Thasneem Amir

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.

Mucoepidermoid thymic carcinoma: A challenging mediastinal aspirate

Primary thymic carcinoma—mucoepidermoid cell (MEC) type is rare and only one report describing the cytologic features of this neoplasm in the metastatic site is described. We describe the cytological features of poorly differentiated carcinoma possibly MEC in a 54‐year‐old man who presented with cough, weight loss, and puffiness of face for 3 months. The significance of this infrequently encountered neoplasm lies in its potential confusion of origin of the tumor—thymus or metastases from a primary bronchial MEC. Immunocytochemical profile was suggestive of a thymic carcinoma of the MEC type. Diagn. Cytopathol. 2009.

The clinical utility of combining pre-operative axillary ultrasonography and fine needle aspiration cytology with radionuclide guided sentinel lymph node biopsy in breast cancer patients with palpable axillary lymph nodes.

PURPOSE Clinically palpable lymph nodes (CPLN) are usually considered a contraindication to sentinel lymph node biopsy (SLNB) but one third of these patients are node negative. The aim of the present study is to evaluate the clinical usefulness of combining SLNB and preoperative axillary ultrasonography (AUS) with FNAC in patients with clinically palpable but indeterminate axillary lymph nodes. MATERIALS AND METHODS Fifty three patients with primary breast cancer and CPLN (mean age, 51.6 years; median age 51 years; age range, 28-73 years) were included in the study. All patients underwent AUS and fine needle aspiration (FNAC) followed by SLNB in FNAC negative patients (Group A). Patients with proven metastasis subsequently had axillary lymph node dissection (ALND) (Group B). Standard SLN scintigraphy was performed 2-4h before surgery by injecting Tc-99m labeled nano-colloid intra-dermally in the periareolar region. RESULTS Nodal metastases were documented at FNAC in 26 (49%) of the 53 patients with subsequent ALND (Group B). All 27 patients (51%) with negative FNAC results (Group A) underwent SLNB, which revealed metastasis in 6 (11%) patients. The remaining 21 (40%) patients were tumor negative and all these patients remain disease free during the follow-up period of 12-36 months with NPV of 100%. SLN was identified in all patients (100% success rate). Preoperative AUS sensitivity was 78%, specificity 76%, PPV 83%, NPV 69% and accuracy 77% (p=0.001). In comparison, ultrasound guided FNAC sensitivity, specificity, positive predictive value, negative predictive value and accuracy were 81%, 100%, 100%, 78%, 89% respectively (p=0.001). CONCLUSIONS The inaccuracy of clinical assessment allows widening of indication of SLNB. Preoperative ultrasonography and guided FNAC can help in selecting the patients suitable for ALND or SLNB. Patients who are FNAC positive can proceed to ALND whilst FNAC negative samples can undergo SLNB. This combination strategy may be helpful in avoiding unnecessary ALND.

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

A case of Langerhans' cell histiocytosis associated with Hodgkin's lymphoma: Fine-needle aspiration cytologic and histopathological features.

Langerhans cell histiocytosis (LCH) can be associated with a variety of malignant neoplasms, the most common being malignant lymphoma, especially Hodgkins lymphoma (HL). In this report, we describe the fine needle aspiration (FNA) cytologic features of a case with concurrent LCH and HL in a lymph node. A 20‐year‐old man presented with an enlarged left upper cervical lymph node. FNA smears from the swelling revealed numerous CD1a+ and S‐100+ Langerhans‐type cells (LCs) along with many eosinophils, neutrophils, and lymphocytes; there were also large atypical cells with enlarged nuclei having prominent nucleoli. The cytodiagnosis was LCH and the possibility of association with or trans‐differentiation into a lymphoma was suggested. The histopathological diagnosis of the excised left cervical lymph node was classical HL‐nodular sclerosis type (CHL‐NS) with LCH. The lacunar type Reed‐Sternberg (RS) cells were positive for CD30 and CD15, and the LCs were positive for CD1a and S‐100 protein. PET/CT imaging demonstrated hypermetabolic lymph nodes in neck, abdomen, thorax and pelvis as well as pulmonary nodules and a splenic mass. The patient received 13 courses of chemotherapy and two years later, the enhanced CT revealed regressive course of the disease. Diagn. Cytopathol. 2016;44:128–132.

T-cell-rich B-cell lymphoma (TCRBCL): limitations in fine-needle aspiration cytodiagnosis.

Exclusive reports on fine needle aspiration (FNA) cytodiagnosis of T‐cell‐rich B‐cell lymphoma (TCRBCL) are scarce in literature. This report reflects the diagnostic difficulties associated with cytodiagnosis of this rare variant of diffuse large B‐cell lymphoma. The study is based on 11 cases with age ranging from 16 to 63 years and a median of 50 years. Male to female ratio was 6:5. Ten cases presented with lymphadenopathy and one had lymphadenopathy as well as extranodal solid tumor. The initial cytodiagnosis was suggestive of TCRBCL in one case, TCRBCL/Hodgkins lymphoma (HL) in three cases, TCRBCL/HL/anaplastic large cell lymphoma (ALCL) in two cases, TCRBCL/ALCL in one case, and TCRBCL/non‐Hodgkin lymphoma (NHL) T‐cell/ALCL in one case. There was also a cytologically diagnosed HL case, which on review turned out to be HL/TCRBCL. Histopathological diagnosis was HL in all these nine cases. There were two histologically diagnosed TCRBCL cases during this period, with cytodiagnoses of NHL other than TCRBCL in one and HL in the other. While highlighting the difficulties associated with the cytodiagnosis of TCRBCL, this study conveys a word of caution that adequate immunocytochemical studies should be performed before diagnosing this rare neoplasm with a varied cytomorphology. Diagn. Cytopathol. 2012.

Metastatic nasopharyngeal carcinoma with extensive Langerhans' cell reaction and its significance: a case initially diagnosed by fine needle aspiration cytology

Langerhans’ cells (LCs) are specialised myeloidderived dendritic cells or antigen-presenting histiocytes in the body, characterised by dendritic cytoplasmic processes. It has been suggested that LCs and interdigitating reticulum cells of lymphoid tissue bind antigen–antibody complexes at the cell membrane and are involved in cell-mediated immune reaction. Studies involving the proliferation of LCs in nasopharyngeal carcinoma (NPC), which is linked to a better prognostic outcome, have rarely been reported. There are occasional published series of cases on fine needle aspiration cytology (FNAC) diagnosis of metastatic NPC, but the proliferation of LCs in cytological specimens of an NPC case has not been reported to the best of our knowledge. We describe FNAC of a case of metastatic NPC with dense infiltration of LCs, and discuss the significance of LC infiltration.

Metastatic medullary thyroid carcinoma to the breast in a patient with combined medullary and papillary carcinoma of thyroid—A case report

We report the fine‐needle aspiration cytology of a case of medullary thyroid carcinoma (MTC) metastatic to the breast in a 66‐year old female within two years of diagnosis of the thyroid tumor. The aspirate of the breast metastases revealed a plasmacytoid population of cells in loose clusters and singly with mild to moderate pleomorphism. Nuclear groves and occasional intranuclear cytoplasmic inclusions were seen. The cells stained positive for calcitonin and negative for thyroglobulin. Use of immunocytochemical methods proved useful to diagnose metastasis which was essential in planning treatment. Cases of metastatic MTC to the breast diagnosed on fine‐needle aspirates reported in the literature are reviewed. Diagn. Cytopathol. 2015;43:343–348.

Classical hodgkin lymphoma (nodular sclerosis type) associated with langerhans cell histiocytosis: a case report on fine-needle aspiration cytologic features

Langerhans cell histiocytosis (LCH) can be associated with a variety of malignant neoplasms, the most common being malignant lymphoma, especially Hodgkin lymphoma (HL). In the present report we describe the fine needle aspiration (FNA) cytologic features of a case with concurrent LCH and HL in a lymph node. A 20-year-old man presented with an enlarged left upper cervical lymph node. FNA smears from the swelling revealed numerous CD1a+ and S-100+ Langerhans histiocytes (LCs) along with many eosinophils, neutrophils, and lymphocytes; there were also large atypical cells with enlarged nuclei having prominent nucleoli. The cytodiagnosis was LCH and the possibility of association with or trans-differentiation into a lymphoma was suggested. The histopathological diagnosis of the excised lymph node was classical Hodgkin lymphoma-nodular sclerosis type (CHL-NS) with LCH. The lacunar type Reed-Sternberg (RS) cells were positive for CD30 and CD15 while the LCs were positive for CD1a and S-100 protein. PET/CT imaging of vertex to mid-thigh demonstrated hypermetabolic lymph nodes in the neck, abdomen, thorax and pelvis as well as pulmonary nodules and a splenic mass. The patient received courses of chemotherapy and two years later, the enhanced CT of neck, chest, abdomen and pelvis revealed regressive course of the disease.