“Intermediate filament buttons” in a fine‐needle aspirate of merkel cell carcinoma

A 73-year-old woman underwent fine-needle aspiration (FNA) biopsy of a painful right buttock nodule, thought to be an abscess, which had been present for six months. Eight smears, stained with rapid Romanowsky (DiffQuik) and Papanicolaou stains were interpreted by the referring pathologist as ‘‘atypical lymphoid population.’’ Additional material for cell block preparation or ancillary studies was not available. An excisional biopsy was recommended. Excision of the lesion showed a 0.7 cm dermal sheetlike infiltrate of small monotonous blue cells (Figs. C-1A and B) with scant, indistinct cytoplasm, high nuclear to cytoplasmic ratios, coarsely granular (‘‘salt-and-pepper’’) chromatin, abundant mitotic figures, and focal necrosis. The dermal nodule was separated from the normal epidermis by a ‘‘Grenz’’ zone. Flow cytometry studies (performed at the referring institution) showed an abnormal cell population lacking lymphoid and myeloid markers (CD3, CD4, CD7, CD10, CD11b, CD13, CD14, CD15, CD19, CD20, CD33, CD34, CD43, CD45, CD58, CD64, CD79a, HLA-DR, and MPO), but brightly expressing CD56 and dimly CD117. Immunostains were intensely positive for synaptophysin and weakly for chromogranin; paranuclear 3–6 lm dots stained for cytokeratins 20 (Figs. 1C and D) and AE1/AE3. Immunostains for CD3, CD20, CD34, CD45, CK7, TTF1, and melanoma-cocktail (MART-1, Melan-A and tyrosinase) were negative. Review of the rapid Romanowsky (Diff-Quik) stained FNA smears showed high cellularity with almost exclusively dissociated small blue cells. Some clumping was seen in the thicker areas of the Papanicolaou-stained smears. Closer examination revealed rare groups of 2–6 cells arranged in loosely cohesive groups, acinar configurations, or in rows. The smears showed numerous mitotic figures, pyknotic nuclei, and occasional apoptotic bodies; no significant nuclear molding, crush, or streak artifact were present. In Diff-Quik-stained smears, most neoplastic cells showed a narrow rim of light blue cytoplasm; however, some cells had slightly more abundant, eccentric, and focally vacuolated cytoplasm. Cells with intact cytoplasm measured 15–20 lm, but larger cells measuring up to 24 lm in greatest dimension were also present. Some cells were binucleated or multinucleated. Numerous naked nuclei were also present. Nuclei measured 13–17 lm were round to oval or reniform and appeared rather uniform on low power; however, at higher power, the nuclear outlines appeared more irregular, with some nuclei showing deep clefts, grooves, and polylobation. The chromatin was evenly distributed and varied from fine to coarsely granular and hyperchromatic. No nucleoli were seen. The background showed red blood cells, minimal necrotic debris, rare pale blue lymphoglandular bodies, occasional small lymphocytes, polymorphonuclear leukocytes, and tingible body macrophages. A striking cytologic feature was the presence of homogenous pink intracytoplasmic inclusions (Fig. C-2A) in Diff-Quik-stained smears. These inclusions—‘‘intermediate filament buttons’’—were identified in about 2% of intact neoplastic cells, were usually ovoid, discoid, or crescent-shaped and measured 3–7 by 2–5 lm. Most inclusions were located close to the nucleus and occasionally indented it. In cells with more ample cytoplasm, however, they were located a short distance from the nucleus, were rounded and surDepartment of Laboratory Medicine and Pathology, University of Minnesota Medical School, Minneapolis, Minnesota *Correspondence to: Stefan E. Pambuccian, MD, Professor, Department of Laboratory Medicine and Pathology, University of Minnesota Medical Center, Fairview, C422 Mayo MMC 76, 420 Delaware Street SE, Minneapolis MN 55455. E-mail: pambu001@umn.edu Received 11 April 2012; Revision 8 June 2012; Accepted 2 August 2012 DOI 10.1002/dc.22916 Published online 25 September 2012 in Wiley Online Library (wileyonlinelibrary.com).