Sanjay Jogai

Combined applications of fine needle aspiration cytology and Flow cytometric immunphenotyping for diagnosis and classification of non Hodgkin Lymphoma

Aims and objectives In this present study we have evaluated the feasibility of sub-classification of non-Hodgkins lymphoma (NHL) cases according to World Health Organizations (WHO) classification on fine needle aspiration cytology (FNAC) material along with flow cytometric immunotyping (FCI) as an adjunct. Materials and methods In this five years study, only cases suggested or confirmed as NHL by FNAC were selected and FCI was performed with a complete panel of antibodies (CD3, CD2, CD 4, CD5, CD8, CD7, CD10, CD19, CD20, CD23, CD45, κ and λ) by dual color flow cytometry. Both cytologic findings and FCI data were interpreted together to diagnose and sub-classify NHL according to WHO classification. Wherever possible the diagnoses were compared with cytology. Results There were total 48 cases included in this study. The cases were classified on FNAC as predominant small cells (12), mixed small and large cells (5) and large cells (26). In five cases a suggestion of NHL was offered on FNAC material and these cases were labeled as NHL not otherwise specified (NHL-NOS). Flow cytometry could be performed in 45 cases (93.8%) and in rest of the three cases the material was inadequate because of scanty blood mixed aspirate. Light chain restriction was demonstrated in 30 cases out of 40 cases of B-NHL (75%). There were 15 cases each of κ and λ light chain restriction in these 30 cases. With the help of combined FCI and FNAC, it was possible to sub-classify 38 cases of NHL (79%) according to WHO classification. Combined FNAC and FCI data helped to diagnose 9 cases of small lymphocytic lymphoma (SLL), 2 cases of mantle cell lymphoma (MCL), 4 cases of follicular lymphoma (FL), 17 cases of diffuse large B lymphoma (DLBL) and 6 cases of lymphoblastic lymphoma. Histopathology diagnosis was available in 31 cases of NHL out of which there were 14 recurrent and 17 cases of primary NHL. Out of 15 DLBL cases diagnosed on FCI and FNAC, histology confirmed 14 cases and one of these cases was diagnosed as Burkitts lymphoma on histology. Cases of FL (4), SLL (3) and MCL (2) were well correlated with histopathology. Out of the five cases suggestive of NHL on cytology, histopathology was available in four cases. Histology diagnosis was given as DLBL (1), SLL (1), anaplastic large cell lymphoma (1) and FL transformed into large cell NHL (1). Considering histopathology as gold standard, diagnostic specificity of combined FNAC and FCI was 100% (31/31) and sensitivity in sub-classification was 83.8% (26/31). Conclusion FNAC combined with FCI may be helpful in accurately sub-classifying NHL according to WHO classification. Many of the subtypes of NHL such as FL and MCL which were previously recognized as a pure morphologic entity can be diagnosed by combined use of FNAC and FCI. Other ancillary investigations such as chromosomal changes, cell proliferation markers etc. may be helpful in this aspect.

Follicular variant of papillary thyroid carcinoma – a cytological study

The cytological diagnosis of classical papillary carcinoma is easily established based on the characteristic architectural and nuclear features. However, the follicular variant of papillary thyroid carcinoma(FVPTC) poses a diagnostic challenge. In this study we analysed the cytological features of 14 histopathologically proven cases of FVPTC. We inferred that a combination of architectural features such as follicles and syncytial clusters and nuclear features, viz grooves, pseudoinclusions and enlarged nuclei with fine chromatin, were helpful in establishing the diagnosis. It is hence suggested that based on the combination of the aforesaid features a diagnosis of FVPTC be offered whenever it is possible. This helps in patient management, obviating the need for a second surgical intervention.

Role of fine needle aspiration cytology in nodular sclerosis variant of Hodgkin's lymphoma

OBJECTIVE To assess the efficacy of fine needle aspiration cytology (FNAC) in the diagnosis of nodular sclerosis variant of Hodgkins lymphoma (NSHL) and to analyze cytologic features that could help in subtyping a case of Hodgkins lymphoma into this variant. STUDY DESIGN FNAC smears of 18 histopathologically proven cases of NSHL were analyzed for a variety of features. RESULTS On initial cytologic assessment, 14 of 18 cases were diagnosed as Hodgkins lymphoma. No further subtyping was performed. In this retrospective analysis it was possible to revise the diagnosis in the remaining 4 cases. Of the various cytologic features analyzed, presence of numerous lacunar-type cells along with fibroblasts and collagenous material were useful pointers toward a diagnosis of nodular sclerosis variant. Fibroblasts were seen in 83.33%, collagenous material in 27.77% and numerous lacunar cells in 77.77%. CONCLUSION Subtyping of NSHL based on cytologic features alone has been a matter of debate for a long time. Of the various subtypes, nodular sclerosis poses the greatest diagnostic difficulty. Though certain cytologic features may help in suggesting a diagnosis of nodular sclerosis variant, the primary role of fine needle aspiration is to diagnose a case of Hodgkins lymphoma as such and advise histopathologic examination for further categorization.

Fine needle aspiration cytology of Hodgkin's lymphoma: A cytohistologic correlation study from a cancer center in Kuwait.

OBJECTIVE To assess the diagnostic accuracy offine needle aspiration cytology (FNAC) in the diagnosis of Hodgkins lymphoma (HL). STUDY DESIGN We selected all the cases in which a cytologic diagnosis of HL, suggestive of or suspicious for HL, or HL as the prime differential diagnosis was offered on FNAC. These cases were correlated with histopathologic follow-up. Cases of primary HL diagnosed on cytology but without histopathology were excluded from the study. RESULTS Histopathologic follow-up was available in 46 cases. Of these, 42 were correctly diagnosed as HL, and there was a discorrelation in 4 cases, comprising 3 cases of non-HL (T-cell-rich B-cell lymphoma [TCRBCL]-2, anaplastic large cell lymphoma-1) and 1 case of metastatic carcinoma. Overall accuracy was 91.3%. In 14 cases, the cytologic features were diagnostic ofrecurrence; hence, no histopathologic examination was done. No follow-up was available for the remaining 19 cases, which were excluded from the study. CONCLUSION FNAC is very useful for rapid and accurate approach to the diagnosis of recurrent and most cases of primary HL. Because of morphologic similarities, it is difficult to differentiate HL from anaplastic large cell lymphoma and TCRBCL on FNAC. It is advisable to request a histopathologic examination in all cases of primary HL.

Metaplastic mammary carcinoma with osteoclastic giant cells: a cytological mimicker of fibroadenoma

Dear Editor, We recently came across an interesting breast lesion. A 31-year-old woman presented to the cytology clinic with a 5-cm diameter lump in the upper outer quadrant of the left breast. There was a history of recent increase in size. Fine needle aspiration cytology (FNAC) was performed and reported as a fibroadenoma. Prior to this an ultrasound and a mammography were performed. Based on the report of these tests it was concluded that a malignancy could not be completely excluded. The patient underwent a lumpectomy and due to the equivocal radiological findings, a frozen section was undertaken. This was reported as a fibroepithelial tumour. On histopathological examination, the tumour was relatively well circumscribed and the predominant arrangement was in the form of a cribriform pattern. The tumour cells showed moderate nuclear pleomorphism and mitoses were infrequent. The stroma was collagenized and fresh haemorrhage as well as abundant haemosiderin-laden macrophages were also noted. In addition, many osteoclastic giant cells were seen. These contained five to 20 nuclei and were characteristically located adjacent to the tumour islands (Figure 1). The nuclei were relatively monotonous. Immunostaining showed the carcinomatous component to be positive for carcinoembryonic antigen and the giant cells stained positively for a-1-antitrypsin proving them to be of histiocytic origin. The tumour cells were negative for oestrogen and positive for progesterone receptors. The immunohistochemical staining for Her-2/neu was negative. Based on the overall features this was reported as a metaplastic mammary carcinoma with osteoclastic giant cells. We then retrieved the cytology smears and re-examined them. We observed that the smears were cellular and predominantly showed monolayered sheets of ductular epithelial cells with mild overlapping. A focal acinar arrangement was seen. The tumour cells had relatively monotonous nuclei with mild hyperchromasia. There were numerous spindle-shaped fibroblast-like cells and a few naked bipolar nuclei in the background, along with scattered osteoclastic giant cells (Figure 2). Around most foci the giant cells mingled closely with the epithelial cells. Haemosiderin-laden macrophages were also noted. Both these features were missed on initial reporting. Retrospectively, we were able to categorize this as metaplastic mammary carcinoma with osteoclastic giant cells. Mammary carcinoma with osteoclastic giant cells accounts for 0.5–1.2% of all breast carcinomas. Mammographically, these tumours have well-circumscribed margins and are usually diagnosed as fibroadenoma or cyst. Typically these are seen in the upper and outer quadrant. Grossly it is an ill-defined to well-circumscribed fleshy, dark brown tumour. Microscopic examination reveals a moderately or poorly differentiated invasive ductal carcinoma, often with a cribriform growth pattern. As the name suggests, osteoclastic giant cells are the characteristic finding. These are seen close to the edges of carcinomatous glands. It is likely that these are formed by fusion of histiocytes in the stroma. The stroma shows extravasated RBCs and haemosiderin. The diagnosis of this tumour can be suggested on FNAC based on cellular smears containing tumour cells intermixed with multinucleated giant cells. These may be confused with tumour giant cells which however have pleomorphic hyperchromatic nuclei. In the present case, on initial examination, the abundant cellularity coupled with relatively bland epithelial cells and spindled cells in the background led to the mistaken diagnosis of a fibroadenoma. The osteoclastic giant cells were missed. Clinically too, this was thought to be a fibroadenoma. It has been reported that this lesion mimics a benign tumour on cytology. The other lesions with osteoclastic giant cells include metaplastic carcinoma with cartilaginous differentiation, sarcomas with osteoclastic giant cells and Correspondence: Dr Sanjay Jogai, Kuwait Cancer Control Center, Post Box No. 42262, Shuwaikh – 70653, Kuwait. Tel.: +965 4821362; Fax: +965 4810964; E-mail: sanjayjogai@rediffmail.com

Rosai-Dorfman Disease Presenting as Bilateral Eyelid Swellings

Objective: To report a case of sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease) in an extranodal site with unusual presentation. Case Presentation: A 19-year-old girl presented with bilateral upper eyelid swellings of 2 years duration due to tumor. The masses were excised and sent for histopathological examination. Microscopic examination revealed similar features in both masses in the form of a collection of large histiocytic cells showing emperipolesis (lymphocytophagocytosis). The histiocytic cells stained positively with S-100 protein and CD68. The background comprised small lymphocytes and plasma cells. Based on the overall features a diagnosis of sinus histiocytosis with massive lymphadenopathy or Rosai-Dorfman disease was made. Conclusion: The present case highlights one of the forms in which extranodal Rosai-Dorfman disease can manifest itself. It is important to keep this differential diagnosis in mind whenever such histopathological features are encountered.

Idiopathic retroperitoneal fibrosis – a potential pitfall for fine needle aspiration cytology

Dear Editor, Idiopathic retroperitoneal fibrosis is a well recognized condition which is diagnosed combining clinical, radiological and histopathological findings. However, experience with cytological findings is limited. We herein describe a case in which fine needle aspiration was performed. A 53-year-old man presented to the cytology clinic with a clinical diagnosis of a retroperitoneal tumour (? lymphoma). Fine needle aspiration was performed under ultrasound guidance. The smears revealed scanty cellularity with few large anaplastic cells with oval to round pleomorphic nuclei and a background of activated lymphocytes, plasma cells and neutrophils (Figure 1). No Reed–Sternberg cells were seen. Although the findings were not conclusive, a possibility of anaplastic large cell or Hodgkin’s lymphoma was offered and biopsy was advised for a conclusive diagnosis. A few days later a 1 · 1 · 1 cm firm and fibrous tissue fragment was received for histopathological examination. Microscopy showed predominant bundles of dense eosinophilic collagenous tissue with scattered inflammatory infiltrate, comprising lymphocytes, plasma cells, a few eosinophils and histiocytes (Figure 2). Fibrosis infiltrated into adjacent fat. In places there were lymphoid aggregates. Inflammation was also seen in a perivascular distribution. There was no vasculitis. Based on the overall features a diagnosis of idiopathic retroperitoneal fibrosis was offered. Cytology smears were retrieved and reviewed. Cells misinterpreted as atypical cells were actually histiocytes as was confirmed on histopathological examination. In addition to the inflammatory component smears showed clumps of pink amorphous material (probably collagen) and few spindle cell fragments. Reports describing fine needle aspiration findings of idiopathic retroperitoneal fibrosis are limited. In both reports, the authors found inflammatory cells and fibrous tissue as the cytological findings. In our case, the predominant component was inflammatory and this coupled with the presence of seemingly atypical cells misled us to suggest the possibility of a

CONGENITAL PARATESTICULAR RHABDOMYOSARCOMA

A 2-month-old infant presented with right scrotal swelling that was ¢rst noticed by the parents at birth.The swelling was gradually increasing in size. On physical examination the mass could not be palpated separately from the testis. Ultrasound examination revealed a mixed echogenic mass. Serum b-human chorionic gonadotrophin (b-HCG) and alpha fetoprotein (AFP) levels were within normal limits. A high orchiectomy was performed with a di¡erential diagnosis of yolk sac tumor and a teratoma.