Intravascular NK/T-Cell Lymphoma: What We Know about This Diagnostically Challenging, Aggressive Disease.

Intravascular lymphoma is a form of lymphoid malignancy characterized by neoplastic cells growing almost exclusively within the lumina of small- to medium-sized blood vessels. Most cases are of B-cell origin with rare cases of natural killer or T-cell lineage. Extranodal sites are affected, mainly the skin and central nervous system, although any organ may be involved. Intravascular NK/T-cell lymphoma deserves special attention because of its clinicopathologic features and the need for adequate immunophenotyping combined with clonality test for a proper diagnosis. Moreover, intravascular NK/T-cell lymphoma is strongly linked to Epstein-Barr virus (EBV), which is considered to play a role in tumorigenesis and to be responsible for the aggressive behavior of the disease. In this paper, we review the current knowledge on this rare lymphoma and, in particular, the most recent advances about its molecular landscape. The main distinguishing features with other EBV-related entities, such as extranodal NK/T-cell lymphoma, EBV-positive primary nodal T/NK-cell lymphoma, and aggressive NK-cell leukemia, are discussed to help pathologists obtain the correct diagnosis and consequently develop an adequate and prompt therapy response.

Pediatric Thymoma: A Review and Update of the Literature.

Pediatric thymomas are extremely rare and slow-growing malignant tumors. The recent publication of the first Union for International Cancer Control (UICC)/American Joint Committee on Cancer (AJCC) Tumor-Node-Metastasis (TNM) stage classification and updated treatment guidelines for thymomas has prompted us to perform a review of the literature on pediatric thymomas. A search of English-language articles in the PubMed, Cochrane, Web of Science, and Embase databases was conducted. Additional articles were identified through reference lists of retrieved publications. Thirty-two articles involving 82 pediatric thymomas were included. Males comprised 60% of patients, and 13% manifested myasthenia gravis (MG). Histotype B1 (45%) and stage I (52% Masaoka-Koga and 71% UICC/AJCC TNM) were the most frequent. Of note is the possibility that the lack of cases with mixed histologies in the reviewed publications might be related to a sampling issue, as it is well known that the more sections are available for review, the more likely it is that the majority of these neoplasms will show mixed histologies. Both staging systems showed a gradual increase in the percentage of cases, with more advanced stages of disease moving from type A to B3 thymomas. Complete surgical resection (R0) was the main therapeutic approach in Masaoka-Koga stage I (89%) and UICC/AJCC TNM stage I (70%) thymomas. Advanced stages of disease and incomplete surgical resection were most often associated with recurrence and death. An association between stage and outcome, and completeness of resection and outcome, was found. Interestingly, though an association between histotype and staging was found, this does not take into account the possibility of mixed histologies which would reduce the clinical impact of histologic subtyping over staging.

Cutaneous Involvement in Diseases with Plasma Cell Differentiation: Diagnostic Approach.

Neoplasms with plasma cell differentiation may occasionally involve the skin. Cutaneous lesions may represent the first sign of an underlying systemic plasma cell malignancy, such as multiple myeloma, or the skin itself may be the primary site of occurrence of a hematological tumor with plasma cell differentiation. Starting from examples encountered in our daily practice, we discussed the diagnostic approach pathologists and clinicians should use when faced with cutaneous lesions with plasma cell differentiation. Cases of primary cutaneous marginal zone lymphoma, localized primary amyloidosis/amyloidoma, and cutaneous manifestations (secondary either to multiple myeloma or to plasmablastic lymphoma) are discussed, focusing on the importance of the adequate patient's work-up and precise clinicopathological correlation to get to the correct diagnosis and appropriate treatment. The pertinent literature has been reviewed, and the clinical presentation, pathological findings, main differential diagnoses, treatment, and outcome of neoplasms with plasma cell differentiation involving the skin are discussed.

Analysis of the Different Lymphatic Drainage Patterns during Sentinel Lymph Node Biopsy for Skin Melanoma.

In the last two decades, studies of lymphoscintigraphy imaging in lymphatic mapping reported an extreme heterogeneity of skin lymphatic drainage of some skin area, in contrast with the previous scientific literature. The aim of this study was to investigate the presence of any correlations between the topographical location of cutaneous melanoma and the topographical location of sentinel lymph nodes. Data from 165 patients undergoing sentinel lymph node biopsy between January 2013 and May 2021 were analyzed, demonstrating that melanomas in the Lumbar region presented a significant more heterogeneous drainage by site than those in the Scapular region (p < 0.01) and that melanomas in the Subscapular region were significantly more heterogeneous by laterality (unilateral vs. bilateral) than those in the Scapular region (p < 0.05). Results of this study supported the evidence of multiple lymphatic drainage as regards the sentinel node biopsy performed in skin melanoma located on the dorsal subscapular region and lumbar region. For this reason, the association of preoperative lymphoscintigraphy with another imaging evaluation is needed in these critical cutaneous areas. Recent technical developments enabling fluorescence lymphography together with indocyanine green have significantly improved the visualization of lymphatic drainage patterns at a microscopic level. In the preoperative phase, any doubt can be resolved by associating the SPET-CT scan to lymphoscintigraphy, while during the intraoperative phase, an additional evaluation with indocyanine green can be performed in doubtful cases. The aim of the duplex lymphatic mapping (pre and/or intraoperative) is an accurate search of sentinel nodes, in order to reduce the rate of false negatives.

Indolent T-Cell Lymphoproliferative Disorders of the Gastrointestinal Tract (iTLPD-GI): A Review.

iTLPD-GI is a low-grade clonal T-cell lymphoproliferative disease arising in GI organs. It is an uncommon disease, and only recently has it been enlisted as a distinct provisional entity in the current WHO Classification. Data from the literature disclose high heterogeneity in terms of pathological and molecular features; on the other hand, establishing an accurate diagnosis of iTLPD-GI is of pivotal importance, since treatment options are different from that of other, more frequent lymphomas that arise in the gastrointestinal tract. In this review, we aimed to better define this novel entity, and to identify useful diagnostic biomarkers; moreover, we provide a biomarker-based approach to the diagnosis and describe the most common issues in differentiating iTLPD-GI from other neoplastic and non-neoplastic disorders.

Primary effusion lymphoma occurring in the setting of transplanted patients: a systematic review of a rare, life-threatening post-transplantation occurrence.

BACKGROUND: Primary effusion lymphoma is a rare, aggressive large B-cell lymphoma strictly linked to infection by Human Herpes virus 8/Kaposi sarcoma-associated herpes virus. In its classic form, it is characterized by body cavities neoplastic effusions without detectable tumor masses. It often occurs in immunocompromised patients, such as HIV-positive individuals. Primary effusion lymphoma may affect HIV-negative elderly patients from Human Herpes virus 8 endemic regions. So far, rare cases have been reported in transplanted patients. The purpose of our systematic review is to improve our understanding of this type of aggressive lymphoma in the setting of transplantation, focusing on epidemiology, clinical presentation, pathological features, differential diagnosis, treatment and outcome. The role of assessing the viral serological status in donors and recipients is also discussed. METHODS: We performed a systematic review adhering to the PRISMA guidelines. The literature search was conducted on PubMed/MEDLINE, Web of Science, Scopus, EMBASE and Cochrane Library, using the search terms "primary effusion lymphoma" and "post-transplant". RESULTS: Our search identified 13 cases of post-transplant primary effusion lymphoma, predominantly in solid organ transplant recipients (6 kidney, 3 heart, 2 liver and 1 intestine), with only one case after allogenic bone marrow transplantation. Long-term immunosuppression is important in post-transplant primary effusion lymphoma commonly developing several years after transplantation. Kaposi Sarcoma occurred in association with lymphoma in 4 cases of solid organ recipients. The lymphoma showed the classical presentation with body cavity effusions in absence of tumor masses in 10 cases; 2 cases presented as solid masses, lacking effusions and one case as effusions associated with multiple organ involvement. Primary effusion lymphoma occurring in the setting of transplantation was more often Epstein Barr-virus negative. The prognosis was poor. In addition to chemotherapy, reduction of immunosuppressive treatment, was generally attempted. CONCLUSIONS: Primary effusion lymphoma is a rare, but often fatal post-transplant complication. Its rarity and the difficulty in achieving the diagnosis may lead to miss this complication. Clinicians should suspect primary effusion lymphoma in transplanted patients, presenting generally with unexplained body cavity effusions, although rare cases with solid masses are described.

Primary Pulmonary B-Cell Lymphoma: A Review and Update.

Primary pulmonary B-cell lymphomas (PP-BCLs) comprise a group of extranodal non-Hodgkin lymphomas of B-cell origin, which primarily affect the lung without evidence of extrapulmonary disease at the time of diagnosis and up to 3 months afterwards. Primary lymphoid proliferations of the lung are most often of B-cell lineage, and include three major entities with different clinical, morphological, and molecular features: primary pulmonary marginal zone lymphoma of mucosa-associated lymphoid tissue (PP-MZL, or MALT lymphoma), primary pulmonary diffuse large B cell lymphoma (PP-DLBCL), and lymphomatoid granulomatosis (LYG). Less common entities include primary effusion B-cell lymphoma (PEL) and intravascular large B cell lymphoma (IVLBCL). A proper workup requires a multidisciplinary approach, including radiologists, pneumologists, thoracic surgeons, pathologists, hemato-oncologists, and radiation oncologists, in order to achieve a correct diagnosis and risk assessment. Aim of this review is to analyze and outline the clinical and pathological features of the most frequent PP-BCLs, and to critically analyze the major issues in their diagnosis and management.

The broad landscape of follicular lymphoma: Part II.

Follicular lymphoma is a neoplasm derived from follicle center B cells, typically both centrocytes and centroblasts, in variable proportions according to the lymphoma grading. The pattern of growth may be entirely follicular, follicular and diffuse and rarely completely diffuse. It represents the second most common non-Hodgkin lymphoma, after diffuse large B-cell lymphoma and it is the most common low-grade mature B-cell lymphoma in Western countries. In the majority of cases, follicular lymphoma is a nodal tumor, occurring in adults and is frequently associated with the translocation t(14;18)(q32;q21)/IGH-BCL2. However, in recent years the spectrum of follicular lymphoma has expanded and small subsets of follicular lymphoma, which differ from common follicular lymphoma, have been identified and included in the current 2017 WHO classification. The aim of our review is to describe the broad spectrum of follicular lymphoma, pointing out that the identification of distinct clinicopathological variants of follicular lymphoma is relevant for the patient outcomes and treatment.

The broad landscape of follicular lymphoma: Part I.

Follicular lymphoma is a neoplasm derived from follicle center B cells, typically both centrocytes and centroblasts, in variable proportions according to the lymphoma grading. The pattern of growth may be entirely follicular, follicular and diffuse, and rarely completely diffuse. It represents the second most common non-Hodgkin lymphoma, after diffuse large B-cell lymphoma and is the most common low-grade mature B-cell lymphoma in western countries. In the majority of cases, follicular lymphoma is a nodal tumor, occurring in adults and frequently associated with the translocation t(14;18)(q32;q21)/IGH-BCL2. However, in recent years the spectrum of follicular lymphoma has expanded and small subsets of follicular lymphoma, which differ from common follicular lymphoma, have been identified and included in the current 2017 WHO classification. The aim of our review is to describe the broad spectrum of follicular lymphoma, pointing out that the identification of distinct clinicopathological variants of follicular lymphoma is relevant for patient outcomes and choice of treatment.