Residency Program - Case of the Month
October 2009 Final Diagnosis - Presented by Jyotsna Reddy, M.D.
Metastatic mucinous carcinoma
The tumor is composed of numerous signet ring cells in pools of mucin separated by thin strands of fibrous stroma (Figures 1-6). The cells show variably sized compressed nuclei pushed to the periphery by intracellular accumulation of pale pink mucin (Figures 1-6). Mitotic figures are absent. The tumor cells stain with mucin, CK-20, Villin, CDX-2 and are negative for CK-7 (Figures 7-11).
The patient was found to have a significant past history of poorly differentiated adenocarcinoma with signet ring cells on a biopsy from the tranverse colon and widespread peritoneal carcinomatosis with large bowel obstruction at surgery (Figures 12-13). A retroperitoneal lymph node biopsy also showed similar morphology (Figures 14-15) and immunohistochemical staining pattern including positivity for AE1/AE3, CK20, EMA, and Mucicarmine. The tumor cells are negative for CK7, Vimentin, S-100, CD68, and ER.
The clinical, morphologic and immunohistochemical (CK20+, CDX-2+, Villin+) findings are most consistent with a metastatic carcinoma from a colorectal primary. Also in the differential albeit much less likely are other gastrointestinal sites such as duodenum, stomach, esophagus and appendix, and other sites such as ovary and bladder.
Metastases to eyelids are rare and metastatic mucinous carcinoma is extremely rare. The largest published study is from the Armed Forces Institute of Pathology in 1987 with 31 patients with metastases to the eyelid with a reported female predominance (F:M = 4:1) and a median age of 60 years . Most were adenocarcinomas from breast and skin followed by gastrointestinal and genitourinary primaries [1, 2].
Metastatic lesions to the eyelids may be initially misdiagnosed as chalazion, cyst, granuloma and xanthoma [1, 2]. Grossly, they can appear as nodules, diffuse swellings or ulcerations . Microscopically, the characteristic feature is the presence of tumor cells in pools of mucin. Nuclear pleomorphism can be mild [1, 2]. Patients with eyelid metastases usually have multiple nonocular metastatic sites and the systemic prognosis is poor [2, 3].
The clues to intestinal origin of mucinous carcinoma are dirty necrosis and epithelial cells with goblet cell differentiation. Metastatic gastrointestinal carcinoma often displays a mixture of three types of mucin: sialomucins, neutral mucins, and sulfomucins . Sulfomucins distinguish carcinoma of gastrointestinal origin . Immunohistochemistry is a valuable tool in assessing the origin of the primary tumor. CDX-2 (a critical nuclear transcription factor for development of intestinal epithelium) and Villin (a cytoskeletal protein expressed in intestinal epithelial cells) are sensitive markers for gastrointestinal origin .
Differential diagnosis includes primary mucinous carcinoma of the skin, also known as mucinous adenocystic carcinoma, colloid carcinoma and mucinous eccrine adenocarcinoma (MEA) [4-6]. MEA has a predilection for eyelid and periorbital region . The origin of the tumor (eccrine versus apocrine) is somewhat controversial, but most authors favor an eccrine origin [4, 6].
MEA typically presents as a solitary slow growing lesion with a slight male predilection . Histologically, the tumor is composed of cords or nests of cuboidal epithelial cells floating in large, amorphous, PAS positive and diastase resistant mucin filled lakes [4, 6]. MEAs stain for epithelial membrane antigen (EMA), low molecular-weight cytokeratins (CK-7 and CAM 5.2), carcinoembryonic antigen (CEA), human milk factor globulins (HMFGI and II), gross cystic disease fluid protein (GCDPF 15), S-100, α-lactalbumin, TTF-1 and 3, ER, and PR [6-9]. Most mucinous sweat gland adenocarcinomas have a good prognosis [6-9]. Treatment is essentially palliative and consists of local excision or radiotherapy [6-9].
In general, metastatic tumors are more aggressive and show greater pleomorphism and higher mitotic activity. Since metastatic carcinomas from breast share a similar immunohistochemical profile to MEA, a thorough clinical workup is required to rule out a breast primary . In addition, since most colorectal cancers express CK-20, the absence of CK-20 in MEA may be helpful in clinching the diagnosis .
Rarely, an eyelid lesion may be the first sign of an occult primary and at times metastasis to the eyelids occur years after treatment of primary malignancy [1, 2, 6, and 8]. A high index of suspicion is required to make a diagnosis of malignancy in such cases.
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