Journal of Cytology
Home About us Ahead of print Instructions Submission Subscribe Advertise Contact e-Alerts Login 
Users Online:181
  Print this page  Email this page Small font sizeDefault font sizeIncrease font size

 Table of Contents    
Year : 2014  |  Volume : 31  |  Issue : 2  |  Page : 91-92
Syncytial variant of nodular sclerosing Hodgkin's disease: A diagnostic pitfall in fine-needle aspiration cytology

Department of Pathology, Government Medical College, Nagpur, Maharashtra, India

Click here for correspondence address and email

Date of Web Publication14-Aug-2014

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

How to cite this URL:
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 [serial online] 2014 [cited 2021 Oct 24];31:91-2. Available from:

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].
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)

Click here to view

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. 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.
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)

Click here to view

Immunoperoxidase labeling using antibodies against CD 15 and CD 30 confirmed the diagnosis of HL.

   Discussion Top

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 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.

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 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.

   References Top

1.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.  Back to cited text no. 1
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.  Back to cited text no. 2
3.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.  Back to cited text no. 3
4.Chan JK. Tumors of lymphoreticularsystem: Part A. In: Fletcher CD, editor. Diagnostic Histopathology of Tumors. 3 rd ed., Vol. 21. New York: Churchill Livingston; 2007. p. 1159-60, 1163-5.  Back to cited text no. 4
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.  Back to cited text no. 5

Correspondence Address:
Shailendra Babulalji Yadav
307, Laxmi Plaza, Koradi Road, Mankapur, Nagpur - 440 030, Maharashtra
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0970-9371.138674

Rights and Permissions


  [Figure 1], [Figure 2]

This article has been cited by
1 Linfoma de Hodgkin en enfermedad inflamatoria intestinal tratado con tiopurinas. Presentación de un caso y revisión de la literatura
Nieves Maira González,Serena Scocco,Rocío Estepa
Revista Española de Patología. 2019; 52(4): 242
[Pubmed] | [DOI]
2 Nodular sclerosis classical Hodgkin lymphoma grade 2: A diagnostic challenge to the cytopathologists
Sudha Sharma,Pranab Dey,Suvradeep Mitra,Arvind Rajwanshi,Raje Nijhawan,Radhika Srinivasan,Nalini Gupta,Ashim Das
Cancer Cytopathology. 2017; 125(2): 104
[Pubmed] | [DOI]
3 A case of the syncytial variant of classical Hodgkin lymphoma-nodular sclerosis subtype
Ryuichi YOSHINO,Kazuko OKU,Kenji SUGIO,Michiaki YAMANE,Sayumi HARA,Takayoshi GOTO,Teruaki NAGANO,Shin-ichi NAKATSUKA
The Journal of the Japanese Society of Clinical Cytology. 2016; 55(4): 245
[Pubmed] | [DOI]


    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
    Email Alert *
    Add to My List *
* Registration required (free)  

    Article Figures

 Article Access Statistics
    PDF Downloaded112    
    Comments [Add]    
    Cited by others 3    

Recommend this journal