A morphologic and statistical comparative study of small-cell carcinoma and non-Hodgkin's lymphoma in fine-needle aspiration biopsy material from lymph nodes

Small-cell carcinoma (SmC) and high-grade non-Hodgkin's lymphoma (NHL) are aggressive neoplasms that require prompt diagnosis and treatment. An immediate diagnosis can be obtained using fine-needle aspiration biopsy (FNAB) material from lymph nodes (LNs), which are clinically or radiologically suspicious for tumor involvement. However, in aspirates from LNs, the cytologic distinction of SmC from NHL can be challenging. The purpose of this study was to evaluate the usefulness of various cytologic features that can be used during a rapid on-site evaluation to differentiate these two entities. Twenty-seven metastatic SmC and 50 NHLs cases diagnosed by FNAB of LNs were reviewed. All NHL diagnoses (neck, 29; abdomen, 9; axilla, 6; groin, 5; and parotid, 1) were confirmed with tissue sections, flow cytometry, or immunohistochemistry. These cases were classified as follicular, 21 (42%); diffuse large B cell, 13 (26%); small lymphocytic, 7 (14%); mantle cell, 4 (8%); anaplastic large cell, 2 (4%); and 1 each (2%), Burkitt, lymphoplasmacytic, and peripheral T-cell lymphomas. Immunochemistry confirmed the cytologic diagnoses of all SmC cases (neck, 16; mediastinum, 9; abdomen, 1; and axilla, 1) with either positive chromogranin or synaptophysin. All specimens were reviewed independently by three cytopathologists who were unaware of the original diagnoses. The presence and proportion of single (noncohesive) tumor cells, lymphoglandular bodies, nuclear fragments, paranuclear blue inclusions, nuclear molding, evenly dispersed fine-granular chromatin, crush artifact, and composition of cell clusters (monomorphic vs. polymorphic) were statistically evaluated. The presence of evenly dispersed fine-granular chromatin, paranuclear blue inclusions, and nuclear fragments was each statistically significant in differentiating SmC when compared with NHL (P < 0.01). The remaining features were not significant in distinguishing SmC from NHL in LN aspirates. The identification of distinct cytologic findings such as evenly dispersed fine-granular chromatin, paranuclear blue inclusions, and nuclear fragments can be a valuable aid to accurately diagnose and differentiate metastatic SmC from NHL in FNAB preparations from LNs.     

Bilateral primary lymphoma of the breast: a case report initially diagnosed by FNAC

Primary lymphoma of the breast (PLB) is a rare disease, representing 0.04-0.5% of all malignant breast neoplasms. We present a patient with bilateral breast involvement by a high-grade diffuse large B-cell lymphoma, which was diagnosed initially by fine-needle aspiration cytology (FNAC). Mammography revealed a diffuse increase in density of the right breast and a large solitary mass on the left breast, suggestive of an inflammatory carcinoma. The patient underwent FNAC and the diagnosis of a non-Hodgkin's lymphoma (NHL) was suggested. Physical examination revealed palpable bilateral axillary lymph nodes but no evidence of concurrent widespread disease. The patient underwent complete staging evaluation. The only positive findings were an elevated lactate dehydrogenase (LDH) and evidence of axillary lymphadenopathy on CT. Excisional biopsy was performed on the left breast. The morphological and immunohistochemical analysis confirmed the diagnosis of a high-grade diffuse large B-cell lymphoma with an immunophenotype suggestive of a germinal center cell origin.     

Fine‐needle aspiration with flow cytometric immunophenotyping for primary diagnosis of intra‐abdominal lymphomas

Cytomorphology in conjunction with immunophenotypic characterization is becoming increasingly used for the primary diagnosis of non‐Hodgkin's lymphomas (NHL). This combination is especially advantageous for the diagnosis of intra‐abdominal and intrathoracic lymphomas, since unlike superficial lesions, open biopsy of deep‐seated tissues is more invasive and more costly, and is associated with a higher risk. We report the cytologic and immunophenotypic features of intra‐abdominal NHL obtained by fine‐needle aspiration (FNA). Twenty‐two cases of intra‐abdominal lesions obtained by image‐guided FNA where flow cytometry was also performed were reviewed. Of the 22 studied cases, 7 were classified as large‐cell lymphoma, 5 as follicular center‐cell lymphoma, 2 as small noncleaved‐cell lymphoma, 2 as lymphoplasmacytoid lymphoma, one as small lymphocytic lymphoma, and one as marginal‐zone lymphoma. In the remaining 4 cases where the immunophenotypic pattern was not definitive, the cytomorphologic features were of small cleaved cells in 3 cases and of mixed small cleaved and large cells in one case. We successfully classified 9 of the 10 patients on whom histologic confirmation was obtained. The successful primary classification of most intra‐abdominal non‐Hodgkin's lymphomas can be done with a combination of cytology and flow cytometry, and this can be the initial approach in patients with deep‐seated lesions. Diagn. Cytopathol. 1999;21:98–104. © 1999 Wiley‐Liss, Inc.     

Fine-needle aspiration cytology of extranodal natural killer/T-cell lymphoma

Extranodal NK/T-cell lymphoma, nasal type, is a predominantly extranodal lymphoma characterized histologically by prominent necrosis, angiocentric growth, and vascular destruction. Only one report describing its fine-needle aspiration (FNA) cytologic features is available and shows highly unusual findings for a lymphoma. The present case concerns a 58-yr-old patient that presented with a soft tissue mass of the thigh in addition to an ulcerative lesion of the palate and nodular hepatic and splenic lesions. FNA cytology of the thigh tumor was interpreted as a malignant mesenchymal lesion (sarcoma). The subsequent pathologic study revealed an NK/T-cell lymphoma. Our findings are very similar to those previously reported. They were highly unusual for a lymphoma and consisted of polymorphic, round to spindle neoplastic cells distributed in irregular aggregates, and single cells. No significant number of lymphoglandular bodies were present.     

Hodgkin's lymphoma: Diagnostic difficulties in fine‐needle aspiration cytology

It is commonly believed that cytodiagnosis of Hodgkin's lymphoma (HL) is much easier than that of non‐Hodgkin lymphoma (NHL). However, recognition of certain NHL subtypes with Reed‐Sternberg (R‐S)‐like cells and results of immunohistochemical studies point to the contrary. To study the limitations of cytology in diagnosis of HL, fine‐needle aspiration (FNA) smears of 130 lymphoma or suspected lymphoma cases were reviewed. Initial and reviewed cytodiagnoses were compared with histopathology in 89 cases. Immunocytochemical and immunohistochemical studies were performed in 56 and 59 cases, respectively. Among histologically diagnosed HL cases, definitive cytodiagnosis of HL (initial as well as reviewed) was significantly less frequent than cytodiagnosis of NHL among histologically diagnosed NHL cases (P = 0.0328 and = 0.0001, respectively). On the other hand, cytologically diagnosed HL/NHL cases were significantly more frequent in the former group (P = 0.0001 and = 0.0018, respectively). ALCL and TCRBCL were the two NHL subtypes which created confusion with HL in FNA smears. Twenty‐one cytohistological concordant HL cases and equal number of discordant cases were compared. When compared with discordant group, the patients in concordant group were significantly younger (P = 0.045). Hodgkin/Hodgkin‐like cells and typical R‐S cells were significantly more frequent in FNA smears of the concordant group (P = 0.0478 and = 0.0431, respectively). Immunocytochemical and immunohistochemical studies showed good correlation with histological diagnosis of HL. It is suggested that proper interpretation of cytologic features, together with use of immunocytochemical parameters can help in reducing the margin of error in cytodiagnois of HL. Diagn. Cytopathol. 2009. © 2009 Wiley‐Liss, Inc.     

Simultaneous medullary carcinoma of the thyroid gland and Hodgkin's lymphoma in bilateral lymph nodes of the neck: a potential pitfall in fine-needle aspiration cytology

The clinicopathological features and the cytological findings of Hodgkin's lymphoma (HL) and medullary carcinoma (MC) of the thyroid gland are described appearing simultaneously in different organs of the cervical region of the same patient. Although the cytological features of both entities are well known, the rare clinical presentation and the epithelium-like Hodgkin and Reed-Sternberg (HRS) cells of the syncytial variant of HL led to an erroneous cytological diagnosis of metastatic carcinoma of the upper aerodigestive tract.     

Fine-needle aspiration cytology and flow cytometric immunophenotyping in diagnosis and classification of non-Hodgkin lymphoma in comparison to histopathology

This prospective study aimed to compare the value of fine needle aspiration (FNA) cytology (FNAC) and flow cytometric immunophenotyping (FCI) with histopatopathology (HP) in the diagnosis and classification of non-Hodgkin lymphoma (NHL). Twenty-nine excised lymph nodes suspected of NHL were evaluated using FNAC, FCI, and HP. Specimens were divided into two equal parts; one for HP and the other for FNAC and FCI. Results were compared in terms of diagnosis (malignant, benign or reactive, and metastatic) and NHL class. With combined FNAC/FCI, 11 (37.9%) cases were diagnosed as NHL, 11 cases (37.9%) as reactive lymph node, six cases (20.6%) as Hodgkin's lymphoma, and one case (3.4%) as metastasis. HP revealed nine cases (31%) of NHL, five cases (17.2%) of reactive lymph nodes and all the diagnosed metastatic and Hodgkin's lymphoma. Considering histology as a gold standard method in diagnosis, the sensitivity, specificity, PPV and NPV of FNAC/FCI in differentiate malignant and benign lesion were 73.9%, 83.3%, 94.4%, and 45.5%, respectively and in differentiate NHL from others were 75%, 93.8%, 90%, and 83.3%, respectively. Cytology and HP in addition to FCI and HP are significantly different from determination of NHL lesions point of view (P = 0.001 and P < 0.0001, respectively). However, FCI can be considered as an adjunctive method for Cytology especially because Cytology is not competent enough to differentiate between benign lesions and Lymphoma. Additionally, FCI is shown to be an accurate method in classifying NHL.     

Two cases of primary non‐Hodgkin's lymphoma of female breast: Role of fine‐needle aspiration cytology and cell‐block immunohistochemistry

Primary breast lymphoma (PBL) is an uncommon neoplastic condition. Though HIV‐infection is a known risk factor for the development of extranodal lymphomas, mammary involvement is still a rarity. Radiologically, PBL appears as well circumscribed, heteroechoic, noncalcifying mass. Fine‐needle aspiration cytology (FNAC) is commonly used to diagnose this neoplasm; however, subcategorization requires immunophenotypic characterization of the neoplastic cells. Herein, we report two cases of PBL, including a HIV‐infected lady; in both the cases FNAC expressed features of non‐Hodgkin's lymphoma. Finally, immunohistochemistry on cell‐block with CD20 diagnosed both the cases as diffuse large B‐cell lymphoma (DLBCL). Diagn. Cytopathol. 2016;44:235–240. © 2015 Wiley Periodicals, Inc.     

Utility and outcomes of fine-needle aspiration biopsy in Hodgkin's disease

We present our 10-year experience, including clinical utilization and outcomes, with fine-needle aspiration biopsy (FNAB) in Hodgkin's disease (HD). Eighty-six cases from 68 patients with HD that were evaluated by FNAB were identified over a 10-year period. Medical records of these 68 patients were reviewed. Thirty-seven patients with primary HD underwent 41 aspirates. A diagnosis of HD was yielded in 12 and suggested in 13 cases (sensitivity 86.2%, false-positive 0%). Nine were diagnosed as atypical lymphoid cells, four as hyperplasia/other, and three as unsatisfactory. With these diagnoses, six patients began treatment without tissue exam. Thirty-five patients with suspected recurrent HD underwent 45 FNABs. Recurrent HD was confirmed in 15 and suggested in 12 aspirates (sensitivity 81.3%, false-suspicious 14.3%). With these diagnoses, 22 patients began treatment for recurrence without tissue exam. FNAB is useful both for establishing a primary diagnosis and confirming recurrence in HD and thus has a high utilization at our institution. In many instances, patients can begin therapy, negating the need for formal tissue exam.     

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/Hodgkin's 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.     

Accuracy of cytological grading of spindle-cell sarcomas

Spindle-cell sarcomas constitute an important component of soft-tissue sarcomas, where accurate grading may be more important than histologic subtype in order to plan treatment strategies and determine prognosis. To evaluate the applicability and accuracy of grading spindle-cell sarcomas on fine-needle aspiration cytology (FNAC) smears, 54 cases of histologically documented spindle-cell sarcomas, consisting of synovial sarcomas (20 cases), neurofibrosarcomas (12 cases), leiomyosarcomas (9 cases), dermatofibrosarcoma protuberans (DFSP; 6 cases), fibrosarcomas (3 cases), hemangiopericytomas (2 cases), and spindle-cell sarcomas, unclassified (2 cases), were graded according to a three-tier system proposed earlier for FNAC smears, while the histological sections were graded using the French Federation of National Cancer Centers (FNCLCC) grading system. The cytological grading was correlated with the histological grade. There was an overall cytologic and histologic concordance in 40/54 (74%) cases, and concordance in 9/13 (69%) grade I, 19/25 (76%) grade II, and 12/16 (75%) grade III cases. Analysis of grading of individual sarcomas revealed a concordance in 92% of neurofibrosarcomas, 78% of leiomyosarcomas, 70% of synovial sarcomas, 67% of dermatofibrosarcoma protuberans, 67% of fibrosarcomas, 50% of hemangiopericytomas, and 50% of cases of malignant mesenchymal tumors, spindle-cell type unclassified. Major noncorrelation was seen in 10/54 (18.5%) cases. Minor noncorrelation was seen in 4/54 (7.4%) cases. Thus it is possible to accurately predict the grade in 74% of cases of spindle-cell sarcomas. The cytological and histological concordance was better (75%) in high-grade (grades II and III) as compared to grade I sarcomas (69%). Sampling errors due to morphologic heterogeneity in sarcomas may cause noncorrelation in a few cases.     

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 Hodgkin's 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. © 2015 Wiley Periodicals, Inc.     

Molecular diagnosis of infectious diseases using cytological specimens

Pathologists have an important role in the diagnosis of infectious disease (ID). In many cases, a definitive diagnosis can be made using cytopathology alone. However, several ancillary techniques can be used on cytological material to reach a specific diagnosis by identifying the causative agent and consequently defining the management of the patient. This review aims to present the effectiveness of the application of molecular studies on cytological material to diagnose IDs and discuss the advantages and disadvantages of the various molecular techniques according to the type of cytological specimen and the infectious agents. Diagn. Cytopathol. 2016;44:156–164. © 2015 Wiley Periodicals, Inc.     

Cytodiagnosis of primary lymphoma of bone on fine-needle aspiration cytology specimens: review of 25 cases

Diagnosis of nodal lymphomas on fine-needle aspiration (FNA) cytologic specimens has been well established. However, cytodiagnosis of primary lymphoma of bone has not been well documented because of its rarity. We undertook a retrospective study of 25 cases of FNA cytologic specimens of primary lymphoma of bone. The slides were available for review in 20 cases; each case was evaluated with 15 cytologic features in conjunction with immunophenotyping and available surgical materials. Three diagnostic categories were assigned, including nondiagnostic (4/16%), suspicious (3/12%), and malignant (18/72%). Among the 18 malignant lymphoma, all were diagnosed on the basis of cytologic materials together with immunocytochemistry, except that two cases also relied on the cell blocks. The nondiagnostic and suspicious cases were subsequently confirmed to be malignant lymphoma on the surgical core biopsies. Of the 25 cases, 23 cases were large B-cell lymphoma, one follicular lymphoma large cell type, and one small lymphocytic lymphoma. False-positive or false-negative cases were not present in this study series. In conclusion, the vast majority of primary lymphoma of bone can be accurately diagnosed and classified on FNA cytologic specimens in conjunction with immunocytochemistry. The nondiagnostic and suspicious categories can be further reduced or eliminated by improving FNA techniques or by recommendation of surgical core biopsies together with other techniques such as flow cytometry and molecular analysis.     

High prevalence of hepatitis B virus infection in patients with B-cell non-Hodgkin's lymphoma in Korea

This study assessed the association of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection with non-Hodgkin's lymphoma in a highly HBV-endemic area. The prevalence of either HBV or HCV infection in 235 patients with non-Hodgkin's lymphoma was compared with that of an age- and sex-matched hospital control group of 235 patients. The prevalence of HBV infection was higher in B-cell non-Hodgkin's lymphoma (15.5%) than control (8.1%), but the prevalence of HCV infection in the non-Hodgkin's lymphoma patients (2.1%) and control group (3%) was similar. HBV prevalence increased significantly with age in the B-cell non-Hodgkin's lymphoma patients. The presence of HBV proteins and DNA in lymphoma tissues and peripheral blood mononuclear cells (PBMCs) from HBV-infected non-Hodgkin's lymphoma patients was also investigated using immunohistochemistry and PCR. HBV DNA was frequently detected in PBMCs from HBV-infected non-Hodgkin's lymphoma patients, but HBV antigens were not. Therefore, HBV infection, but not HCV infection, was associated with B-cell non-Hodgkin's lymphoma in Korea, suggesting a possible role for HBV in the development of non-Hodgkin's lymphoma.     

Thyroid low-grade B-cell lymphoma (MALT type) with extreme plasmacytic differentiation: report of a case diagnosed by fine-needle aspiration and flow cytometric study

We describe a case of thyroid marginal-zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) with extreme plasmacytic differentiation in an 80-year-old woman who had presented with a rapidly growing thyroid swelling. The diagnosis was initially suspected on fine-needle aspiration (FNA) and subsequently confirmed by flow cytometric analysis of the aspirated material. The smears revealed features of Hashimoto's thyroiditis admixed with large numbers of atypical large plasmacytoid lymphoid cells accompanied by variable numbers of small lymphocytes and mature plasma cells. The differential diagnosis of a predominantly plasmacytic smears on FNA of the thyroid is discussed herein, with emphasis on the role of immunophenotypic studies to exclude or confirm the diagnosis of lymphoma.     

Plasmablastic lymphoma involving breast: a case diagnosed by fine-needle aspiration and core needle biopsy

Plasmablastic lymphoma (PBL) is a rare lymphoma originating from B-cells with terminal differentiation. Most common anatomic site involved by PBL is the oral cavity. Involvement of other body sites has only rarely been reported. Herein, we report a rare case of EBV-negative PBL involving the breast of an HIV positive 47-year-old woman. The patient presented with decreased vision and photophobia. During physical examination, she was found to have bilateral breast masses and multiple lymphadenopathy. Fine-needle aspiration of one of the breast masses showed large malignant cells with plasmacytoid features. Immunohistochemical studies performed on the core biopsy showed that the tumor cells were positive for common leukocyte antigen CD45 and plasma cell marker CD138, but negative for the pan-B cell markers CD20 and CD79a. Molecular genetic studies showed clonal rearrangement of the immunoglobulin kappa light chain gene. This is the first case of PBL involving the breast reported in English cytological literature.     

Primary diagnosis and REAL/WHO classification of non-Hodgkin's lymphoma by fine-needle aspiration: cytomorphologic and immunophenotypic approach

The Revised European American lymphoma (REAL) and World Health Organization (WHO) classification of non-Hodgkin's lymphoma (NHL) relies on the constellation of cytologic, phenotypic, genotypic, and clinical characteristics of NHL. For the most part, the classification does not rely on architectural pattern for classification of neoplasms. This classification makes it possible to diagnose and classify lymphomas by fine-needle aspiration (FNA). In this study, we attempted to evaluate the accuracy of FNA in diagnosing and classifying NHL within the context of the REAL/WHO classifications. Cases included only those in which FNA was the primary diagnosis, followed by a surgical biopsy for confirmation. Flow cytometry (FCM) for phenotyping was carried out whenever material was available. Two groups of pathologists were identified. Group A consisted of pathologists with background training in cytopathology and/or hematopathology (three pathologists). Group B consisted of experienced surgical pathologists with no training in cytopathology and/or hematopathology (four pathologists). Seventy-four cases were included in the study. FCM phenotyping was performed in 53 cases (71%). Large cell lymphoma constituted 63% of the cases. The remaining lymphomas included Burkitt's, small lymphocytic, lymphoblastic, follicle center cell, Ki-1, mantle cell, marginal zone, and natural killer cell lymphoma. The diagnosis of lymphoma was rendered for all cases. The correct classification was seen in 63% of the cases. Classification was more accurate in immunophenotyped than in nonimmunophenotyped cases (84% vs 33%; P = 0.00004). Group A pathologists showed higher incidence of proper classification than group B (80% vs 56%; P = 0.046). The diagnosis and classification of NHL can be achieved in a large number of cases on FNA material. This accuracy can be increased if cytomorphologic criteria are established for different entities of NHL aided by FCM for phenotyping.     

Flow cytometric detection of B-clonal excess in fine needle aspirates for enhanced diagnostic accuracy in non-Hodgkin''s lymphoma in adults

Fine needle aspiration (FNA) cytology is a valuable aid to diagnosis and tumour staging in patients with non-Hodgkin's lymphoma. These tumours are often multicentric and involve sites such as the liver or the spleen which are not easily accessible to surgical biopsy. Particularly with splenic involvement, there is a diagnostic problem of morphologically distinguishing the lymphoma cells in an admixture of normal lymphocytes. Since most lymphomas in adults are of B-cell origin, we studied the diagnostic value of adding a surface immunoglobulin (sIg) light chain analysis to the cytological evaluation of FNAs. B-clonal excess was determined by flow cytometric analysis of the sIg light chain distribution and a monoclonal finding was considered diagnostic of lymphoma. In primary diagnostic procedures the light chain analysis established a diagnosis of lymphoma in 5/14 (36%) aspirates from patients with poorly differentiated tumours. Fine needle aspirates performed as part of staging procedures were morphologically normal or inconclusive in 19 cases; in seven of these (37%) lymphoma involvement was diagnosed by the light chain analysis. Diagnostic precision was enhanced by combining morphological and immunological evaluation of fine needles aspirates in patients with established or suspected non-Hodgkin's lymphoma.