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Metallic implant-associated lymphoma: ALK-negative anaplastic large cell lymphoma associated with total knee replacement arthroplasty
Jai-Hyang Go
J Pathol Transl Med. 2023;57(1):75-78.   Published online January 10, 2023
DOI: https://doi.org/10.4132/jptm.2022.10.30
  • 3,171 View
  • 107 Download
  • 1 Web of Science
  • 2 Crossref
AbstractAbstract PDF
Metallic implant-associated lymphomas are extremely rare. Only seven cases have been reported in association with knee joint arthroplasty, and all tumors were large B-cell lymphomas. This report is the first case of anaplastic large cell lymphoma occurring after total knee replacement arthroplasty. An 80‑year‑old female patient was admitted because of right knee pain for 2 years. She had undergone total knee replacement arthroplasty 10 years prior. Computed tomography showed an irregular osteolytic lesion in the right lateral femoral condyle, adjacent to the metallic prosthesis. Histologic findings reveal sheets of anaplastic tumor cells that were positive for CD2, CD4, CD5, CD43, and CD30 but negative for CD3, CD20, CD15, and anaplastic lymphoma kinase. Epstein-Barr encoding region in situ hybridization was negative. Analysis of T-cell receptor γ gene rearrangement studies using BIOMED-2–based multiplex polymerase chain reaction confirmed monoclonal T cell proliferation. The woman was finally diagnosed with ALK-negative anaplastic large cell lymphoma.

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  • Primary bone diffuse large B‐cell lymphoma (PB‐DLBCL): a distinct extranodal lymphoma of germinal centre origin, with a common EZB‐like mutational profile and good prognosis
    Vanesa‐Sindi Ivanova, John Davies, Thomas Menter, Damian Wild, Anne Müller, Fatime Krasniqi, Frank Stenner, Alexandros Papachristofilou, Stefan Dirnhofer, Alexandar Tzankov
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    JBJS Case Connector.2024;[Epub]     CrossRef
Case Study
Combined Adenosquamous and Large Cell Neuroendocrine Carcinoma of the Gallbladder
Jiyoon Jung, Yang-Seok Chae, Chul Hwan Kim, Youngseok Lee, Jeong Hyeon Lee, Dong-Sik Kim, Young-Dong Yu, Joo Young Kim
J Pathol Transl Med. 2018;52(2):121-125.   Published online October 5, 2017
DOI: https://doi.org/10.4132/jptm.2017.08.20
  • 7,571 View
  • 153 Download
  • 11 Web of Science
  • 9 Crossref
AbstractAbstract PDF
Large cell neuroendocrine carcinoma (LCNEC) of the gallbladder is extremely rare and usually combined with other type of malignancy, mostly adenocarcinoma. We report an unusual case of combined adenosquamous carcinoma and LCNEC of the gallbladder in a 54-year-old woman. A radical cholecystectomy specimen revealed a 4.3×4.0 cm polypoid mass in the fundus with infiltration of adjacent liver parenchyma. Microscopically, the tumor consisted of two distinct components. Adenosquamous carcinoma was predominant and abrupt transition from adenocarcinoma to squamous cell carcinoma was observed. LCNEC showed round cells with large, vesicular nuclei, abundant mitotic figures, and occasional pseudorosette formation. The patient received adjuvant chemotherapy. However, multiple liver metastases were identified at 3-month follow-up. Metastatic nodules were composed of LCNEC and squamous cell carcinoma components. Detecting LCNEC component is important in gallbladder cancer, because the tumor may require a different chemotherapy regimen and show early metastasis and poor prognosis.

Citations

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    Man Jiang, Yijing Zhang
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    World Journal of Surgical Oncology.2019;[Epub]     CrossRef
Original Articles
Analysis of Histologic Features Suspecting Anaplastic Lymphoma Kinase (ALK)-Expressing Pulmonary Adenocarcinoma
In Ho Choi, Dong Won Kim, Sang Yun Ha, Yoon-La Choi, Hee Jeong Lee, Joungho Han
J Pathol Transl Med. 2015;49(4):310-317.   Published online June 22, 2015
DOI: https://doi.org/10.4132/jptm.2015.05.13
  • 10,480 View
  • 90 Download
  • 18 Web of Science
  • 19 Crossref
AbstractAbstract PDF
Background
Since 2007 when anaplastic lymphoma kinase (ALK) rearrangements were discovered in non-small cell lung cancer, the ALK gene has received attention due to ALK-targeted therapy, and a notable treatment advantage has been observed in patients harboring the EML4/ALK translocation. However, using ALK-fluorescence in situ hybridization (FISH) as the standard method has demerits such as high cost, a time-consuming process, dependency on interpretation skill, and tissue preparation. We analyzed the histologic findings which could complement the limitation of ALK-FISH test for pulmonary adenocarcinoma. Methods: Two hundred five cases of ALK-positive and 101 of ALK-negative pulmonary adenocarcinoma from January 2007 to May 2013 were enrolled in this study. The histologic findings and ALK immunohistochemistry results were reviewed and compared with the results of ALK-FISH and EGFR/KRAS mutation status. Results: Acinar, cribriform, and solid growth patterns, extracellular and intracellular mucin production, and presence of signet-ring-cell element, and psammoma body were significantly more often present in ALK-positive cancer. In addition, the presence of goblet cell-like cells and presence of nuclear inclusion and groove resembling papillary thyroid carcinoma were common in the ALK-positive group. Conclusions: The above histologic parameters can be helpful in predicting ALK rearranged pulmonary adenocarcinoma, leading to rapid FISH analysis and timely treatment.

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Morphologic Analysis of Pulmonary Neuroendocrine Tumors
Seung Seok Lee, Myunghee Kang, Seung Yeon Ha, Jungsuk An, Mee Sook Roh, Chang Won Ha, Jungho Han
Korean J Pathol. 2013;47(1):16-20.   Published online February 25, 2013
DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.1.16
  • 6,669 View
  • 49 Download
  • 2 Crossref
AbstractAbstract PDF
Background

Few studies on how to diagnose pulmonary neuroendocrine tumors through morphometric analysis have been reported. In this study, we measured and analyzed the characteristic parameters of pulmonary neuroendocrine tumors using an image analyzer to aid in diagnosis.

Methods

Sixteen cases of typical carcinoid tumor, 5 cases of atypical carcinoid tumor, 15 cases of small cell carcinoma, and 51 cases of large cell neuroendocrine carcinoma were analyzed. Using an image analyzer, we measured the nuclear area, perimeter, and the major and minor axes.

Results

The mean nuclear area was 0.318±0.101 µm2 in typical carcinoid tumors, 0.326±0.119 µm2 in atypical carcinoid tumors, 0.314±0.107 µm2 in small cell carcinomas, and 0.446±0.145 µm2 in large cell neuroendocrine carcinomas. The mean nuclear circumference was 2.268±0.600 µm in typical carcinoid tumors, 2.408±0.680 µm in atypical carcinoid tumors, 2.158±0.438 µm in small cell carcinomas, and 3.247±1.276 µm in large cell neuroendocrine carcinomas. All parameters were useful in distinguishing large cell neuroendocrine carcinoma from other tumors (p=0.001) and in particular, nuclear circumference was the most effective (p=0.001).

Conclusions

Pulmonary neuroendocrine tumors showed nuclear morphology differences by subtype. Therefore, evaluation of quantitative nuclear parameters improves the accuracy and reliability of diagnosis.

Citations

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  • Clinical Significance of Persistent Tumor in Bone Marrow during Treatment of High-risk Neuroblastoma
    Young Bae Choi, Go Eun Bae, Na Hee Lee, Jung-Sun Kim, Soo Hyun Lee, Keon Hee Yoo, Ki Woong Sung, Hong Hoe Koo
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Interobserver Variability in Diagnosing High-Grade Neuroendocrine Carcinoma of the Lung and Comparing It with the Morphometric Analysis
Seung Yeon Ha, Joungho Han, Wan-Seop Kim, Byung Seong Suh, Mee Sook Roh
Korean J Pathol. 2012;46(1):42-47.   Published online February 23, 2012
DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.1.42
  • 8,215 View
  • 45 Download
  • 19 Crossref
AbstractAbstract PDF
Background

Distinguishing small cell lung carcinoma (SCLC) and large cell neuroendocrine carcinoma (LCNEC) of the lung is difficult with little information about interobserver variability.

Methods

One hundred twenty-nine cases of resected SCLC and LCNEC were independently evaluated by four pathologists and classified according to the 2004 World Health Organization criteria. Agreement was regarded as "unanimous" if all four pathologists agreed on the classification. The kappa statistic was calculated to measure the degree of agreement between pathologists. We also measured cell size using image analysis, and receiver-operating-characteristic curve analysis was performed to evaluate cell size in predicting the diagnosis of high-grade neuroendocrine (NE) carcinomas in 66 cases.

Results

Unanimous agreement was achieved in 55.0% of 129 cases. The kappa values ranged from 0.35 to 0.81. Morphometric analysis reaffirmed that there was a continuous spectrum of cell size from SCLC to LCNEC and showed that tumors with cells falling in the middle size range were difficult to categorize and lacked unanimous agreement.

Conclusions

Our results provide an objective explanation for considerable interobserver variability in the diagnosis of high-grade pulmonary NE carcinomas. Further studies would need to define more stringent and objective definitions of cytologic and architectural characteristics to reliably distinguish between SCLC and LCNEC.

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Case Report
Ovarian Large Cell Neuroendocrine Carcinoma Associated with Endocervical-like Mucinous Borderline Tumor: A Case Report and Literature Review.
Jun Mo Kim, Hyeong Chan Shin, Mi Jin Kim
Korean J Pathol. 2011;45(5):523-528.
DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.5.523
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  • 4 Crossref
AbstractAbstract PDF
Ovarian large cell neuroendocrine carcinoma is a rare tumor that is usually associated with surface epithelial tumors. Mucinous tumors are most common surface epithelial component identified in reported cases. Ovarian mucinous tumor associated with large cell neuroendocrine carcinoma is almost always an intestinal type. However, large cell neuroendocrine carcinoma associated with pure mucinous borderline tumor of endocervical-like type has not been described previously. The present case report describes a large cell neuroendocrine carcinoma associated with endocervical-like mucinous borderline tumor of the ovary in a 35-year-old woman. The tumor was confirmed by histopathology and immunohistochemistry. A review of the pertinent literature is included.

Citations

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Original Article
Distinction of Pulmonary Large Cell Neuroendocrine Carcinoma from Small Cell Lung Carcinoma Using a Panel of Bcl-2, p63, and 34betaE12.
Jun Zhe Li, Chan Choi, Yoo Duk Choi, Kook Joo Na
Korean J Pathol. 2011;45(2):170-174.
DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.2.170
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AbstractAbstract PDF
BACKGROUND
Making the distinction between large cell neuroendocrine carcinoma (LCNEC) and small cell lung carcinoma (SCLC) is difficult in some samples of biopsy tissues, but we have to separate LCNEC from SCLC because the two types of cancer may need different therapy and they have different prognostic implications. Thus far, there are no specific immunohistochemical markers that allow distinguishing these two kinds of tumors.
METHODS
We performed an immunohistochemical analysis to study the expressions of p63, Bcl-2, and 34betaE12 and to investigate whether these 3 molecules have correlations in LCNEC and SCLC. We also evaluated the expression of the neuroendocrine markers chromogranin, synaptophysin and CD56.
RESULTS
A statistical analysis was performed for p63, Bcl-2, and 34betaE12 in separate and combined panels. According to the combinations of p63, Bcl-2, and 34betaE12, there were frequent expressions of p63-/Bcl-2+ or Bcl-2+/34betaE12- in the SCLC, and there was a superior proportion of them in the SCLC rather than that in the LCNEC. The p63-/Bcl-2+ and Bcl-2+/34betaE12- antibody combinations showed higher specificities compared to any single antibody for diagnosing SCLC.
CONCLUSIONS
Bcl-2 and selective p63 or 34betaE12 made up a most useful panel of markers for making the differential diagnosis of LCNEC and SCLC.
Case Report
The Fine Needle Aspiration Cytology of a Metastatic Pulmonary Adrenocortical Carcinoma Mimicking Primary Large Cell Carcinoma of the Lung.
Na Rae Kim, Dong Hae Chung, Jae Ik Lee, Seung Yeon Ha
Korean J Pathol. 2010;44(5):558-563.
DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.5.558
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AbstractAbstract PDF
Adrenocortical carcinoma is a rare neoplasm and it has an invariably lethal prognosis. We report here on the fine needle aspiration cytologic findings of a solitary metastatic pulmonary adrenocortical carcinoma in a 24-year-old woman. The aspirate smears were very cellular and they were composed of a monomorphic population of large polyhedral cells with abundant granular or vacuolated cytoplasm, and the cells were predominantly singly scattered in a necrotic background. Multinucleated pleomorphic tumor cells were also found. Pleomorphic nuclei with thickened nuclear membranes were impinging on the cell membranes. Mitotic activity was occasionally seen. The cytologic findings of pleomorphic cells with microvacuolated cytoplasm and the presence of vague gland-like sheets, as well as the patient's history of undergoing adrenalectomy for primary adrenocortical carcinoma helped the pathologist reach the diagnosis of metastatic adrenocortical carcinoma. Here, we focus on the cytologic differential points of metastastic pulmonary adrenocortical carcinoma and primary pulmonary carcinoma, especially large cell carcinoma.
Original Articles
Large Cell Neuroendocrine Carcinoma of the Lung: Report of three cases.
Jai Hyang Go, Sun Ree Jung, Dong Hwan Shin, Woo Hee Jung
Korean J Pathol. 1995;29(4):511-516.
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AbstractAbstract PDF
We report three cases of neuroendocrine tumors of the lung characterized by large pleomorphic cell with frequent mitosis, which show neuroendocrine differentiation by both light microscopy or electron microscopy and iminunohistochemistry. These tumors have been categorized as large cell neuroendocrine carcinoma by Travis et al.(1991) in contrast with non-small cell lung cancer with neuroendocrine differentiation. In the latter, neuroendocrine differentiation is not evident by light microscopy and must be demonstrated by imunohistochemstry or by electron microscopy. The prognosis of large cell neuroendocrine carcinoma, together with non-small cell lung cancer with neuroendocrine differentiation, appears to be worse than cancer without neuroendocrine differentiation and intermediate between atypical carcinoid and small cell lung cancer. Larger numbers of patients will be needed to demonstrate significant differences in survival.
Immunohistochemical Study of Primary Large Cell Undifferentiated Carcinoma of the Lung.
Hye Seung Han, Jeong Wook Seo, Eui Keun Ham
Korean J Pathol. 1996;30(5):417-426.
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AbstractAbstract PDF
We performed a histopathologic and immunohistochemical study of 23 cases of surgically resected large cell undifferentiated carcinoma(LCUC) of the lung. The relative incidence of LCUC was 7.6% among the total resected cases of primary lung cancer over 7 years(1987-1993). The mean age of the patients was 56 years and 21 cases were male. The mean size of the mass was 5 cm and 11 cases were located peripherally. According to the histologic features, LCUC could be divided into three groups: squamous cell carcinoma-like(6 cases), adenocarcinoma-like(13 cases), and small cell carcinoma-like(4 cases) groups. The histologic differences were related to the variations of the immunohistochemical properties, but there were no differences in prognosis among these groups. Immunoreactivity to cytokeratin(CAM 5.2) was demonstrated in 22/23(96%). Carcinoembryonic antigen was positive in 13/23(57%). Neuron specific enolase and chromogranin were positive in 11/23(48%) and 5/23(22%), respectively. Vimentin was seen in 11/23(48%). From these observations, we could subclassify them by their immunologic phenotypes; exocrine features in 6/23(26%), neuroendocrine(NE) features in 4/23(17%), both exocrine and NE phenotypes in 7/23(30%), and 6 cases(26%) showed neither phenotype. The group with NE features showed a worse prognosis(P<0.05) and immunoreactivity for vimentin was also related to a worse prognosis(P<0.05). These findings imply that the immunohistochemical properties of LCUC are closely related to the histopathologic features. The groups, subdivided by histology and immunoreactivity, showed no prognostic difference except for the NE differentiation and reaction for vimentin.
Large Cell Neuroendocrine Carcinoma of the Lung 2 cases including one presented as an ovarian mass.
Yun Jung Kim, Jung Weon Shim, Hye Kyung Ahn, Young Euy Park
Korean J Pathol. 1997;31(3):257-262.
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AbstractAbstract PDF
Pulmonary tumors exhibiting neuroendocrine differentiation are classified as typical carcinoid, atypical carcinoid, and small cell lung carcinoma(SCLC). Travis et al. proposed a fourth category of large cell neuroendocrine carcinoma, which is characterized by light microscopic neuroendocrine appearance, cells of large size, polygonal shape, low nuclear cytoplasmic ratio, coarse nuclear chromatin, with prominent nucleoli high mitotic rate and frequent necrosis; and neuroendocrine features by immunohistochemistry or electron microscopy. High grade neuroendocrine carcinoma (LCAC-NE) revealed aggressive clinical course. We report two cases of neuroendocrine tumors of the lung characterized by a trabecular pattern of large pleomorphic cells with frequent mitoses and wide necrosis. The frequent metastatic sites of atypical carcinoid were liver, bone and brain. One of our case is presented, at first, as an ovarian mass, which shows multifocal rosettes and revealed metastasis from lung. Both cases expressed neuroendocrine differentiation by light microscopy and immunohistochemistry. However clinical neuroendocrine symptom were not present.
Correlation between Clinical Outcome and Proliferation Index in Diffuse Large B-Cell Lymphoma.
Sung Shin Park, Joo ryung Huh, Seung Sook Lee, Yun Koo Kang, Dae Seog Heo, Chul Woo Kim
Korean J Pathol. 1999;33(7):475-482.
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The diffuse large B-cell lymphoma category of the Revised European American Classification of Lymphoid Neoplasms (REAL) encompasses different morphologic lymphoma subtypes in a single entity, especially the diffuse large cell (DLC) and the immunoblastic (IBL) subtypes by Working Formulation (WF). The aim of this study is to determine the influence of the morphologic subdivision within this category with respect to clinical outcome and proliferative index using Ki-67 immunostainig combined with image analysis. We retrospectively reviewed 74 patients from 1990 to 1996, who were diagnosed with diffuse large B-cell lymphoma. All cases were reclassified according to REAL and Working Formulation (WF), and Ki-67 immunostaining was performed in all the cases. Fifty-eight cases (78.4%) were classified as DLC and 16 cases (21.6%) as IBL, according to WF. Twenty one cases (28.4%) showed nodal involvement and 53 cases (71.6%), extranodal involvement. All cases were found to display a variable degree of nuclear Ki-67 staining. A proliferative index of 50% or higher identified a group of patients (77%) who had poor clinical results. Overall survival was significantly reduced in these patients displaying high Ki-67 associated proliferative index compared to those with a low proliferative index (p=0.007). 5-year survival estimates were 93% in the low proliferative index group and 55% in the high proliferative index group. A multivariate regression analysis incorporating commonly used clinical prognostic factors confirmed the independent effect of proliferation index on survival. Moreover, all of the 16 IBL cases showed Ki-67 positivity of 50% or higher, which correlates with the poor clinical outcome compared to 70.7% of DLC (p=0.014). We conclude that subdivision of the diffuse large B-cell lymphoma category of the REAL classification is necessary in terms of prognostic significance in correlation with Ki-67 proliferative index.
Case Report
Effusion Cytology of Ki - 1 Positive Anaplastic Large Cell Lymphoma: A Case Report.
Mi Sook Lee, Mi Ja Lee, Yu Kyung Jeong, Sung Chul Lim, Keun Hong Kee, Ho Jong Jeon
Korean J Cytopathol. 1995;6(2):163-168.
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Ki-1 positive anaplastic large cell lymphoma is a newly described high-grade lymphoma and is defined by histopathological and immunologic criteria. We experienced a case of systemically involving Ki-1 positive anaplastic large cell lymphoma in a 44 year-old female which initially manifested as pleural effusion. Abdominopelvic CT scan showed the evidence of marked lymphadenopathy in retroperitoneal and both external and inguinal lymph nodes. On cytologic examination of pleural fluid tumor cells revealed pleomorphic large isolated cells with prominent nucleoli and abundant cytoplasms. The nuclei were large with irregular profiles including some deep invaginations. Also. occasional multilobed/multinucleated and binucleated nuclei were seen. Immunohistochemical examination was performed to differentiate from the undifferentiated adenocarcinoma. Hodgkin's disease, non-Hodgkin's lymphoma and malignant histiocytosis. The neoplastic cells were positive for leukocyte common antigen. CD3 CD30(ki-1) but negative for cytokeratin. epithelial membrane antigen. and CD15. A histologic diagnosis of Ki-1 positive anaplastic lymphoma was made by biopsies of the inguinal lymph node, polypoid lesion of the stomach and cecum.
Original Articles
Fine Needle Aspiration Cytology of Anaplastic Large Cell Lymphoma: A case mimicking malignant fibrous histiocytoma.
Jung Won Lee, Young Lyun Oh, Young Hyeh Ko
Korean J Cytopathol. 1998;9(1):99-104.
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AbstractAbstract PDF
Anaplastic large cell lymphoma(ALCL) is an uncommon type of non-Hodgkin's lymphoma(NHL) populated with anaplastic, often bizarre cells that express CD30 (Ki-1) antigen. The unusual histologic and cytologic features may cause confusion with other neoplasms, such as poorly differentiated carcinoma, melanoma, Hodgkin's disease, or true histiocytic lymphoma. Although the cytologic features of ALCL have been well described, there are few reports about cytologic findings of the sarcomatoid variant of ALCL. We experienced a case of fine needle aspiration(FNA) cytologic findings of ALCL which mimicks malignant fibrous histiocytoma. FNA cytology of chest wall mass in a 62-year-old female with a history of peripheral T-cell lymphoma(Lennert lymphoma) revealed a heterogeneous population of single cells and poorly cohesive cells with large, pleomorphic nuclei and spindle cells gathering around vascular structures within an inflammatory background. Additional features of the neoplastic cells were eccentric, multilobated nuclei with occasional "wreath-like" configuration; abundant cytoplasm with vacuolization; and prominent nucleoli. The cytologic features suggested sarcoma, especially malignant fibrous histiocytoma. The diagnosis was made retrospectively with an aid of immunocytochemical staining.
Cytomorphologic Comparison of Hodgkin Lymphoma and Anaplastic Large cell Lymphoma in Fine Needle Aspiration Cytology.
Seung Sook Lee, Jae Soo Koh, Sunhoo Park, Min Suk Kim, Soo Youn Cho, Soo Young Chung, Han Suk Ryu, Jung Soon Kim, Hwa Jung Ha, Baek Youl Ryoo
Korean J Cytopathol. 2006;17(2):126-135.
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To study the differentiating cytomorphological features of Hodgkin lymphoma (HL) and anaplastic large cell lymphoma (ALCL) using fine needle aspiration cytology (FNAC), cytomorphological features of 16 patients with HL (n=8) or ALCL (n=8) were analyzed. In the initial cytological diagnosis prior to biopsy, HLs were properly diagnosed in 4 out of 8 cases (4 HL, 2 atypical, 2 benign), whereas all ALCL were diagnosed as malignancies. However, correct diagnosis of non-Hodgkin lymphoma (NHL) was made in only two ALCL patients (2 NHL, 1 HL, 1 sarcoma, 4 malignancy without specific type). Overall, the percentage of large abnormal cells ranged from 30% to 90% in ALCL except for one case, whereas it was less than 5% in all 8 HL. A spectrum of atypical cells was more characteristic of ALCL. In contrast, HL showed an sharp difference between reactive lymphoid cells and neoplastic ones (bimorphic pattern). Moreover, the emergence of kidney-shaped abnormal cells or wreath-like multinucleated cells was helpful in diagnosing ALCL. The combination of thesefeatures would be useful in differentiating HL and ALCL. Nevertheless, these two types of lymphomas cannot be definitely distinguished based on cytomorphological features alone. Therefore, the aim of FNAC would be to suggest a specific diagnosis and indicate the need for a biopsy.

J Pathol Transl Med : Journal of Pathology and Translational Medicine
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