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Aims: Plasmablastic lymphoma (PBL) is a rare aggressive B‐cell lymphoma that frequently arises at extranodal sites in the setting of immunosuppression. The diagnosis of PBL is complex, owing to a frequent solid or cohesive growth pattern, and an often unusual immunophenotype. Several case reports have described cytokeratin (CK) expression in PBL, introducing a diagnostic pitfall. The aim of this study was to determine the frequency of CK expression in PBL in the largest series available to date. Methods and results: By using immunohistochemistry in a cohort of 72 PBLs, we identified CK8/18 positivity in 11 of 72 cases (15%) and AE1/3 positivity in six of 65 cases (9%), clearly contrasting with a control series of non‐PBL aggressive B‐cell lymphomas (one of 96 diffuse large B‐cell lymphomas), as well as with data in the literature describing only occasional CK expression in haematological neoplasms. Conclusions: Our data indicate CK expression in a substantial number (15%) of PBLs. In view of the particular morphological features of PBL and its frequent negativity for the common leukocyte antigen and B‐cell markers, this feature represents a pitfall in the routine diagnostic work‐up of PBL, and requires more extensive immunohistochemical and molecular characterisation of cases entering the differential diagnosis. [ABSTRACT FROM AUTHOR]

Both antigenic drive and genetic change play critical roles in the development of mucosa-associated lymphoid tissue (MALT) lymphoma, but neither alone is sufficient for malignant transformation, and lymphoma development critically depends on their cooperation. However, which of these different events concur and how they cooperate in MALT lymphomagenesis is totally unknown. To explore this, we investigated somatic mutations of 17 genes and immunoglobulin heavy chain variable region (IGHV) usage in 179 MALT lymphomas from various sites. We showed that: (1) there was a significant association between the biased usage of IGHV4-34 (binds to the carbohydrate I/i antigens) and inactivating mutation of TNFAIP3 [encoding a global negative regulator of the canonical nuclear factor-κB (NF-κB) pathway] in ocular adnexal MALT lymphoma; (2) IGHV1-69 was significantly overrepresented (54%) in MALT lymphoma of the salivary gland, but was not associated with mutation in any of the 17 genes investigated; and (3) MALT lymphoma lacked mutations that are frequently seen in other B-cell lymphomas characterized by constitutive NF-κB activities, including mutations in CD79B, CARD11, MYD88, TNFRSF11A, and TRAF3. Our findings show, for the first time, a significant association between biased usage of autoreactive IGHV and somatic mutation of NF-κB regulators in MALT lymphoma, arguing for their cooperation in sustaining chronic B-cell receptor signalling and driving oncogenesis in lymphoma development. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Aims Aggressive epidermotropic cutaneous CD8+ lymphoma is currently afforded provisional status in the WHO classification of lymphomas. An EORTC Workshop was convened to describe in detail the features of this putative neoplasm and evaluate its nosological status with respect to other cutaneous CD8+ lymphomas. Methods and results Sixty-one CD8+ cases were analysed at the workshop; clinical details, often with photographs, histological sections, immunohistochemical results, treatment and patient outcome were discussed and recorded. Eighteen cases had distinct features and conformed to the diagnosis of aggressive epidermotropic cutaneous CD8+ lymphoma. The patients typically present with widespread plaques and tumours, often ulcerated and haemorrhagic, and histologically have striking pagetoid epidermotrophism. A CD8+/ CD45 RA+/ CD45 RO−/ CD2−/ CD5−/ CD56− phenotype, with one or more cytotoxic markers, was found in seven of 18 patients, with a very similar phenotype in the remainder. The tumours seldom involve lymph nodes, but mucosal and central nervous system involvement are not uncommon. The prognosis is poor, with a median survival of 12 months. Examples of CD8+ mycosis fungoides, lymphomatoid papulosis and Woringer-Kolopp disease presented the typical features well documented in the CD4+ forms of those diseases. Conclusions Aggressive epidermotropic cutaneous CD8+ lymphoma is a distinct lymphoma that warrants inclusion as a distinct entity in future revisions of lymphoma classifications. [ABSTRACT FROM AUTHOR]

Abstract: A proportion of MYC translocation positive diffuse large B‐cell lymphomas (DLBCL) harbour a BCL2 and/or BCL6 translocation, known as double‐hit DLBCL, and are clinically aggressive. It is unknown whether there are other genetic abnormalities that cooperate with MYC translocation and form double‐hit DLBCL, and whether there is a difference in clinical outcome between the double‐hit DLBCL and those with an isolated MYC translocation. We investigated TP53 gene mutations along with BCL2 and BCL6 translocations in a total of 234 cases of DLBCL, including 81 with MYC translocation. TP53 mutations were investigated by PCR and sequencing, while BCL2 and BCL6 translocation was studied by interphase fluorescence in situ hybridization. The majority of MYC translocation positive DLBCLs (60/81 = 74%) had at least one additional genetic hit. In MYC translocation positive DLBCL treated by R‐CHOP (n = 67), TP53 mutation and BCL2, but not BCL6 translocation had an adverse effect on patient overall survival. In comparison with DLBCL with an isolated MYC translocation, cases with MYC/TP53 double‐hits had the worst overall survival, followed by those with MYC/BCL2 double‐hits. In MYC translocation negative DLBCL treated by R‐CHOP (n = 101), TP53 mutation, BCL2 and BCL6 translocation had no impact on patient survival. The prognosis of MYC translocation positive DLBCL critically depends on the second hit, with TP53 mutations and BCL2 translocation contributing to an adverse prognosis. It is pivotal to investigate both TP53 mutations and BCL2 translocations in MYC translocation positive DLBCL, and to distinguish double‐hit DLBCLs from those with an isolated MYC translocation. [ABSTRACT FROM AUTHOR]

Background: Atypical fibroxanthoma (AFX) is a distinctive clinicopathologic entity presenting on sun-damaged skin of the elderly. Its behavior is benign if strict diagnostic criteria are applied. Tumors showing invasion of deeper structures or perineural/lymphovascular invasion are best regarded as undifferentiated pleomorphic sarcoma of the skin. The diagnosis requires immunohistochemical studies to exclude melanoma, squamous cell carcinoma, angiosarcoma and leiomyosarcoma. Methods: Two AFX and one undifferentiated pleomorphic sarcoma showing aberrant expression of Melan-A were identified. Clinical data were obtained and histopathological features, immunohistochemical profile and electron microscopy were assessed. Results: All tumors arose on sun-damaged skin of elderly males. Two AFX showed pushing growth into superficial subcutis only. The undifferentiated pleomorphic sarcoma was characterized by infiltrative growth into galea as well as perineural invasion. Multifocal expression of Melan-A and MART-1 was largely limited to tumor giant cells in the absence of S100 or HMB-45 labeling. No melanosomes or premelanosomes were identified by electron microscopy. Conclusions: Aberrant expression of Melan-A and MART-1 in AFX and undifferentiated pleomorphic sarcoma of the skin represents an important diagnostic pitfall with potential for misdiagnosis as melanoma. Melan-A expression limited to tumor giant cells, in the absence of S-100 positivity, is a helpful diagnostic feature. Thum C, Hollowood K, Birch J, Goodlad JR, Brenn T. Aberrant Melan-A expression in atypical fibroxanthoma and undifferentiated pleomorphic sarcoma of the skin. [ABSTRACT FROM AUTHOR]

Christie L J, MacKenzie C, Palmer T J, Baker L & Goodlad J R (2011) Histopathology 59, 421-432 Type and maturational status of dendritic cells in cutaneous B cell lymphoproliferative disorders Aims: B cell cutaneous lymphoid hyperplasia (B-CLH) and cutaneous mucosa-associated lymphoid tissue (MALT) lymphoma represent opposite poles of the same disease spectrum. We explored the hypothesis that dendritic cells (DCs) are central in the generation and regulation of such lesions. Methods and results: Immunohistochemistry was used to identify Langerhan cells (LCs), dermal DCs (DDCs) and plasmacytoid DCs (PDCs), as well as mature and alternatively activated DCs, in B-CLH ( n = 14) and cutaneous MALT lymphoma ( n = 18). PDCs were most numerous in both types of lesion, but there were significantly more PDCs and DDCs and greater numbers of mature DCs in B-CLH. Nevertheless, DCs were still present in cutaneous MALT lymphoma and there were also proportionately more alternatively activated cells. Conclusion: Mature DDCs are prime activators of naive T cells and our results suggest that they are likely to be largely responsible for driving the initial proliferation in B-CLH. The results also suggest that PDCs play a central role, and we hypothesize that they dictate the magnitude, duration and direction of the response. In cutaneous MALT lymphoma PDCs are the dominant DC subtype, and may act by damping down the antitumour host immune response, as well as directly stimulating the growth and differentiation of the neoplastic lymphocytes. [ABSTRACT FROM AUTHOR]

AimsPrimary soft tissue lymphoma is uncommon and little is known regarding its aetiology and pathogenesis. In a review of 37 soft tissue lymphomas we uncovered three cases associated with rheumatoid arthritis which we report herein. Methods and resultsThe clinical records and pathology of the cases are described together with the results of in situ hybridization studies with oligonucleotide probes to Epstein–Barr virus (EBV) encoded RNA (EBER). All three patients were females with a long-standing history of rheumatoid arthritis ranging from 9 to 17 years. Each presented with a soft tissue mass in the vicinity of a joint affected by rheumatoid disease. All had received prior treatment with nonsteroidal anti-inflammatory drugs and one also received gold, penicillamine and intra-articular steroids to affected joints. None had received methotrexate. Histologically, the juxtaarticular soft tissue masses were all B-cell lymphomas. None were associated with EBV as determined by in situ hybridization. ConclusionsThese cases document an association between rheumatoid arthritis and soft tissue lymphoma of B-cell type, arising in the vicinity of an affected joint. Chronic local immune stimulation may have played a significant role in the genesis of these lymphomas, unlike the frequently reversible and EBV-positive lymphomas that occur in rheumatoid patients on immunosuppressive therapy. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 36-year-old Caucasian female with pyrexia and an elevated lactate dehydrogenase (LDH). Bone marrow trephine biopsy and cervical lymph node excision were carried out which reveals numerous fibrin ring granulomas present in the bone marrow with reactive T cell infiltration The article discusses fibrin ring granulomas associated with Epstein-Barr virus (EBV). It notes that bone marrow fibrin ring granulomas should be stimulating active work-up for EBV.

GLO:1XW/01may20:bjh16464-fig-0001.jpg PHOTO (COLOR): . gl A 32-year-old male with a history of stage 1A nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) treated four years previously with radiotherapy presented with weight loss. Contrast computed tomography (CT) of neck, thorax, abdomen and pelvis demonstrated widespread small-volume lymphadenopathy and 17-cm splenomegaly. Bone marrow trephine biopsy sections showed a hypercellular marrow with numerous large paratrabecular lymphoid aggregates. [Extracted from the article]