Extracavitary primary effusion lymphoma presenting as a solitary brain mass.

Primary effusion lymphoma (PEL) is an uncommon B-cell lymphoma associated with human herpesvirus 8 and comprises 3-4% of all HIV-related lymphomas. It traditionally presents as a pleural, pericardial, and/or peritoneal effusion, though it can occasionally manifest as an extracavitary or solid mass in the absence of an effusion. The extracavitary or solid variant of primary effusion lymphoma has been reported in the skin, gastrointestinal tract, lung, and lymph nodes. However, very few cases have been reported in the central nervous system. We describe a case of extracavitary or solid variant of primary effusion lymphoma presenting as a brain mass in an HIV-positive man, highlighting the clinicopathologic and immunophenotypic findings of a rare entity.

Primary effusion lymphoma (PEL) is an uncommon and aggressive form of large B-cell lymphoma with a grim outlook, making up less than 1% of all lymphomas. PEL is linked to human herpesvirus 8 and predominantly impacts individuals with HIV or weakened immune systems. The typical presentation of PEL involves cancerous fluid accumulating in the chest or abdominal cavities. Occasionally, PEL can appear as a solid mass outside these cavities, termed extracavitary PEL (EC-PEL). The case we are describing highlights the difficulties in diagnosing PEL/EC-PEL. It is crucial for healthcare providers to consider EC-PEL when dealing with human herpesvirus 8-positive B-cell lymphomas, especially when patients have weakened immune systems and an unusual clinical scenario involving a solid mass, as seen in this case.

Rare diagnosis of an Epstein-Barr virus-positive extracavitary/solid variant of primary effusion lymphoma by duodenal endoscopic biopsy in a human immunodeficiency virus-seronegative and immunocompetent patient: A case report.

Primary effusion lymphoma and its tissue-based subtype extracavitary/solid variant was first described in human immunodeficiency virus (HIV)-seropositive patients. We report the case of a 50-year-old HIV-seronegative male patient who presented with icterus and cholestasis. Computed tomography revealed a 80 × 56 mm abdominal mass. Fine-needle aspiration biopsy was performed from the celiac lymph nodes and pancreatic head, under endoscopic ultrasonography guidance. A duodenal endoscopic biopsy was taken from the infiltration area, and a core biopsy was performed for the portal hilar mass. All biopsies showed similar cytohistopathological features. LCA-positive lymphoid neoplasia had a plasmacytoid/anaplastic morphology and null cell phenotype. HHV-8 and Epstein-Barr virus-encoded small RNAs (EBER) were diffuse positive. The patient, who did not have an effusion, was diagnosed with an extracavitary/solid variant of primary effusion lymphoma. Virus-associated lymphoproliferative disorders should be considered in the differential diagnosis of patients without a history of immunosuppression or HIV infection.

Outcomes in Kaposi's sarcoma-associated herpesvirus -associated primary effusion lymphoma and multicentric Castleman's disease in patients with human immunodeficiency virus (HIV) in a safety-net hospital system.

OBJECTIVE: To describe cases of Kaposi's sarcoma-associated herpesvirus (KSHV)-associated multicentric Castleman's disease (MCD) and primary effusion lymphoma (PEL) in patients with HIV from a large, safety-net hospital system in Dallas, Texas, USA. METHODS: We conducted a retrospective review of patients with HIV-associated PEL and/or MCD. RESULTS: Twelve patients with PEL and 10 patients with MCD were identified. All patients were male and 17 of 20 were men who have sex with men; 66.7% of PEL patients and 50% of MCD patients had concurrent KS at the time of diagnosis; 42% of patients with PEL and 20% of patients with MCD died during the follow-up period. We noted improved survival in our cohort compared to previous studies, particularly in our PEL patients with a median survival of 11.4 months compared to 3-6-month median survival historically. Median follow-up time for MCD patients was 17.5 months. This improved survival is despite suboptimal antiretroviral therapy (ART) adherence at diagnosis, with only 50% of patients on ART at the time of MCD/PEL diagnosis. CONCLUSION: These data highlight the importance of early recognition of PEL and MCD, and the larger-scale efforts needed to better understand the pathogenetic drivers of clinical outcomes in patients affected by KSHV-related diseases.

Primary Effusion Lymphoma, Multicentric Castleman's Disease, and Kaposi's Sarcoma in an HHV-8 and HIV-Positive Patient: A Case Report.

Primary effusion lymphoma (PEL), Kaposi's sarcoma (KS), and multicentric Castleman's disease (MCD) is an uncommon group of diseases included in the same spectrum with related characteristics. The coexistence of all of them in the same individual is a rare occurrence. We present the case of a 25-year-old patient diagnosed with human immunodeficiency virus (HIV) and the development of all these related pathologies. Despite the use of intensive treatment according to the latest recommendations, the evolution was unfavorable. This case reflects the need for new therapies and research in this field.

Primary Effusion Lymphoma in an HIV-Negative Patient with Chronic Myeloid Leukemia Treated with Dasatinib.

INTRODUCTION: Primary effusion lymphoma (PEL) is a malignant lymphomatous effusion, which by definition is Kaposi sarcoma herpesvirus/human herpesvirus 8-positive. PEL typically occurs in HIV-infected patients but can also occur in HIV-negative individuals, including in organ transplant recipients. Tyrosine kinase inhibitors (TKIs) are currently the standard of care for patients with chronic myeloid leukemia (CML), BCR::ABL1-positive. Although TKIs are extremely effective in treating CML, they alter T-cell function by inhibiting peripheral T-cell migration and altering T-cell trafficking and have been associated with the development of pleural effusions. CASE PRESENTATION: We report a case of PEL in a young, relatively immunocompetent patient with no history of organ transplant receiving dasatinib for CML, BCR::ABL1-positive. DISCUSSION: We hypothesize that the loss of T-cell function secondary to TKI therapy (dasatinib) may have resulted in the unchecked cellular proliferation of Kaposi sarcoma herpesvirus (KSHV)-infected cells, leading to the emergence of a PEL. We recommend cytologic investigation and KSHV testing in patients being treated with dasatinib for CML who present with persistent or recurrent effusions.

Primary Effusion Lymphoma-like Lymphoma Mimicking Tuberculous Pleural Effusion: Three Case Reports and a Literature Review.

Primary effusion lymphoma-like lymphoma (PEL-LL) is a rare lymphoma, localized in the body cavity without detectable tumor masses. Tuberculous pleural effusion is a form of extra pulmonary tuberculous. We herein report three cases of PEL-LL in patients with a history of pulmonary tuberculosis. Despite the presentation with lymphocyte predominance and high levels of adenosine deaminase, a notable characteristic of tuberculous pleural effusion, the patients were ultimately diagnosed with PEL-LL. Pleural fluid laboratory tests yield similar results for PEL-LL and tuberculous pleural effusion; therefore, cytological and immunophenotyping examinations are useful for their differential diagnosis and the determination of treatment.

From the archives of MD Anderson Cancer Center: Primary effusion lymphoma with simultaneous involvement of the retroperitoneum and pleural cavity.

Primary effusion lymphoma (PEL) is a rare neoplasm that arises in the context of severe immunosuppression. Acquired immunodeficiency syndrome (AIDS) as a result of human immunodeficiency virus (HIV) infection is the most common cause of immunodeficiency in patients who develop PEL. These neoplasms usually involve one or more body cavities, so-called classic PEL. The pleural cavity is most often involved, followed by the peritoneal and pericardial cavities. Involvement of the cerebrospinal fluid (CSF) and meninges is rare. A subset of patients can present with a tissue-based mass, known as the extracavitary variant. We encountered a patient with HIV infection and severe immunosuppression who presented initially with mediastinal, retroperitoneal mass and bilateral pleural effusions. He subsequently developed CSF involvement. Despite therapy, the patient relapsed with chest wall disease 6 months later and died shortly thereafter. Our literature review yielded about 400 cases of PEL reported previously. About 65 % of PEL patients have had AIDS, but a subset of patients had immunosuppression attributable to organ transplantation or physiological immunosenescence. CSF involvement has been reported in ~2 % of patients, and about 10 % of patients had both body cavity and extracavitary disease. The pathologic findings in this case were typical of extracavitary PEL. The neoplastic cells had features of plasmablasts and were positive for HHV-8, Epstein-Barr virus encoded RNA (EBER) and plasma cell associated markers, and were negative for B-cell antigens. The prognosis of patients with PEL is usually poor with a median survival less than one year in most studies. We use this patient's case as an illustration of PEL and we review the clinicopathologic findings and differential diagnosis of PEL.

Primary Effusion Lymphoma-like ATL Developing during Hemodialysis.

We herein report a patient with primary effusion lymphoma-like adult T-cell leukemia/lymphoma (PEL-like ATL) that developed during hemodialysis. A 77-year-old man developed a fever and ascites. Elevated levels of lactate dehydrogenase (LDH), calcium and soluble interleukin-2 receptor (sIL-2R) along with antibodies to human T-cell leukemia virus type 1 (HTLV-1) were seen in his blood. Lymphoma cells in ascites were positive for HTLV-1 proviral DNA, but there were no neoplastic cells in peripheral blood or bone marrow and no lymphadenopathy. He was therefore diagnosed with PEL-like ATL, acute-type. After administration of brentuximab vedotin, his serum LDH, sIL-2R and atypical cells in ascites cytology decreased. The development of novel effective molecular-targeted therapies is warranted.

Spontaneous regression of dasatinib-related primary effusion lymphoma-like lymphoma.

Primary effusion lymphoma-like lymphoma (PEL-LL) shows a unique clinical presentation, characterized by lymphomatous effusions in the body cavities. PEL-LL may be associated with hepatitis C virus infections and fluid overload states; and owing to its rarity, no standard therapies have been established. We report a case of a 55-year-old woman who developed PEL-LL during treatment with dasatinib, for chronic myeloid leukemia (CML). She presented to our hospital with dyspnea lasting for approximately a month and showed pericardial and bilateral pleural effusions. The pericardial effusion was exudative, and cytopathological and immunophenotypic examinations showed numerous CD 20-positive, large atypical lymphoid cells, which were also positive for the Epstein-Barr virus gene. No evidence of lymphadenopathy or bone marrow infiltration was found. We diagnosed PEL-LL, immediately discontinued dasatinib, and performed continuous drainage of the pericardial effusions. Complete response was achieved, and remission was maintained for 15 months. Two months after discontinuation of dasatinib, she was administered imatinib and a deep molecular response for the CML was maintained. PEL-LL occurring during dasatinib treatment is rare. We compared the results of previous reports with this case, and found that early diagnosis of PEL-LL, discontinuation of dasatinib, and sufficient drainage can improve the prognosis of PEL-LL.

Kaposi sarcoma (KS) with primary effusion lymphoma in HIV infected MSM (men having sex with men) co-infected with pulmonary tuberculosis and syphilis: a case report from India.

We describe a case of a 30-year-old MSM recently diagnosed with HIV, immunocompromised with a purplish or brown rash all over the body for 3 to 4 months. The histopathology of the cutaneous lesions and pleural effusion aspirate confirmed the diagnosis of Kaposi's sarcoma (KS) and primary effusion lymphoma (PEL). While KS is one of the AIDS-defining illnesses seen in immunocompromised patients having low CD4 count, PEL is a rare and distinct subset of AIDS-related lymphoma. Despite the widespread availability of HIV testing, HIV diagnosis gets delayed due to stigma among MSM. This case report emphasizes the importance of early suspicion for symptoms of HIV-associated opportunistic infections in high-risk populations like MSM. The report reiterates the need for an ambient stigma-free environment for improving HIV screening in this high-risk population.

Human herpesvirus 8-negative effusion-based large B-cell lymphoma: a distinct entity with unique clinicopathologic characteristics.

Rare cases of human herpesvirus 8 (HHV8)-negative effusion-based large B-cell lymphoma (EB-LBCL) occur in body cavities without antecedent or concurrent solid mass formation. In contrast to HHV8 + primary effusion lymphoma (PEL), EB-LBCL has no known association with HIV or HHV8 infection. However, the small sample sizes of case reports and series worldwide, especially from non-Japanese regions, have precluded diagnostic uniformity. Therefore, we conducted a retrospective, multi-institutional study of 55 cases of EB-LBCL and performed a comprehensive review of an additional 147 cases from the literature to identify distinct clinicopathologic characteristics. In our study, EB-LBCL primarily affected elderly (median age 80 years), immunocompetent patients and manifested as lymphomatous effusion without a solid component. The lymphomatous effusions mostly occurred in the pleural cavity (40/55, 73%), followed by the pericardial cavity (17/55, 31%). EB-LBCL expressed CD20 (53/54, 98%) and PAX5 (23/23, 100%). Most cases (30/36, 83%) were of non-germinal center B-cell subtype per the Hans algorithm. HHV8 infection was absent (0/55, 0%), while Epstein-Barr virus was detected in 6% (3/47). Clinically, some patients were managed with drainage alone (15/34, 44%), while others received rituximab alone (4/34, 12%) or chemotherapy (15/34, 44%). Eventually, 56% (22/39) died with a median overall survival (OS) of 14.9 months. Our findings were similar to those from the literature; however, compared to the non-Japanese cases, the Japanese cases had a significantly higher incidence of pericardial involvement, a higher rate of chemotherapy administration, and longer median OS. Particularly, we have found that Japanese residence, presence of pericardial effusion, and absence of MYC rearrangement are all favorable prognostic factors. Our data suggest that EB-LBCL portends a worse prognosis than previously reported, although select patients may be managed conservatively. Overall, EB-LBCL has distinct clinicopathologic characteristics, necessitating the establishment of separate diagnostic criteria and consensus nomenclature.

Synchronous visceral Kaposi sarcoma and extracavitary primary effusion lymphoma in a patient with AIDS.

While infection should always lead the differential when a patient with AIDS presents with fever, inflammatory and malignant aetiologies should also be considered. With profound immunocompromise, malignancies can develop as sequelae of viral oncogene expression. Human herpesvirus 8 (HHV-8) infection drives several AIDS-related cancers including Kaposi sarcoma (KS), multicentric Castleman disease and primary effusion lymphoma (PEL), which can present simultaneously with variable clinical features. Herein, we describe a case of synchronous visceral KS and extracavitary PEL in a patient with AIDS. The patient was treated with systemic chemotherapy and remains in remission after four cycles. We review other cases of copresenting HHV-8-related malignancies, explore the salient pathomechanisms and clinical features of these cancers and discuss treatment strategies.

Clinical Characteristics and Survival Outcomes of Primary Effusion Lymphoma: A National Cancer Database Study.

INTRODUCTION: Primary effusion lymphoma (PEL) is a rare HHV8(+) non-Hodgkin lymphoma associated with HIV infection or other causes of immunosuppression. Large-scale studies describing the natural history of this entity are lacking. MATERIALS AND METHODS: National cancer database (NCDB) was queried for patients diagnosed with PEL between 2004 and 2016. All patients age ≥ 18 years diagnosed with PEL were included. We excluded patients with multiple primary malignancies or lost follow-up. Kaplan-Meier and multivariate cox regression were used in the analyses. RESULTS: Of the 219 PEL patients included in the analysis, 179 (82%) were males, 161 (74%) Caucasian and 49 (22%) African American. Median age at diagnosis was 60 ± 19 years and median OS (mOS) was 8.5 months. One hundred and fifteen were HIV+, 63 HIV-, 111 received chemotherapy, and 101 did not. Patients who received chemotherapy had better mOS compared to patients who did not receive chemotherapy (13 vs. 3 months, P < .001). This difference was observed in HIV+ patients (22.97 vs. 1.97 months, P = .006), but not in HIV- patients (6.24 vs. 8.20 months, P = .752). On multivariate analysis, chemotherapy treatment was associated with better OS (HR 0.502 95% CI 0.324-0.777; P = .002), whereas HIV status did not affect the OS (HR 0.6 95% CI 0.3-1.4; P = .258). CONCLUSION: This largest retrospective analysis on PEL revealed that current chemotherapeutic approach is significantly beneficial for HIV+ patients but not for HIV- patients. The rapid advancement in HIV treatment might be playing a role in survival improvement among HIV+ patients. Novel therapies are needed to improve the survival of patients with PEL, especially in HIV- patients. MICROABSTRACT: PEL is a rare HHV8(+) non-Hodgkin lymphoma. Using national cancer database, we studied clinical characteristics, and outcomes of 219 PEL patients. We found that chemotherapy significantly improved overall survival in HIV+ patients. However, a similar survival improvement was not seen in HIV- patients. Significant improvement in efficacy of antiretroviral therapy is likely contributing to the survival improvement in HIV+ patients.

A Comprehensive Clinicopathologic and Molecular Study of 19 Primary Effusion Lymphomas in HIV-infected Patients.

Primary effusion lymphoma (PEL) is associated with human herpesvirus 8 and frequently with Epstein-Barr virus (EBV). We report here a single-center series of 19 human immunodeficiency virus-associated PELs, including 14 EBV+ and 5 EBV- PELs. The objectives were to describe the clinicopathologic features of PELs, with a focus on programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) expression, to search for genetic alterations by targeted deep sequencing analysis, and to compare the features between EBV+ and EBV- cases. All the patients were male, and the median age at diagnosis was 47 years old (interquartile range: 40 to 56 y). Reflecting the terminal B-cell differentiation, immunophenotypic profiles showed low expression levels of B-cell markers, including CD19 (0/19), CD20 (1/19), CD79a (0/19), PAX5 (1/19), BOB1 (3/19), and OCT2 (4/19), contrasting with a common expression of CD38 (10/19), CD138 (7/19), and IRF4/MUM1 (18/19). We observed a frequent aberrant expression of T-cell markers, especially CD3 (10/19), and less frequently CD2 (2/19), CD4 (3/19), CD5 (1/19), and CD8 (0/19). Only 2 cases were PD-L1 positive on tumor cells and none PD-1 positive. With respect to immune cells, 3 samples tested positive for PD-L1 and 5 for PD-1. Our 36-gene lymphopanel revealed 7 distinct variants in 5/10 PELs, with either a single or 2 mutations per sample: B2M (n=2), CD58 (n=1), EP300 (n=1), TNFAIP3 (n=1), ARID1A (n=1), and TP53 (n=1). Finally, we did not observe any major clinical, pathologic, or immunohistochemical differences between EBV+ and EBV- PELs and the outcome was similar (2-y overall survival probability of 61.9% [95% confidence interval, 31.2-82.1] vs. 60.0% [95% confidence interval, 12.6-88.2], respectively, P=0.62).

[Primary effusion lymphoma with multisystemic extracavitary involvement in HIV negative diagnosed by autopsy] / Linfoma primario de las efusiones con afectación extracavitaria multisistémica en HIV negativo diagnosticado mediante autopsia.

Introduction: Primary effusion lymphoma is a low-frequency and high-grade non-Hodgkin lymphoma caused by the Human Herpes virus 8. It mainly affects individuals infected with the human immunodeficiency virus (HIV), although it has also been described in HIV-negative cases. It is characterized by the presence of a malignant lymphomatous effusion in the different serous cavities, the pleural cavity being the most affected. Involvement outside the serosae is very rare. Diagnosis is made by analysis of the fluid accumulated in the serosae or by biopsy of the same, demonstrating the presence of characteristic neoplastic lymphocytes. Treatment consists of different chemotherapy regimens associated with antiretroviral therapy in HIV-positive patients. The prognosis of this disease is poor, with a survival of a few months after diagnosis. Methodology: We present the case of an 83-year-old man, HIV negative, with left pleural effusion and ascites, observing a fluid with a predominance of mononuclear cells without the presence of malignant cells on cytological examination. Results: The patient died and the autopsy made the diagnosis of Primary effusion lymphoma, also observing multisystemic extracavitary involvement. Conclusion: Although Primary effusion lymphoma preferentially affects HIV-positive individuals, the absence of HIV infection should not rule out the disease. Extracavitary involvement should be sought even in asymptomatic patients.

Introducción: El Linfoma primario de las efusiones es un Linfoma no Hodgkin de alto grado y escasa frecuencia producido por el virus Herpes Humano 8. Afecta principalmente a individuos infectados por el virus de la inmunodeficiencia humana (HIV), aunque también se ha descripto en HIV negativos. Se caracteriza por la presencia de derrame linfomatoso maligno en las distintas cavidades serosas siendo la cavidad pleural la más afectada. La afectación fuera de las serosas es muy poco frecuente. El diagnóstico se realiza por análisis del líquido acumulado en las serosas o mediante biopsia de las mismas demostrando la presencia de linfocitos neoplásicos característicos. El tratamiento consiste en distintos regímenes de quimioterapia asociados a terapia antirretroviral en pacientes HIV positivos. El pronóstico de esta enfermedad es pobre, con una supervivencia de escasos meses posteriores al diagnóstico. Metodología: Presentamos el caso de un varón de 83 años, HIV negativo, con derrame pleural izquierdo y ascitis, observándose un líquido con predominio de mononucleares sin presencia de células malignas al examen citológico. Resultados: El paciente falleció y mediante la autopsia se llegó al diagnóstico de Linfoma primario de las efusiones, observándose además afectación extracavitaria multisistémica. Conclusión: Si bien el Linfoma primario de las efusiones afecta preferentemente a individuos HIV positivos, la ausencia de infección por HIV no debe descartar la enfermedad. El compromiso extracavitario debe ser buscado aún en pacientes asintomáticos.

A rare case of indolent B cell lymphoma with massive pleural effusion as the initial presentation.

Two major type of lymphoma involve the pleura as primary neoplasms: primary effusion lymphoma (PEL) in the setting of human immunodeficiency virus (HIV) infection, and pyothorax-associated lymphomas (PAL), with a strong Epstein-Barr virus (EBV) or pyothorax association. However, indolent B cell lymphoma initially manifested as pleural effusion is an extremely rare clinical occurrence. In this study, we report a case of 52-year-old woman with no history of HIV infection or pyothorax, who only manifested long-term massive bilateral pleural effusion. This patient was characterized by lymphocytic pleural effusion, which had been misdiagnosed as tuberculous hydrothorax. A total of 75 liters of pleural effusion were drained over a two-year period. After admission to our hospital, we performed flow cytometry of pleural effusion and revealed proliferation of B lymphocytes with abnormal immune markers consistent with marginal zone B cell phenotype, although lymphocyte morphology is normal. Flow cytometry on bone marrow revealed ckappa restrictive expression on B cells further, which indicating small B cell lymphoma. The right-side pleural fluid was encapsulated after thoracoscopy and the patient's symptom were relieved. Considering the foreseeable side effects of chemotherapeutic drugs and indolent potential of the small B cell lymphoma, the patient opted not to undergo further treatment. Follow up was done 1, 3 and 6 months after discharge, the depths of bilateral pleural effusion on ultrasound stabilized around 3 cm without thoracentesis. This case is thought to be an unusual presentation because the pleural lymphoma occurred on an immunocompetent adult woman and the type was small B cell lymphoma, which were totally different from PEL or PAL. We also describe the use of flow cytometry to effectively diagnose the unexplained pleural effusion, and discuss the findings using relevant previously reported literature. Overall, our findings provide new insights to deal with unexplained pleural effusion and the value of flow cytometry in diagnosis.

Human herpesvirus-8-positive primary effusion lymphoma in HIV-negative patients: Single institution case series with a multidisciplinary characterization.

BACKGROUND: Primary effusion lymphoma (PEL) is a very rare non-Hodgkin lymphoma caused by human herpesvirus-8 (HHV8) that grows in liquid phase within body cavities. The diagnosis of PEL is based on cytology but requires confirmatory ancillary tests. PEL occurs mainly in association with HIV infection. This study describes 9 cases of PEL in HIV-negative patients and compares their characteristics with 10 HIV-associated cases of PEL diagnosed at a single institution in Italy between 1995 and 2019. METHODS: Clinical records were reviewed for demographic data, comorbidities, laboratory abnormalities, and outcome. PEL samples were evaluated for cytomorphology, immunophenotype, immunoglobulin (IG)/T cell receptor (TR) rearrangements, and HHV8 and Epstein-Barr virus (EBV) viral loads in effusion supernatants. RESULTS: HIV-unrelated PEL occurred in 8 elderly patients (7 men, 1 woman) and 1 young adult with primary antibody deficiency. Cytology revealed HHV8-positive lymphoma cells lacking B/T cell antigens and exhibiting 2 cell patterns (polymorphous or monotonous). IG was clonally rearranged in all cases; aberrant TRG occurred in 2 cases. Effusion supernatants had more than 106 HHV8 DNA copies per mL and variable loads of EBV DNA. Compared with HIV-associated PEL, the HIV-negative cohort was characterized by older age, less frequent association with Kaposi sarcoma and/or multicentric Castleman disease, comparable but less abnormal laboratory parameters, and a nonsignificant survival benefit. PEL cases with low apoptosis were associated with better prognosis. CONCLUSION: To the best of our knowledge, our case series of HIV-unrelated PEL is the largest thus far, expands the spectrum of cytological findings, and supports the need for a multidisciplinary approach in the diagnostic workup.