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Paranuclear and extracellular globules in intraoperative cytology preparations of anaplastic large cell lymphoma

A 37-year-old, otherwise asymptomatic male patient with no significant medical history, presented for the evaluation of a tender, “baseball-sized” mass in the back of his right thigh. The lesion had been present for 8 years, was diagnosed clinically as an abscess and had been drained twice. The mass had grown gradually and had recently fungated through the skin, becoming tender and draining spontaneously. Examination showed local induration and draining sinuses; however, no other masses, ascending lymphangitis, cellulitis, or lymphadenopathy were noted. As the clinical differential diagnosis included an abscess, a ruptured epidermal inclusion cyst or a soft tissue tumor, surgical excision with intraoperative evaluation by frozen sections, touch imprints and scrape preparation cytology was performed The rapid Romanowsky (Diff-Quik VR ) stained smears showed abundant cellularity with single pleomorphic cells and rare cell clusters. The neoplastic cell population showed a wide variation in cell sizes. Most of the tumor cells were twice to three times the size of the surrounding red blood cells and measured 16–28 mm (mean 21 mm), but about 5% of the neoplastic cells were large pleomorphic and multinucleated, measuring up to 60 mm in greatest dimension. The tumor cells varied in shape from round to ovoid, were focally spindly or polygonal and had moderate to large amounts of slate-blue to deep blue, focally vacuolated cytoplasm, devoid of granules. The neoplastic cells had one, two or multiple round, ovoid or reniform nuclei. The nuclei measured 15–20 mm in greatest dimension and had one to five large nucleoli measuring 2–5 mm. The multinucleated cells had up to 10 nuclei of unequal size, arranged peripherally in a “horseshoe” or complete wreath pattern. In some cells the nuclei appeared polylobated, conferring the cells a flowerlike appearance. The nuclear chromatin was coarsely clumped with prominent chromatinic rims. Multiple atypical mitoses were seen. Some nuclei were either indented or displaced by large, cytoplasmic globules measuring 5– 9 mm (mean 7 mm), occasionally giving the cells a “signet-ring” appearance. These globules stained from translucent pale-pink to dark purple or magenta on Romanowsky stain, appeared homogeneous and “glassy,” and were frequently surrounded by a thin, clear halo (Fig. C1). Similar extracellular globules were also present in the background, either singly or in clusters, especially in the areas with abundant necrotic debris. The slide background also showed tingible body macrophages, apoptotic bodies, red blood cells, small round lymphocytes and occasional neutrophils. Lymphoglandular bodies were identifiable only after careful search. Similar findings were noted on the Papanicolaou stained smears, where the globules stained pale to intensely cyanophilic (Figs. C-2 and C-3). Based on the dyshesive nature of the tumor cells and their striking pleomorphism, the intraoperative cytologic and frozen section differential diagnosis was between lymphoma and malignant melanoma. A fresh tumor sample was therefore placed in RPMI and submitted for evaluation by flow cytometry. The histologic sections showed dyshesive pleomorphic neoplastic cells (Fig. C-4A). Focal intracellular, paranuclear globules were Department of Laboratory Medicine and Pathology, University of Minnesota Medical Center, Fairview, 420 Delaware Street SE, C422 Mayo MMC 76, Minneapolis, Minneapolis, 55455 *Correspondence to: Stefan Pambuccian, M.D., Loyola University Medical Center and Stritch School of Medicine, 2160 S 1st Ave, # 110– 2230, Maywood, Illinois 60153. E-mail: spambuccian@lumc.edu †Present address: Department of Pathology, Loyola University Medical Center, Maywood, IL, 2160 S. First Avenue #110, Room 2230, Maywood, Illinois, 60153 Received 15 June 2012; revised 10 December 2012; Accepted 7 February 2013 DOI: 10.1002/dc.22984 Published online 8 June 2013 in Wiley Online Library (wileyonlinelibrary.com).