Bone Marrow and Peripheral Blood Findings in Patients Infected by SARS-CoV-2.

Objectives: Coronavirus disease 19 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is associated with diverse clinical, including hematologic, abnormalities. We describe peripheral blood and bone marrow findings in deceased and living patients with COVID-19.

Methods: We examined bone marrows from 20 autopsies and 2 living patients with COVID-19 using H&E-stained slides and immunohistochemical stains.

IgG4-related Lymphadenopathy: A Comparative Study of 41 Cases Reveals Distinctive Histopathologic Features.

Lymphadenopathy is common in patients with immunoglobulin G4-related disease (IgG4-RD). However, the described histopathologic features of IgG4-related lymphadenopathy have been shown to be largely nonspecific. In an attempt to identify features specific for nodal IgG4-RD we examined the histopathologic features of lymph nodes from 41 patients with established IgG4-RD, with comparison to 60 lymph nodes from patients without known or subsequent development of IgG4-RD.

NK-Cell Enteropathy and Similar Indolent Lymphoproliferative Disorders: A Case Series With Literature Review.

Objectives: We report four new cases of natural killer-cell enteropathy (NKCE) and similar lymphoproliferative disorders (LPDs), as well as review the literature concerning indolent natural killer (NK)-cell LPDs of the gastrointestinal tract.

Methods: Pathologic and clinical data were obtained from institutional/referral records.

Results: Patient 1 (45-year-old man) had anemia; a small intestinal lesion was endoscopically biopsied.

IgG4-related disease: review of the histopathologic features, differential diagnosis, and therapeutic approach.

Immunoglobulin G4-related disease (IgG4-RD) is an uncommon disorder that demonstrates characteristic clinicopathologic features including sclerosing lesions with storiform fibrosis, increased IgG4+ plasma cells with an increased IgG4+/IgG+ plasma cell ratio, obliterative phlebitis, and often an increased serum IgG4 level. This review summarizes the characteristic histopathologic and clinical features of IgG4-RD with detailed discussion of the histopathologic characteristics of the most commonly involved anatomic sites. We also present recent advances in our understanding of the pathophysiologic mechanisms of IgG4-RD and discuss updates on the treatment, prognosis, and outcomes of this rare disease, including discussion of the possible association between IgG4-RD and malignancy.

Heavy Chain Disease of the Small Bowel.

Purpose Of Review: The purpose of this review is to discuss current knowledge and recent findings regarding pathogenesis, outcome, and treatment for heavy chain disease (HCD) involving the small bowel, focusing on alpha HCD or immunoproliferative small intestinal disease (IPSID), the HCD subtype typically affecting the small bowel.

Recent Findings: A link between Campylobacter jejuni infection and IPSID has been established, but there is controversy as to the role played by this organism in disease pathogenesis. While cytogenetic abnormalities involving various immunoglobulin loci and PAX5 have been reported, these have been described in rare, single cases, limiting their ability to shed further light on disease pathogenesis.

Lymphomas in IgG4-related disease: clinicopathologic features in a Western population.

Lymphomas that occur in the setting of IgG4-related disease (IgG4-RD) are uncommon. Most reported cases derive from Asia and are MALT lymphomas occurring in orbital IgG4-RD. The spectrum of lymphomas among IgG4-RD patients in the Western world remains poorly defined.

There Are No Magic Bullets in Hematopathology: Even Immunostains for CD20 and CD3 Can Get You Into Trouble.

Immunohistochemistry is a powerful tool for the diagnosis and subclassification of hematolymphoid neoplasms. However, the expression of certain markers is not always as expected, and unusual patterns of staining can lead to misdiagnosis. CD20 and CD3 are our most commonly used markers for identification of B cells and T cells, respectively, and they almost always yield reliable, specific staining.

Fibrin-associated EBV-positive Large B-Cell Lymphoma: An Indolent Neoplasm With Features Distinct From Diffuse Large B-Cell Lymphoma Associated With Chronic Inflammation.

Incidental cases of localized fibrin-associated Epstein-Barr virus (EBV)+ large B-cell proliferations have been described at unusual anatomic sites and have been included in the category of diffuse large B-cell lymphoma associated with chronic inflammation (DLBCL-CI) in the WHO Classification. We describe 12 cases and review the literature to define their clinicopathologic spectrum and compare features with typical cases of DLBCL-CI. Median age was 55.

EBV-negative monomorphic B-cell post-transplant lymphoproliferative disorders are pathologically distinct from EBV-positive cases and frequently contain TP53 mutations.

Monomorphic post-transplant lymphoproliferative disorder commonly resembles diffuse large B-cell lymphoma or Burkitt lymphoma, and most are Epstein-Barr virus (EBV) positive. We retrospectively identified 32 cases of monomorphic post-transplant lymphoproliferative disorder from two institutions and evaluated EBV in situ hybridization; TP53 mutation status; p53, CD30, myc, and BCL2 expression by immunohistochemistry; proliferation index by Ki67; and germinal center vs non-germinal center immunophenotype by Hans criteria. Post-transplant lymphoproliferative disorder arose after hematopoietic stem cell transplant in five and solid organ transplant in 27 patients, a median of 4 and 96 months after transplant, respectively (overall median latency 71 months, range 2-295).

Small-cell predominant extranodal NK/T cell lymphoma, nasal type: clinicopathological analysis of a series of cases diagnosed in a Western population.

Aims: Extranodal NK/T cell lymphoma, nasal type (ENKTCL) is usually composed of medium- to large-sized lymphoid cells showing prominent angiotrophism and tumour cell necrosis. We report 13 cases composed predominantly of small lymphocytes diagnosed in the United States and Western Europe.

Methods And Results: Patients included seven females and six males aged 17-75 years.

Differential expression of E-cadherin and catenins in ovarian sex cord stromal tumours.

Aims: Sex cord stromal tumours (SCSTs) of the ovary encompass several histological tumour subtypes that are defined by characteristic histological features. Some can show morphological overlap with other subtypes of SCSTs, as well as with non-SCSTs. The E-cadherin/catenin complex constitutes the adherens junction, which is well developed in epithelial tissue, but the constituent molecules are also expressed in several non-epithelial tumours.

IgG4-related Orbital Disease and Its Mimics in a Western Population.

Although chronic inflammatory disorders of the ocular adnexa are relatively common, their pathogenesis is in many cases poorly understood. Recent investigation suggests that many cases of sclerosing orbital inflammation are a manifestation of IgG4-related disease; however, most patients reported have been Asian, and it is not clear whether the results of studies from the Far East can be reliably extrapolated to draw conclusions about Western patients. We evaluated 38 cases previously diagnosed as orbital inflammatory pseudotumor or chronic dacryoadenitis to determine whether our cases fulfill the criteria for IgG4-RD (IgG4-related dacryoadenitis when involving the lacrimal gland, and IgG4-related sclerosing orbital inflammation when involving orbital soft tissue).

Microcystic Stromal Tumor: A Distinctive Ovarian Sex Cord-Stromal Neoplasm Characterized by FOXL2, SF-1, WT-1, Cyclin D1, and β-catenin Nuclear Expression and CTNNB1 Mutations.

Since our first description of the microcystic stromal tumor (MST) of the ovary, a rare and distinctive neoplasm with a definitional, usually striking microcystic pattern and a CD10+/vimentin+/inhibin-/calretinin- immunophenotype, 3 examples with β-catenin nuclear localization, and CTNNB1 mutation have been reported. We undertook a detailed immunohistochemical study and molecular analysis of CTNNB1 and FOXL2 of 15 cases of MST to further characterize this neoplasm and establish its histogenesis. Diffuse nuclear staining for FOXL2, WT-1, cyclin D1, and β-catenin was present in all tumors tested, and 12/15 were positive for steroidogenic factor-1 (SF-1).

Diverse clinicopathologic features in human herpesvirus 8-associated lymphomas lead to diagnostic problems.

Objectives: Human herpesvirus 8 (HHV8)-associated lymphomas are uncommon, mainly affect men infected with the human immunodeficiency virus (HIV), and usually have a poor prognosis. We sought to characterize the HHV8+ lymphomas seen at our institution since the mid-1990s.

Methods: We identified 15 patients with HHV8-associated lymphomas and evaluated their clinical and pathologic features.

Primary endometrioid stromal sarcoma of the ovary: a clinicopathologic study of 27 cases with morphologic and behavioral features similar to those of uterine low-grade endometrial stromal sarcoma.

Twenty-seven endometrioid stromal sarcomas of the ovary from patients 38 to 76 (mean 56) years of age are reported. The tumors were unilateral in 20 cases and bilateral in 7. They were solid (9), solid and cystic (9), or predominantly cystic (6) when this information was known and ranged from 1 to 20 (mean 9.

IgG4-related disease in the head and neck.

Lymphoid infiltrates are relatively common in the ocular adnexa and the salivary glands. They are of a variety of types and include both reactive processes and lymphomas. Within the ocular adnexa in years past, lymphoid proliferations were classified as inflammatory pseudotumor, reactive lymphoid hyperplasia, atypical lymphoid hyperplasia, and lymphoma.

Metastases to and from the Breast.

Breast cancer is a common source of systemic metastatic disease. Distinguishing metastatic breast cancer from other types of malignancies can be diagnostically challenging but is important for correct treatment and prognosis. Nonmammary tumors can also metastasize to the breast, although this is a rare phenomenon.

The Warrens and other pioneering clinician pathologists of the Massachusetts General Hospital during its early years: an appreciation on the 200th anniversary of the hospital founding.

To celebrate the bicentennial of the 1811 charter to establish the Massachusetts General Hospital, we tell the stories of the physicians and surgeons of the hospital who practiced pathology until the discipline was more firmly established with the recruitment of James Homer Wright who became the first full-time pathologist at the hospital in 1896. One of the two co-founders of the hospital, John Collins Warren (famed primarily for being the surgeon at the first public demonstration of ether anesthesia) had a major interest in pathology; he published a book focused on gross pathology (1837) and began the important specimen collection subsequently known as the Warren Anatomical Museum at Harvard Medical School (HMS). An early physician, John Barnard Swett Jackson, became the first professor of pathology in the United States (1847) and was a noted collector whose specimens were added to the Warren Museum.

Recent Advances in Follicular Lymphoma: Pediatric, Extranodal, and Follicular Lymphoma in Situ.

Follicular lymphoma is a relatively common B-cell lymphoma composed of follicle center B lymphocytes. Follicular lymphomas occurring in the pediatric population and in some extranodal sites exhibit particular clinicopathologic features and clinical behavior that are often distinct from adult nodal follicular lymphoma. A type of "in-situ" follicular lymphoma presents as intrafollicular neoplastic cells in a background of architecturally normal lymphoid tissue and may be difficult to recognize in routine sections.

Use of Myoepithelial Cell Markers in the Differential Diagnosis of Benign, In situ, and Invasive Lesions of the Breast.

Immunohistochemical markers for myoepithelial cells are commonly used to distinguish invasive from noninvasive lesions in the breast. The approach takes advantage of the fact that conventional invasive carcinomas lack surrounding myoepithelial cells, whereas nearly all benign lesions and in situ carcinomas retain their myoepithelial cell layer. Although conceptually straightforward, the interpretation of myoepithelial cell markers can be complicated by misleading patterns of reactivity (such as stromal or tumor cell staining) or lack of reactivity (due to reduced numbers of myoepithelial cells or variable antigenicity).

HHV-8+, EBV+ multicentric plasmablastic microlymphoma in an HIV+ Man: the spectrum of HHV-8+ lymphoproliferative disorders expands.

Human herpesvirus-8 (HHV-8) is associated with several distinct lymphoproliferative disorders: primary effusion lymphoma, multicentric Castleman disease (MCD), MCD-associated plasmablastic lymphoma and HHV-8+, Epstein-Barr virus (EBV)+ germinotropic lymphoproliferative disorder. We report the case of a human immunodeficiency virus (HIV)+ male with fever, generalized lymphadenopathy, and splenomegaly. Two peripheral lymph nodes were excised and showed features of MCD and a prominent proliferation of HHV-8+, EBV+, CD20, CD138, MUM1+, lambda dim+, Ig heavy chain plasmablasts and immunoblasts replacing some follicles.

Classical Hodgkin's lymphoma presenting as a testicular mass: report of a case.

Hodgkin's lymphoma almost always presents with lymphadenopathy. Presentation with extranodal disease is quite unusual, although Hodgkin's lymphoma is known to occasionally involve extranodal sites. However, no well-documented cases of testicular Hodgkin's lymphoma have been described.

From Krukenberg to today: the ever present problems posed by metastatic tumors in the ovary. Part II.

This is the second of a two-part consideration of metastatic tumors to the ovary. Here, the matter is considered in 16 categories, largely site-specific. The first tumor discussed is gastric carcinoma of intestinal-type whose ovarian manifestations have been the subject of a recent paper which emphasized its differences from the Krukenberg tumor.

Lymphoma of the ocular adnexa: A study of 353 cases.

We studied the cases of 353 patients with lymphoma involving the ocular adnexa diagnosed at the Massachusetts General Hospital between 1974 and 2005. The patients included 153 males and 200 females, aged 7 to 95 years, with a mean age of 64 years. In 277 cases, there was no known history of lymphoma.