infiltrated by Merkel cell carcinoma. (A, 10×; B, 40×; C, 10×; D, 40×, H&E stain) (A) Low-power view showing bilayered oncocytic epithelium and lymphoid stroma. (B) Interface demonstrating infiltration of Merkel cell carcinoma within the lymphoid stroma of the Warthin tumor. (C) Nests and trabeculae of small blue cells. (D) High-power view showing cells with scant cytoplasm, finely granular chromatin, and frequent mitotic figures (color online).

Immunohistochemical analysis showed strong perinuclear dot-like positivity for keratin 20 (KRT20) in the metastatic component, with synaptophysin and chromogranin expression, supporting neuroendocrine differentiation. Thyroid transcription factor-1(TTF-1) was negative. Keratin 7(RT7) highlighted the oncocytic epithelial component of the Warthin tumor and was negative in the metastatic component. This immunoprofile supported a diagnosis of Merkel cell carcinoma (Figure 2) and excluded pulmonary small cell carcinoma.

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Figure 2.

Immunohistochemical characterization of Merkel cell carcinoma and Warthin tumor. (A, 20×; B, 10×; C, 20×; D, 10×) (A) Keratin 20 shows perinuclear dot-like positivity in Merkel cell carcinoma. (B) Keratin 7 highlights the oncocytic epithelial component of the Warthin tumor, whereas the metastatic component stains negative. (C) Chromogranin shows cytoplasmic positivity in Merkel cell carcinoma. (D) Pancytokeratin highlights epithelial components.

The patient died approximately 5 months after diagnosis.

The primary diagnostic challenge is recognizing a secondary malignant population within the lymphoid stroma of a Warthin tumor.^1,3 The morphology of small blue cell tumors can mimic reactive follicular centers or the dense lymphocytic aggregates intrinsic to Warthin tumors, potentially leading to underdiagnosis of metastasis. ⁶ The differential diagnosis includes small-cell carcinoma, small-cell variant of melanoma, and various lymphomas.^7,8 The characteristic perinuclear dot-like keratin 20 staining remains the most reliable diagnostic feature for Merkel cell carcinoma, and TTF-1 negativity is essential to rule out occult lung primaries.^4,9 These findings reinforce that Warthin tumors, despite their benign nature, may serve as a reservoir for aggressive cutaneous metastases, ¹⁰ necessitating a thorough examination of the lymphoid component during routine pathological assessment.