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Syncytial variant of nodular sclerosing Hodgkin’s disease: A diagnostic pitfall in fine-needle aspiration cytology Hodgkin’s lymphoma (HL) accounts for one-third of all false negative cytologic diagnosis among lymphomas.[¹] Subtyping of HL in general and nodular sclerosis Hodgkin’s disease (NSHD) in specific, based on cytologic features alone, is a matter of debate for a long time. Excessive fibrosis results in paucicellular smears and nonsampling of representative areas and errors in interpretation occur due to failure in recognition of the ‘lacunar’ cells and also misdiagnosing the syncytial variant of HL as metastatic malignancy or melanoma. Strickler et al. have reported an unusual morphologic variant of NSHD, which is not included in the Rye classification and it is termed as the syncytial variant.[2] Fine-needle aspiration cytology, of a slow growing, single, painless, firm right cervical swelling 3 cm × 3 cm, was done in a 60 years female patient. Ultrasonography and computed tomography scan of the abdomen did not reveal any lesion or malignancy. Fine-needle aspiration (FNA) smears showed abundant cellularity comprising of large cells arranged in sheets and clusters, in the background of mature lymphocytes. The cytoplasm was abundant, pale to hyaline with ill-defined margins. The nuclei were large and vesicular with prominent one or two nucleoli and cytoplasm was abundant pale to hyaline, wispy at places with abundant fibrosis and entrapped malignant cells [Figure 1]. Cytologic impression was metastasis of epithelial malignancy in lymph node. Biopsy of the cervical lymph node showed cohesive clusters and sheets of large, highly pleomorphic cells. Access this article online Quick Response Code Website: www.jcytol.org

DOI: 10.4103/0970-9371.138674

Most of these anaplastic cells showed a clear and vacuolated cytoplasm and sharply defined borders [Figure 2]. The nuclei were large, bi- and multi-nucleated and also multilobated similar to nuclei seen in the cytology smears. The nucleoli were large, prominent, one or more in number and eosinophilic to amphophilic. The cytoplasm of these cells was pale and delicate and appeared retracted in most of the cells giving the classical appearance of “lacunar cells” found in nodular sclerosis Hodgkin’s lymphoma. Because of the occurrence of prominent nucleoli these cells were considered R-S variants. Typical R-S cells were seen occasionally in the sections. Necrosis was not seen. Lymphocytes, plasma cells, and eosinophils were also seen. There was prominent absence of fibrosis and sclerosis or thick bands of collagen so essential for the diagnosis of NSHD. However, delicate collagenous material was seen deposited in between the cells [Figure 2]. Histopathologic diagnosis was kept as the HL, with a possibility of syncytial variant. Immunoperoxidase labeling using antibodies against CD 15 and CD 30 confirmed the diagnosis of HL.

Discussion Nodular sclerosing Hodgkin’s disease is characterized morphologically by microscopic nodularity because of the occurrence of interlacing bands of collagen that divide the more cellular portions of the infiltrate into discrete islands. In addition to the diagnostic nodularity, NSHD has other distinctive histologic features such as fibrosis, lacunar cells, relatively high proportion of neutrophilic inflammation including microabscesses, necrosis (often geographic) and scattered apoptotic or “mummified” R-S cells. Although, none of these features is specific for NSHD, their presence should spur the search for bands of sclerosis. However, a lesion with these features, but lacking obvious sclerosis, is named as the “cellular phase” of NSHD. However, there is little evidence to indicate a natural progression of NSHD from nonsclerotic to sclerotic phases in most cases.[3] The syncytial variant is

Meherbano M Kamal, Shubhangi R Khude, Shailendra Babulalji Yadav, Waman K Raut, Meena A Pangarkar Department of Pathology, Government Medical College, Nagpur, Maharashtra, India Address for correspondence: Dr. Shailendra Babulalji Yadav, 307, Laxmi Plaza, Koradi Road, Mankapur, Nagpur - 440 030, Maharashtra, India. E-mail: [email protected]

Journal of Cytology / April 2014 / Volume 31 / Issue 2

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Kamal, et al.: Syncytial variant of nodular sclerosing Hodgkin’s disease: A diagnostic pitfall

Inset Inset 1

Inset 2 Figure 1: Cluster of pleomorphic epithelial like cells. (Pap, ×400) Inset 1 — binuclear Reed-Sternberg cell (Pap, ×1000) Inset 2 — a cluster of R-S cell variants with delicate wispy cytoplasm (Pap, ×400)

Figure 2: Histopathology section showing vague nodularity at periphery (H and E, ×100) Inset — sheet of lacunar cells and mummified cells (H and E, ×100)

characterized by neoplastic cells forming cohesive cellular aggregates and sheets.[4] This variant may be mistaken for metastasis of carcinoma, melanoma or large cell lymphoma, often requiring immunohistochemical markers to resolve the diagnostic dilemma.

an entity along with a high index of suspicion is of utmost importance. There is evidence, though on the small number of cases, that patients with the syncytial variant of HL have more advanced disease at diagnosis.

The syncytial variant of HL, an uncommon form of NSHD, can be difficult to identify and distinguish from NHL, carcinoma, melanoma, germ cell tumor, and at times even sarcoma in FNA smears. Typical morphological appearance of lacunar cells seen in histopathology is ascribed to artifactual retraction of the delicate pale and fragile cytoplasm toward the nuclei leaving a space all around the cell, which is highlighted by a rim of lymphocytes that surrounds this space. This diagnostic feature is however an artifact of formalin fixation because it is absent in Zenker or B5-fixed tissues.[4] This feature is also not replicated in FNA smears. Therefore, the cytologic counterpart of the “lacunar cells” is difficult to identify. As it is, NSHD can only be suggested on FNA smears and biopsy is mandatory for confirmation and further typing.[5] In order to suggest a primary diagnosis of the syncytial variant of NSHD, an awareness regarding the presence of such

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Rashmi Kumari TR, Rajalakshmi T. Fine needle aspiration cytology in the diagnosis of Hodgkin’s lymphoma: Hits and misses. J Cytol 2008;25:10-2. Strickler JG, Michie SA, Warnke RA, Dorfman RF. The “Syncytial Variant” of nodular sclerosing Hodgkin’s disease. Am J Surg Pathol 1986;10:470-7. Patrick AT. The pathology of Hodgkin’s disease. In: Grossbard ML, editor. American Cancer Society Atlas of Clinical Oncology, Malignant Lymphomas. BC Decker Inc: Hamilton; 2002. p. 330-55. Chan JK. Tumors of lymphoreticularsystem: Part A. In: Fletcher CD, editor. Diagnostic Histopathology of Tumors. 3rd ed., Vol. 21. New York: Churchill Livingston; 2007. p. 1159-60, 1163-5. Das DK, Gupta SK, Datta BN, Sharma SC. Fine needle aspiration cytodiagnosis of Hodgkin’s disease and its subtypes. I. Scope and limitations. Acta Cytol 1990;34:329-36.

How to cite this article: Kamal MM, Khude SR, Yadav SB, Raut WK, Pangarkar MA. Syncytial variant of nodular sclerosing Hodgkin's disease: A diagnostic pitfall in fine-needle aspiration cytology. J Cytol 2014;31:91-2. Source of Support: Nil, Conflict of Interest: None declared.

Journal of Cytology / April 2014 / Volume 31 / Issue 2

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Syncytial variant of nodular sclerosing Hodgkin's disease: A diagnostic pitfall in fine-needle aspiration cytology.

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