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Breast implant-associated anaplastic large cell lymphoma has been recognized as a distinct entity in the World Health Organization classification of hematolymphoid neoplasms. These neoplasms are causally related to textured implants that were used worldwide until recently. Consequently, there is an increased demand for processing periprosthetic capsules, adding new challenges for surgeons, clinicians, and pathologists. In the literature, the focus has been on breast implant-associated anaplastic large cell lymphoma; however, benign complications related to the placement of breast implants occur in up to 20% to 30% of patients. Imaging studies are helpful in assessing patients with breast implants for evidence of implant rupture, changes in tissues surrounding the implants, or regional lymphadenopathy related to breast implants, but pathologic examination is often required. In this review, we couple our experience with a review of the literature to describe a range of benign lesions associated with breast implants that can be associated with different clinical presentations or pathogenesis and that may require different diagnostic approaches. We illustrate the spectrum of the most common of these benign disorders, highlighting their clinical, imaging, gross, and microscopic features. Finally, we propose a systematic approach for the diagnosis and handling of breast implant specimens in general., Competing Interests: Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Isocitrate dehydrogenase 1 (IDH1) and IDH2 mutations occur in a variety of myeloid neoplasms. Immunohistochemistry (IHC)-based direct visualization of mutant clones of hematopoietic cells can be useful for rapid diagnostic screening and for monitoring treatment response. In this study, we first evaluated the sensitivity and specificity of the IDH1 p.R132H mutation-specific antibody by IHC. All IDH1 wild type cases (n=11) and IDH1 mutant cases with a non-p.R132H mutation (n=30) were negative by IHC, demonstrating 100% antibody specificity. All the initial diagnostic specimens with IDH1 p.R132H mutation including acute myeloid leukemia (n=30), myelodysplastic syndromes (MDS) (n=10), MDS/myeloproliferative neoplasms (MPN) (n=4), and MPN (n=5) were positive by IHC, demonstrating 100% antibody sensitivity. Both immature and mature myeloid cells showed immunoreactivity. Erythroid precursors, lymphoid cells, endothelial cells, and osteoblasts were consistently negative by IHC. We then evaluated the follow-up specimens with a known IDH1 mutation status including acute myeloid leukemia (n=23), MDS (n=2), MDS/MPN (n=2), and MPN (n=2). Thirty-three IDH1 p.R132H mutant cases were positive by IHC and 12 IDH1 mutation negative cases were negative by IHC. However, IHC reactivity in up to 25% of bone marrow cells was noted in 8 of 20 polymerase chain reaction-negative cases, all from patients with a known history of IDH1 p.R132H mutation indicating sampling error or a sensitivity issue with molecular tests. These data indicate that IHC is a highly specific and sensitive tool to detect IDH1 p.R132H mutation in bone marrow involved by myeloid neoplasms. In addition, IDH1 p.R132H IHC also allows localization and assessment of the maturation stage of the clones carrying the mutation.

Hepatosplenic T-cell lymphoma (HSTCL) is a rare, aggressive T-cell lymphoma that can be challenging to diagnose. In particular, distinguishing HSTCL from T-cell large granular lymphocytic (T-LGL) leukemia of γδ T-cell receptor (TCR) type is difficult without examination of a splenectomy specimen. In this study, we systematically assessed a series of HSTCL cases for findings reported in the literature as supporting or not supporting the diagnosis of HSTCL. We also compared HSTCL with a group of cases of T-LGL of γδ TCR type. Criteria assessed in this study included: B-symptoms, massive splenomegaly, lymphadenopathy, extranodal involvement, peripheral lymphocytosis, lymphoma cells that expand bone marrow sinuses, lymphocyte azurophilic granules, immunophenotype, evidence of infection by Epstein-Barr virus, human immunodeficiency virus, or human T-cell leukemia virus type 1, isochromosome 7q, trisomy 8, and TCR gene rearrangement status. On the basis of the data of this study, we conclude that massive splenomegaly, bone marrow sinusoidal expansion by lymphoma cells, and lymphocytes devoid of azurophilic granules were significantly more common in HSTCL patients than in γδ T-LGL patients (P<0.0001), and these features help support the diagnosis of HSTCL.

Hepatosplenic T-cell lymphoma (HSTCL) is a rare type of lymphoma. Patients have a poor prognosis, and there is no standard of care. We evaluated 28 HSTCL patients to determine factors that may be associated with outcome. There were 19 men and 9 women with a median age of 32.5 years. Most patients had massive splenomegaly, and bone marrow showed sinusoidal involvement by lymphoma. The HSTCL cells expressed γδ T-cell receptor (TCR) in 20 (74%), αβ TCR in 5 (19%), and neither in 2 (7%) patients (1 case not assessed). Conventional cytogenetics and/or fluorescence in situ hybridization analysis in 24 patients at diagnosis showed isochromosome 7q (i7q) in 10 (42%) and trisomy 8 in 8 (33%) patients. Median overall survival (OS) and event-free survival (EFS) were each 28.3 months. Serum bilirubin level ≥1.5 mg/dL, αβ TCR expression, and trisomy 8 each correlated significantly with shorter OS and EFS. Patients with HSTCL received a variety of chemotherapy regimens with no regimen better than any other. However, patients who underwent stem cell transplant showed longer survival (OS: hazard ratio 0.3, P=0.09; EFS: hazard ratio 0.2, P=0.034). In conclusion, although HSTCL patients have a poor prognosis overall, the data presented support the novel suggestions that HSTCL patients can be stratified into 2 prognostic groups, with an elevated serum bilirubin level, αβ TCR expression, and trisomy 8 identifying a poorer prognostic group. In addition, the outcomes of this patient cohort suggest that stem cell transplantation has value for the treatment of patients with HSTCL.

Iatrogenic immunodeficiency-associated lymphoproliferative disorders are rare. A small subset of these lesions resembles classical Hodgkin lymphoma (CHL), but there are few data in the literature about these lesions. We describe 10 patients with autoimmune diseases treated with immunomodulator therapeutic agents who developed CHL. The autoimmune diseases included rheumatoid arthritis (n=5), systemic lupus erythematosus (n=2), dermatomyositis (n=1), autoimmune hepatitis (n=1), and Crohn disease (n=1), and the immunomodulatory therapies were methotrexate, azathioprine, tumor necrosis factor-α inhibitors, and thalidomide alone or in various combinations. The study group included 9 women and 1 man with a median age of 50 years (range, 25 to 77 y). The histologic features supported CHL in all cases with Reed-Sternberg (RS) and Hodgkin (H) cells in an inflammatory cell background, although the neoplasm could only be subclassified in 3 patients: 2 nodular sclerosis and 1 mixed cellularity. Immunohistochemical analysis supported the diagnosis of CHL. In all cases the RS-H cells were CD30. Nine of 10 cases were CD15, whereas CD20 was expressed variably in 4/10 cases. CD45/LCA was negative in 8 cases assessed. In situ hybridization for Epstein-Barr virus-encoded RNA was positive in the RS-H cells in 8/10 cases. The microenvironment of these lesions depicted a predominance of T-regulatory cells and M2 histiocytes. Clinical follow-up data were available for 7 patients, with a median posttreatment period of 27 months (range, 12 mo to 7 y). In all 7 patients immunomodulatory drug therapy was discontinued, and chemotherapy for CHL was administered; 2 patients also received local radiation. All 7 patients achieved complete remission and are alive. We conclude that iatrogenic immunodeficiency-associated CHL is highly associated with Epstein-Barr virus infection, and patients usually have a good outcome after discontinuation of immunomodulatory agents and chemotherapy for CHL.

Extranodal NK/T-cell lymphoma, nasal type (ENKTL) is uncommon in the United States. We report 73 patients with ENKTL, including 49 men and 24 women (median age, 46 y). Sixty-three patients had nasal/upper aerodigestive tract disease; 10 had extranasal disease involving skin, small intestine, epiglottis, testis, adrenal glands, kidney, and breast. Complete staging data were available for 68 patients: 44 stage I/II and 24 stage IV. Fifteen of 69 (22%) had lymphadenopathy and 10/63 had bone marrow involvement. Histologically, 67/73 (92%) showed necrosis, and 48/70 (69%) had an angiocentric/angiodestructive growth pattern. The neoplastic cells showed a wide spectrum: medium sized (n=34), mixed small and large (n=21), large (n=13), and small (n=5). In situ hybridization for Epstein-Barr virus-encoded small RNA was positive in every case. Immunohistochemical studies showed expression of cytotoxic markers (100%), T-bet (96%), CD2 (96%), CD3 (93%), CD56 (90%), and ETS-1 (64%). Ki-67 was ≥60% in 46% cases. Therapy was known for 64 patients; 14 received only chemotherapy, 8 radiation alone, and 42 received combined radiation and chemotherapy. Median survival was 4.2 years, and 5-year overall survival was 46% (median follow-up, 3.8 y). Extranasal disease, high International Prognostic Index score, and high proliferation rate correlated with poorer prognosis. We conclude that ENKTL cases in the United States are similar to those reported in Asia and other countries. Absence of the angiocentric/angiodestructive pattern and presence of lymphadenopathy, features underemphasized in the literature, occurred in appreciable subsets of patients. The International Prognostic Index score, anatomic site of disease, and proliferation rate had prognostic value in this patient cohort.

The inv(16)(p13q22) or, less commonly the t(16;16)(p13;q22), is characteristic of acute myeloid leukemia (AML) with abnormal bone marrow eosinophils, also known as AML-M4Eo. This abnormality creates a fusion gene, 5' core binding factor beta (CBF-beta) gene and the 3' MYH11 gene, the latter encoding smooth muscle myosin heavy chain gene (SMMHC). Detection of this abnormality is important for diagnosis and is most commonly done by cytogenetics or molecular methods. In this study, we determined the utility of immunohistochemical and immunofluorescence methods using a rabbit polyclonal antibody (AH107) against the C-terminus of the CBFbeta-SMMHC chimeric protein for diagnosis of AML-M4Eo. Thirty-nine AML-M4Eo cases and 55 cases of other types of AML were evaluated. Immunohistochemical analysis of routinely processed paraffin-embedded bone marrow sections showed that CBFbeta-SMMHC staining is predominantly nuclear in all cases of AML-M4Eo and is not nuclear in other AML types. Four cases of AML-M4Eo double-stained for CBFbeta-SMMHC and CD34 showed the fusion protein in CD34-positive blasts. Indirect immunofluorescence analysis of fresh bone marrow aspirate smears showed that AML-M4Eo blasts have a distinct nuclear microgranular or fine-speckled pattern of staining, with or without faint cytoplasmic staining. By contrast, other types of AML and normal bone marrow specimens were either negative or had a nonspecific pattern of staining. In summary, immunostaining for CBFbeta-SMMHC using either immunohistochemical or immunofluorescense analysis as described here reveals a distinctive pattern of staining for AML-M4Eo. This approach is a specific, reliable, and convenient alternative to cytogenetic and molecular methods for the diagnosis of AML-M4Eo and may be particularly helpful in cases with indeterminate histologic features or in cases in which cytogenetic and molecular studies are either uninformative or not available.

The growth of angioimmunoblastic T-cell lymphoma (AIL) in lymph node often produces complex patterns of neoplastic T cells and nonneoplastic B cells that complicate diagnosis. To understand better how these different patterns of B-cell expansion arise, we compared the microanatomic localization of B cells and T cells within the follicular, paracortical, and sinusoidal compartments in 30 patients with AIL (including 10 with multiple sequential samples) with that seen in 33 cases of other types of T-cell lymphoma. With early or partial nodal involvement in AIL, germinal center B-cell expansions were relatively undisturbed and often associated with a variably distended D2-40+ CD31+ perifollicular sinus that surrounded most of the follicular compartment. Identifiable tumor T cells resided mostly in the paracortex. In later stages of AIL with more complete nodal effacement, bcl-6+ follicular B-cell proliferations shifted to distorted FDC networks arrayed along patent trabecular sinuses and were more intermixed with tumor T cells. In both AIL and other T-cell lymphomas, the density and locations of follicular B cells as well as bcl-6-negative monocytoid B cells were largely related to the patency of adjacent sinuses, except in Epstein-Barr virus (EBV)+ and histiocyte-rich B-cell proliferations, which arose in paracortical locations. The prominence of the perifollicular sinus in early stages of AIL resembled that seen in reactive lymphadenitis during conditions of lymphatic engorgement and implicates cytokines within lymph fluid in maintaining both the normal and altered germinal center reactions. Patterns of sinus drainage largely explain the useful changes in B-cell distribution that occur in nodal T-cell lymphomas and represent an important tool in classification and diagnosis of these tumors.