Ki-1-positive anaplastic large cell lymphoma initially diagnosed as Hodgkin's disease by fine needle aspiration (FNA) cytology

A 45-year-old male presented with a large mass in the left axilla. FNA cytology was interpreted as Hodgkin's disease (HD), lymphocyte depletion (LD) type, but histopathologic and immunohistochemical examination showed features of Ki-1-positive anaplastic large cell lymphoma. Unrepresentative sampling by the FNA from the tumour periphery resulted in a false impression of dual reactive and neoplastic cell populations. which together with the frequent Reed-Sternberg-like cells led to the initial erroneous impression of HD. Therefore, the cytologic diagnosis of HD, LD should be approached with caution.     

Cytomorphology and immunocytochemistry of fine needle aspirates from blastic non-Hodgkin's lymphomas

Fine needle aspirates from 54 consecutive patients with primary or recurrent blastic (high-grade malignant) non-Hodgkin's lymphomas (NHLs) were analyzed by cytomorphology and immunocytochemistry. The cytologic diagnoses induced follicular center-cell-derived (centroblastic or anaplastic centrocytic) lymphoma (31 cases), immunoblastic lymphoma (11 cases), lymphoblastic lymphoma (9 cases) and histiocytic lymphoma (3 cases). Immunocytochemistry showed a B-cell phenotype of the neoplastic lymphocytes in all lymphoblastic lymphomas, 29 follicle center-cell lymphomas and 4 immunoblastic lymphomas. Four of the immunoblastic lymphomas were of T-cell origin while one case was not evaluable due to necrosis. A histiocytic origin was confirmed in two of the three cases that had a cytologic diagnosis of histiocytic lymphoma; the third case was shown by immunocytochemistry to be a true Ki-1-positive large cell lymphoma. Histologic and immunohistochemical analysis were performed on surgical biopsies from 18 patients. The results were in agreement with those on the fine needle aspiration (FNA) material in 14 cases. Three lymphomas could be phenotyped on aspirated material while marker studies on excised material were inconclusive. One lymph node aspirate contained mostly necrotic cells, which were unsatisfactory for adequate immunocytochemistry. However, sections from a removed tonsil from the same patient could be used for conclusive histology and phenotyping. In conclusion, the high diagnostic accuracy of combined cytomorphologic and immunocytochemical assessment of FNA samples validates the use of the technique in the diagnostic work-up of blastic (high-grade malignant) NHLs. In fact, the diagnostic accuracy seems so high that the technique can safely be used in the final diagnosis of blastic NHLs.     

Primary multilobated T-cell lymphoma of the breast diagnosed by fine needle aspiration cytology and immunocytochemistry

The fine needle aspiration (FNA) cytologic, immunocytochemical and ultrastructural findings of a primary multilobated T-cell lymphoma arising in the breast of a 61-year-old woman are described. Large pleomorphic multilobated malignant cells were primarily identified as lymphomatous in origin and phenotypically as T-cells by a selected panel of monoclonal antibodies applied to the original smears obtained by FNA biopsy. This appears to be the second report of a multilobated lymphoma arising in the breast and the first with a T-cell phenotype in this anatomic site.     

CD-30(Ki-1)-positive anaplastic large cell lymphoma in a pleural effusion. A case report with diagnosis by cytomorphologic and immunocytochemical studies.

BACKGROUND: Reports on cytodiagnosis of Ki-1-positive anaplastic large cell lymphoma (ALCL) are rare. This report describes one such case diagnosed by cytologic examination of a pleural effusion and confirmed by immunocytochemistry. CASE: An 87-year-old male presented with breathlessness, fever and a cough. Computed tomographic scan of the thorax showed a small, right, pleura-based nodule with infiltration of the immediate surroundings in addition to a massive, right-sided pleural effusion. Cytologic examination of pleural fluid revealed a heterogeneous population of cells comprising small mature lymphocytes, and numerous medium and large atypical lymphoid cells having frequent nuclear irregularity. Occasional very large cells resembling Reed-Sternberg cells or multinucleated cells with a horseshoe or wreathlike arrangement of nuclei (doughnut cells) were also present. Cytomorphology was suggestive of Ki-1 anaplastic large cell lymphoma (ALCL). Immunocytochemistry revealed intense positivity for CD-30, positivity for LCA and EMA in a variable number of cells and a negative result for cytokeratin except for occasional cells. CONCLUSION: Cytologic examination of pleural fluid can serve as a useful tool for the initial diagnosis of Ki-1-positive ALCL.     

Human embryonal epithelial cells of the developing small intestinal crypts can express the Hodgkin-cell associated antigen Ki-1 (CD30) in spontaneous abortions during the first trimester of gestation

Background  

Ki-1 (CD30) antigen expression is not found on peripheral blood cells but its expression can be induced in vitro on T and B lymphocytes by viruses and lectins. Expression of CD30 in normal tissues is very limited, being restricted mainly to a subpopulation of large lymphoid cells; in particular, cells of the recently described anaplastic large cell lymphoma (ALCL), the Reed-Sternberg (RS) cells of Hodgkin's lymphoma and scattered large parafollicular cells in normal lymphoid tissues. More recent reports have described CD30 expression in non-hematopoietic and malignant cells such as cultured human macrophages, human decidual cells, histiocytic neoplastic cells, mesothelioma cells, embryonal carcinoma and seminoma cells.     

Simultaneous flow cytometric analysis of surface markers and nuclear Ki-67 antigen in leukemia and lymphoma

The monoclonal antibody Ki-67 identifies an antigen present during the late G1, S, G2, and M phases of the cell cycle, whereas resting cells do not express this antigen. Immunostaining with Ki-67 provides a simple method with which to determine the growth fraction of a malignant cell population without requiring a laborious procedure or use of radioactive materials. Thus far, detection of Ki-67-positive cells by flow cytometry was limited because of nuclear location of the antigen. In this study, periodate-lysine-paraformaldehyde (PLP) fixation of cells in suspension, labeling with Ki-67, and the subsequent flow cytometric analysis of the tumor growth fraction is described. Fixation with PLP at -10 degrees C for 15 min rendered the plasma membrane permeable without destroying cell surface antigens. Thus double immunofluorescence studies using both a surface marker and Ki-67 could be performed. This offers the additional advantage of being able to define the phenotype of proliferating cells. This method was applied to determine the growth fraction in peripheral blood and bone marrow samples of patients with leukemia and non-Hodgkin's lymphoma. The results of Ki-67 studies in 91 patients are shown. A wide variability of individual Ki-67 values was observed within each entity. Use of this flow cytometric procedure substantially facilitates the quantification of proliferating cells in pathological blood and bone marrow samples.     

Fine needle aspiration cytology of neoplasms metastatic to the breast

The fine needle aspiration (FNA) cytologic findings in 18 cases of metastatic neoplasms of the breast are reported. The cases were encountered in a combined series of 2,529 FNA breast biopsies, of which 666 were malignant; the metastatic neoplasms of the breast thus constituted 2.7% of all the malignant breast tumors. The series consists of 15 women and 3 men, with a mean age of 48 years (range of 11 to 73 years). Sixteen biopsies confirmed metastatic malignancy in patients with known extramammary primaries; the prebiopsy clinical diagnoses in six of the patients were benign breast lesions. In eight patients, the clinical differential diagnosis was either a benign or malignant primary breast lesion versus a metastatic malignancy. In two additional patients, the FNA biopsy identified metastatic neoplasms from unsuspected extramammary primaries. The metastatic neoplasms included three small-cell carcinomas of the lung, one squamous-cell carcinoma of the lung, two malignant melanomas, three ovarian malignancies, including a dysgerminoma, and one each of carcinoma of the fallopian tube, endometrial carcinoma, transitional-cell carcinoma of the urinary bladder, prostatic carcinoma, acute granulocytic leukemia, lymphoma, mycosis fungoides, hepatoma and neuroblastoma of the retroperitoneum. Recognition of unusual cytologic patterns raised the suspicion of, or confirmed the diagnosis of, malignancy in all cases, with no false-negative diagnoses. None of the cases were cytologically interpreted as a primary breast malignancy. Ancillary studies performed on the FNA material, including immunocytochemistry, contributed to a definitive diagnosis in three cases. FNA diagnosis of metastatic malignancy of the breast is essential in order to avoid unnecessary mastectomy and to ensure appropriate chemotherapy and/or irradiation treatment.     

Grading follicular lymphoma on fine needle aspiration specimens. Comparison with proliferative index by DNA image analysis and Ki-67 labeling index

OBJECTIVE: To determine whether follicular lymphoma (FL) can be graded on fine needle aspiration (FNA) biopsies by determining the percentage of centroblasts in the neoplastic follicles on the smears. STUDY DESIGN: Eighty-nine cases of histologically confirmed cases of FL, including 31 grade 1, 46 grade 2 and 12 grade 3, were evaluated. Proliferative index (PI) by DNA image analysis (DIA) and Ki-67 labeling index (LI) were obtained on all cases. A minimum of 200 cells were counted per case (range, 200-800 cells) at 40x magnification, and the number of large cells (centroblasts) was expressed as a percentage of the total number of cells counted within the follicles. RESULTS: The percentage of centroblasts in the follicular aggregates was 9.7 +/- 2.9% in grade 1 FLs, 24.7 +/- 5.6% in grade 2 and 48.4 +/- 7.5% in grade 3. These differences were significant (P < .05). DNA image analysis of PI and Ki-67 LI differed significantly between grade 1 FLs and grade 2 and 3 FLs (P < .05), but there were no significant differences between grade 2 and 3 FLs. CONCLUSION: Determining the percentage of centroblasts in the follicular aggregates on FNA specimens is a good method of grading FLs. Using the percentage of centroblasts per follicular structure, FL grades 1, 2 and 3 were adequately distinguished. PI by DIA and Ki-67 LI clearly distinguished FL grade 1 from FL grades 2 and 3; however, it did not clearly distinguish between grades 2 and 3.     

Immunohistochemical demonstration of histone H1<Superscript>0</Superscript> in human breast carcinoma

Histone H1(0) is a linker histone subvariant present in tissues of low proliferation rate. It is supposed to participate in the expression and maintenance of the terminal differentiation phenotype. The aim of this work was to study histone H1(0) distribution in human breast carcinoma and its relationship with the processes of proliferation and differentiation. Most of the cells in carcinomas of moderate and high level of differentiation expressed histone H1(0) including cells invading connective and adipose tissues. In low differentiated tumours, the number of H1(0) expressing cells was considerably lower. Staining of myoepithelial cells, when seen, and of stromal fibroblasts was variable. The metastatic malignant cells in the lymph nodes also accumulated H1(0) but lymphocytes were always negative. All immunopositive malignant cells exhibited signs of polymorphism. Double H1(0)/Ki-67 staining showed that the growth fraction in more differentiated tumours belonged to the H1(0)-positive cells, while in poorly differentiated carcinomas it also included a cell subpopulation not expressing H1(0). If expressed, p27Kip1 was always found in H1(0)-positive cells. These findings are inconsistent with the widespread view that histone H1(0) is expressed only in terminally differentiated cells. Rather, they suggest that the protein is expressed in cells in a prolonged intermitotic period irrespective of their level of differentiation. Double H1(0)/Ki-67 immunostaining could be a useful tool in studying the growth fraction in tumours.     

Evidence for the association of the human regulatory protein Ki-1/57 with the translational machinery

Ki-1/57 is a cytoplasmic and nuclear protein of 57 kDa first identified in malignant cells from Hodgkin's lymphoma. Based on yeast-two hybrid protein interaction we found out that Ki-1/57 interacts with adaptor protein RACK1 (receptor of activated kinase 1), CIRP (cold-inducible RNA-binding protein), RPL38 (ribosomal protein L38) and FXR1 (fragile X mental retardation-related protein 1). Since these proteins are involved in the regulation of translation we suspected that Ki-1/57 may have a role in it. We show by immunoprecipitation the association of Ki-1/57 with FMRP. Confocal microscopy revealed that Ki-1/57 colocalizes with FMRP/FXR1/2 to stress granules. Furthermore Ki-1/57 cosediments with free ribosomal particles and enhances translation, when tethered to a reporter mRNA, suggesting that Ki-1/57 may be involved in translational regulation.     

Fine needle aspiration cytology of malignant spiradenoma arising in congenital eccrine spiradenoma

The fine needle aspiration (FNA) cytology of malignant eccrine spiradenoma arising in a large benign congenital eccrine spiradenoma is described. The malignant tumor was characterized by cohesive, pleomorphic cells with malignant nuclear features and numerous mitoses. FNA of the adjacent benign eccrine spiradenoma revealed prominent basement membrane deposition with an irregular tubular and nesting growth pattern and bland basaloid cells. To our knowledge, the FNA of malignant eccrine spiradenoma has not been previously described. In this case, FNA cytology was influential in directing patient management.     

Aspiration cytology, immunocytochemistry and electron microscopy of a malignant peripheral neuroectodermal tumor. A case report

The findings of fine needle aspiration (FNA) cytology, immunocytochemical staining and electron microscopy (EM) in a case of malignant peripheral neuroectodermal tumor (PNET) presenting as a soft tissue mass in the lateral abdominal wall are reported. The immediate evaluation of the aspirate revealed cells of a small round cell malignant tumor. To provide a specific preoperative diagnosis, additional cytologic material was aspirated for immunocytochemical and ultrastructural investigations. While the results of EM were nonspecific, allowing only the exclusion of other small round cell malignancies, immunocytochemical staining of the aspirate was suggestive of a PNET. The diagnosis of PNET was corroborated by histopathologic and immunohistochemical findings. This case indicates that an exact preoperative categorization of small round cell malignant tumors can be made by FNA biopsy in otherwise equivocal cases when immunocytochemical and ultrastructural techniques are also utilized.     

Negative predictive value of pulmonary fine needle aspiration cytology.

Percutaneous fine needle aspiration (FNA) for cytologic examination is an accepted and reliable technique for diagnosing neoplasia. It is less useful, however, in excluding that diagnosis. We performed a retrospective analysis of a consecutive series of pulmonary FNA specimens at Memorial Sloan-Kettering Cancer Center to determine the negative predictive value (NPV) of this technique in the setting of a large cancer hospital. Fifty-seven cases were studied. Six cases (10.5%) were initially diagnosed as negative but acellular and were not further analyzed, and another 6 were lost to follow-up; 24 cases (42.1%) were subsequently confirmed negative by tissue or clinical follow-up, and 21 of the cases (36.8%) were proven positive for malignancy by repeat aspiration, tissue diagnosis or clinical means. Of these 21 cases, 1 was misdiagnosed as negative, and review demonstrated malignant cells on the slide; 3 of the 21 cases should have been initially rejected as unsatisfactory, and 18 of the 21 contained material sufficient for a cytologic diagnosis but not representative of the lesion. On follow-up the false-negative cases showed primary adenocarcinoma, epidermoid carcinoma, lymphoma, metastatic breast carcinoma and metastatic sarcoma. Specific benign diagnoses were made on the initial cytologic preparation in three cases. No benign tumors were found. The NPV in our series was 53.3%, comparable to values in previous reports. The single largest factor contributing to false-negative diagnoses is sampling error, and we recommend repeat aspiration when no specific benign diagnosis is made. In addition, we suggest that the diagnoses of negative for malignant cells and insufficient for diagnosis or acellular be considered separate categories.     

Cytologic and immunocytologic studies of peripheral T-cell lymphomas

Lymph node aspirates from 18 peripheral T-cell lymphomas (PTLs) were analyzed. Cytologic and immunocytologic studies were performed on Cytospin preparations using the alkaline phosphatase-antialkaline phosphatase method with a panel of monoclonal antibodies (CD3, CD4, CD8, CD19 and CD30). The cytologic diagnosis was confirmed by histologic investigation. Nine lymph node aspirates from patients with Lennert's lymphoma, angioimmunoblastic (AILD)-type PTL and pleomorphic small-cell-type PTL were composed predominantly of small-to-intermediate-sized lymphocytes. An admixture of plasma cells, eosinophils, neutrophils, lymphocytes with an irregular nucleus, granula in the cytoplasm or abundant cytoplasm was also seen. Nine lymph node aspirates from patients with T-immunoblastic lymphoma, pleomorphic large-cell-type PTL and large-cell anaplastic (Ki-1+) lymphoma showed marked cytologic heterogeneity. Immunocytologic investigation of the aspirates using the antibodies CD3, CD4, CD8, CD19 and CD30 was helpful for the differentiation of PTLs from reactive lymphadenopathy and other malignant lymphomas. A strong predominance of CD3+ cells was found in only seven cases. The aspirates expressed a helper/inducer phenotype in 11 cases and a suppressor/cytotoxic phenotype in 4 cases. A T-cell phenotype not corresponding to the normal T-cell phenotype was found in nine cases. In 15 of the 18 cases, the number of CD19+ cells was found to be less than 15%. The large cells of the large-cell anaplastic (Ki-1+) lymphoma expressed the antigens CD30 and CD45 and were negative for CD15. These findings indicate that immunocytologic studies can be used in improving the cytologic diagnosis of PTLs.     

Posters. P1 A 2‐year audit of thyroid fine needle aspiration cytology

Introduction Fine needle aspiration (FNA) cytology of the thyroid is a well‐established test in the clinical work‐up of patients with solitary nodules of the thyroid. Thyroid FNA does however have limitations and audit of diagnostic performance is important. Methods The histopathology archives of the Royal Victoria Hospital were searched for all thyroid resections and the histopathological diagnosis was correlated with the pre‐operative cytological diagnosis, where available. Special emphasis was placed on the accuracy of tumour diagnosis. Results A total of 173 cases were identified during the 2‐year period, of these 93 had available pre‐operative FNA. A total of 57 tumours were identified. A small number (six of 57) of significant discrepancies were identified. These included a malignant lymphoma diagnosed as Hashimoto's thyroiditis, a metastasis which the FNA had suggested was a medullary carcinoma and an insular carcinoma diagnosed as medullary carcinoma on FNA. False positives included a colloid cyst diagnosed as suspicious of malignancy and a cytological diagnosis of papillary carcinoma not confirmed on histology. Discussion At present, the majority of thyroid FNAs in our clinics are performed by surgeons and material is not routinely available for immunocytochemistry. In spite of these limitations, there were few major discrepancies. These might be reduced if pathologist aspirators were able to perform FNAs and collect material for further studies, where necessary. This would allow identification of medullary carcinomas and malignant lymphomas. Conclusion FNA of thyroid lesions is a useful investigation in our clinical setting, however, some areas of potential for improvement have been identified.     

Fine needle aspiration cytodiagnosis of anaplastic carcinoma and malignant haemangioendothelioma of the thyroid in an endemic goitre area

Between 1970 and 1987, 20,028 fine needle aspirates (FNA) of the thyroid have been examined in the Department of Pathology of the University of Innsbruck, Austria. During this period 92 cases of anaplastic carcinoma and 16 cases of malignant haemangioendothelioma (MHE) of the thyroid were diagnosed. Forty-three out of these 108 highly malignant tumours of the thyroid underwent FNA pre-operatively (39.1%). Thirty-seven FNA contained numerous cells of a highly malignant tumour. Five specimens (11.8%) contained only necrotic material and inflammatory cells. In one case of an anaplastic carcinoma no malignant cells could be demonstrated in FNA. We conclude that pre-operative FNA of highly malignant thyroid tumours may contribute substantially to subsequent clinical management.     

Ki-67 as a prognostic marker in mantle cell lymphoma��consensus guidelines of the pathology panel of the European MCL Network

Mantle cell lymphoma (MCL) has a heterogeneous clinical course and is mainly an aggressive B cell non-Hodgkin lymphoma; however, there are some indolent cases The Ki-67 index, defined by the percentage of Ki-67-positive lymphoma cells on histopathological slides, has been shown to be a very powerful prognostic biomarker. The pathology panel of the European MCL Network evaluated methods to assess the Ki-67 index including stringent counting, digital image analysis, and estimation by eyeballing. Counting of 2 × 500 lymphoma cells is the gold standard to assess the Ki-67 index since this value has been shown to predict survival in prospective randomized trials of the European MCL Network. Estimation by eyeballing and digital image analysis showed a poor concordance with the gold standard (concordance correlation coefficients [CCC] between 0.29 and 0.61 for eyeballing and CCC of 0.24 and 0.37 for two methods of digital image analysis, respectively). Counting a reduced number of lymphoma cells (2 × 100 cells) showed high interobserver agreement (CCC = 0.74). Pitfalls of the Ki-67 index are discussed and guidelines and recommendations for assessing the Ki-67 index in MCL are given.     

Kikuchi's histiocytic necrotizing lymphadenitis. Diagnosis by fine needle aspiration

Two cases of Kikuchi's histiocytic necrotizing lymphadenitis diagnosed by fine needle aspiration (FNA) of enlarged lymph nodes are reported. The FNA smears contained randomly activated lymphoid cells, necrotic debris, karyorrhectic cells and prominent histiocytes, suggesting the presence of reactive lymph nodes. The true nature of the lesions was evident from the examination of cell block sections prepared from tissue fragments in the aspirates, which preserved the architectural relationships of the different cell types. The same patterns were found in retrospectively and subsequently examined excised lymph nodes from these cases. The differential diagnosis of this entity, which may simulate a malignant lymphoma because of the presence of large numbers of activated lymphoid cells, is discussed and the value of preparing FNA cell blocks is emphasized. Though this rare benign disease may be suspected clinically in the more typical cases, such as young women with cervical lymphadenopathy, fever, neutropenia and otherwise excellent condition, the diagnosis cannot be made without a lymph node biopsy, which FNA may be able to provide in some instances.     

Breast carcinoma with tumor giant cells. Report of a case with fine needle aspiration cytology

A 31-year-old woman presented with a cystic mass in the left breast. At fine needle aspiration (FNA), the mass felt gritty, and a firm mass remained after drainage of the cyst. Cytologic examination of the aspirate showed mononucleated malignant cells and an array of bizarre malignant multinucleated giant cells. A diagnosis of carcinoma of breast with malignant giant cells was made. Subsequent histologic study of the lesion showed a central cystic cavity lined by bizarre tumor giant cells. Immunocytochemistry and lectin cytochemistry confirmed the epithelial nature of the malignant giant cells. The entities that may yield giant cells on FNA of breast masses are discussed.     

Primary squamous cell carcinoma of the thyroid diagnosed by fine needle aspiration cytology. A report of two cases.

BACKGROUND: Primary squamous cell carcinoma of the thyroid is a rare malignant tumor that needs to be distinguished from other neoplasms. CASES: Two males aged 65 and 68 years presented with an enlarged right lobe of the thyroid. Thyroid scintigraphy revealed a cold nodule. Clinically malignancy was suspected. Fine needle aspiration (FNA) revealed numerous clusters and isolated malignant cells, dyskeratotic cells and deposits of eosinophilic granular keratin material. Subtotal thyroidectomy was performed. Histologic findings confirmed the cytologic diagnosis of squamous cell carcinoma. CONCLUSION: Primary squamous cell carcinoma of the thyroid is a rare tumor. FNA findings of this tumor were not reported before. FNA study cannot help to differentiate primary from metastatic squamous cell carcinoma of the thyroid.