The Utility of Thromboelastography in Monitoring Von Willebrand Disease: A Case Report.

Von Willebrand disease (VWD) is the most common inherited bleeding disorder. It is primarily attributed to malfunctioning or deficient Von Willebrand factor (VWF). Thromboelastography (TEG) has emerged as a valuable tool for assessing coagulation dynamics and guiding transfusion therapy in bleeding patients. Given this, we present a case study of a 23-year-old pregnant female with a past medical history of type 2B VWD, wherein TEG was employed to optimize disease screening and therapy monitoring while minimizing costs and preventing complications associated with low platelet counts. This case underscores the potential utility of TEG in enhancing the care of VWD patients, particularly in unique critical settings such as pregnancy.

High-Grade B-Cell Lymphoma With Malignant Effusions as the Initial Presentation.

OBJECTIVES: Malignant effusion is usually caused by metastatic carcinoma. Malignant lymphoma is often not included as a top differential diagnosis of malignant effusion. Here, we describe 3 cases of young female patients with no significant past medical history who presented with fluid overload and were diagnosed with high-grade B-cell lymphoma (HGBL). METHODS: We conducted histopathologic examination and immunophenotypic and cytogenetic analyses on three cases using immunohistochemistry, flow cytometry, fluorescence in situ hybridization (FISH), and karyotyping. We also included patients' clinical and radiological findings in our case reports. RESULTS: Histologic examination of the effusion samples showed numerous intermediate to large lymphoma cells with irregular nuclear contours and fine chromatin. The lymphoma cells were positive for CD10, CD20, BCL2, BCL6, and PAX5 and negative for CD34, cyclin D1, HHV-8, and TdT. In situ hybridization for Epstein-Barr virus (EBV)-encoded small RNAs was negative. The proliferation index by Ki-67 stain was more than 80%. Flow cytometry showed CD10-positive B cells with monotypic immunoglobulin light chain expression. Fluorescence in situ hybridization analysis demonstrated MYC, BCL2, or BCL6 rearrangements. These 3 patients were diagnosed as having HGBL with double-/triple-hit rearrangements. Despite receiving aggressive chemotherapy, all 3 patients had a dismal clinical course, with 2 patients dying less than 2 years after initial diagnosis. CONCLUSIONS: High-grade B-cell lymphoma should be considered in the differential diagnoses of malignant effusions. Flow cytometric and FISH analyses of the body fluid specimens are essential to reach an accurate and timely diagnosis.

T-Cell Prolymphocytic Leukemia With t(X;14)(q28;q11.2): A Clinicopathologic Study of 15 Cases.

OBJECTIVES: T-cell prolymphocytic leukemia (T-PLL) is a rare mature T-cell leukemia usually characterized by inv(14)(q11.2q32)/t(14;14)(q11.2;q32). In this study, we aimed to investigate the clinicopathologic features and molecular profile of T-PLL associated with t(X;14)(q28;q11.2). METHODS: The study group included 10 women and 5 men with a median age of 64 years. All 15 patients had a diagnosis of T-PLL with t(X;14)(q28;q11.2). RESULTS: All 15 patients had lymphocytosis at initial diagnosis. Morphologically, the leukemic cells had features of prolymphocytes in 11 patients, small cell variant in 3, and cerebriform variant in 1. All 15 patients had hypercellular bone marrow with an interstitial infiltrate in 12 (80%) cases. By flow cytometry, the leukemic cells were surface CD3+/CD5+/CD7+/CD26+/CD52+/TCR α/ß+ in 15 (100%) cases, CD2+ in 14 (93%) cases, CD4+/CD8+ in 8 (53%) cases, CD4+/CD8- in 6 (40%) cases, and CD4-/CD8 + in 1 (7%) case. At the cytogenetic level, complex karyotypes with t(X;14)(q28;q11.2) were seen in all 15 patients assessed. Mutational analysis showed mutations of JAK3 in 5 of 6 and STAT5B p.N642H in 2 of 6 patients. Patients received variable treatments, including 12 with alemtuzumab. After a median follow-up of 17.2 months, 8 of 15 (53%) patients died. CONCLUSIONS: T-PLL with t(X;14)(q28;q11.2) frequently shows a complex karyotype and mutations involving JAK/STAT pathway, and it is an aggressive disease with a poor outcome.

Cystic Encapsulated Papillary Carcinoma in the Male Breast: An Unusual Feature With a Diagnostic Challenge.

Papillary carcinoma in the male breast is uncommon. Here, we report a case of a large encapsulated papillary carcinoma (EPC) in a 62-year-old male. The patient presented with a left breast mass of 1-year duration and bloody nipple discharge for several days. Mammography and breast ultrasonography showed a large left breast mass. The initial biopsy demonstrated fat necrosis with acute and chronic inflammation only. Due to clinical suspicion, a repeat biopsy was performed and revealed scant fragments of papillary carcinoma in a background of inflammation. The patient underwent left total mastectomy. Grossly, the breast contained a 9.0 cm entirely cystic lesion lined by a hemorrhagic thick fibrotic wall. No solid area was identified in the cyst. The entire cyst wall was examined under microscopy; only a few sections with papillary carcinoma were identified. The lesion was confined to the cyst wall; so, a diagnosis of EPC was made. Compared to the previously reported EPC cases of male breast, the lesion of this case was unusually cystic, which making the diagnosis challenging. Therefore, awareness of this unusual feature, repeat biopsy when the pathology result is discordant, and extensive sampling of the lesion are essential for making the correct diagnosis and guiding patient management.

A Case Report of Fetal Thrombotic Vasculopathy in a COVID Placenta.

COVID-19 has affected patients of all ages and demographics, not excluding pregnant women. The effects of COVID-19 on pregnant women are still largely unknown. Several adverse perinatal outcomes have been reported in COVID-19-positive pregnant women, including pre-eclampsia, miscarriage, pre-term labor, and stillbirth. Histopathological examination of COVID-19 placentas can contribute significant data regarding maternal and fetal health and can elucidate more findings in this novel disease. A 23-year-old female with morbid obesity and scant antenatal care presented to the emergency department complaining of shortness of breath and fever; she was found to be positive for COVID-19. Grossly, her placenta showed no abnormalities. Histological examination of her placenta showed chronic lymphoplasmacytic deciduitis, villous fibrosis, loss of capillarization, extravasation of erythrocytes, chorangiosis, and thrombosis of upstream stem vessels, including large fetal vessels on the chorionic plate. These changes were deemed to be consistent with fetal thrombotic vasculopathy (FTV). In conclusion, this case of FTV in the placenta of a patient with COVID-19 is a significant finding, as it can be critical to clinicians in the management of prenatal care for expecting mothers during this pandemic.This case was presented at the annual meeting of the Association of Clinical Scientists (ACS) on May 13, 2021.

Pathology Residency Curriculum: Time for a Change?

The current Anatomical and Clinical Pathology residency curriculum, as outlined by the American Board of Pathology (ABP), emphasizes resident exposure to a wide variety of subjects without in-depth training. This has led to a large number of residents pursuing fellowship training. With the demand for further sub-specialization, there is a necessity for the establishment of an updated curriculum that not only encompasses the basic knowledge of pathology but is also focused on training residents in their desired subspecialty.We herein propose a new comprehensive AP/CP residency syllabus. The new curriculum will be divided into two major categories: preliminary and subspecialty training. The curriculum will require residents to undergo basic pathology training within the first two preliminary years, followed by two subspecialty years. In their subspecialty years, each resident will be required to either pick two subjects as majors, each having a duration of one year, or one subject as a major and two subjects as minors, in which case the major will have a one-year duration and the minors will each be six months in length. The proposed curriculum meets the current guidelines of the ABP, reduces the burden of residents to complete multiple fellowships, and allows residents earlier entrance into the workforce.

Obesity Is a Risk Factor Associated with H. pylori-negative MALT Lymphoma of Stomach.

OBJECTIVE: More than 90% of gastric mucosa-associated lymphoid tissue (MALT) lymphomas are attributed to Helicobacter pylori infections. However, the pathogenesis of H. pylori-negative MALT lymphomas is controversial, and additional etiologies need to be investigated. MATERIALS: A retrospective study of gastric MALT lymphoma cases over a 15-year period revealed 56 cases. The H. pylori status, clinical information, and body mass index (BMI) data were collected. The results of the urea breath test, serology, stool antigen, and previous biopsy results were documented. RESULTS: The 56 cases had an average height of 166.57 cm (range, 147.3-190.5), weight of 83.98 kg (range 55-153.1), and body mass index (BMI) of 30.34 kg/m2 (range, 17.96-49.77). Twenty-one cases were H. pylori-positive (37.5%), with a mean BMI of 27.36 kg/m2 (range, 17.96-47.25), and BMI>30 kg/m2 in 5 (23.8%) patients. Thirty-five cases were H. pylori-negative, with a mean BMI of 31.90 kg/m2 (range, 18.17-49.77), and 20 (57.1%) having BMI>30 kg/m2. A Fisher's exact test and two-tailed test showed a statistically significant difference between the two groups. CONCLUSION: Obesity leads to a baseline state of chronic inflammation and increased production of pro-inflammatory cytokines that can stimulate the lymphocytes, leading to lymphomatous proliferation. Our study suggests a potential correlation between obesity and the risk of development of primary gastric MALT lymphoma.

Primary Effusion Lymphoma: A Clinicopathological Study of 70 Cases.

Primary effusion lymphoma (PEL) is a rare type of large B-cell lymphoma associated with human herpesvirus 8 (HHV8) infection. Patients with PEL usually present with an effusion, but occasionally with an extracavitary mass. In this study, we reported a cohort of 70 patients with PEL: 67 men and 3 women with a median age of 46 years (range 26-91). Of these, 56 (80%) patients had human immunodeficiency virus (HIV) infection, eight were HIV-negative, and six had unknown HIV status. Nineteen (27%) patients had Kaposi sarcoma. Thirty-five (50%) patients presented with effusion only, 27 (39%) had an extracavitary mass or masses only, and eight (11%) had both effusion and extracavitary disease. The lymphoma cells showed plasmablastic, immunoblastic, or anaplastic morphology. All 70 (100%) cases were positive for HHV8. Compared with effusion-only PEL, patients with extracavitary-only PEL were younger (median age, 42 vs. 52 years, p = 0.001), more likely to be HIV-positive (88.9% vs. 68.6%, p = 0.06) and EBV-positive (76.9% vs. 51.9%, p = 0.06), and less often positive for CD45 (69.2% vs. 96.2%, p = 0.01), EMA (26.7% vs. 100%, p = 0.0005), and CD30 (60% vs. 81.5%, p = 0.09). Of 52 (50%) patients with clinical follow-up, 26 died after a median follow-up time of 40.0 months (range 0-96), and the median overall survival was 42.5 months. The median OS for patients with effusion-only and with extracavitary-only PEL were 30.0 and 37.9 months, respectively (p = 0.34), and patients with extracavitary-only PEL had a lower mortality rate at the time of last follow-up (35% vs. 61.5%, p = 0.07). The median OS for HIV-positive and HIV-negative patients were 42.5 and 6.8 months, respectively (p = 0.57), and they had a similar mortality rate of 50% at last follow-up. In conclusion, patients presenting with effusion-only versus extracavitary-only disease are associated with different clinicopathologic features. PEL is an aggressive lymphoma with a poor prognosis, regardless of extracavitary presentation or HIV status.

Cryptic Acute Promyelocytic Leukemia (APL) Presenting as Seizures in an Adolescent.

There are approximately 800 new cases of acute promyelocytic leukemia (APL) in the United States every year. APL is rarely observed in pediatric populations, and accounts for less than 5-10% of all pediatric cases of acute myeloid leukemia (AML). APL typically presents with symptoms related to the pancytopenia such as fatigue due to anemia, bleeding and bruising secondary to thrombocytopenia, and infections attributed to a lack of functioning leukocytes. The presentation of APL in the central nervous system (CNS) is a rare phenomenon. In addition, APL has a dismal prognosis when found in the CNS. In this case study, we describe a unique presentation of pediatric APL with cryptic insertion of the promyelocytic leukemia (PML)-retinoic acid receptor-alpha (RARA) fusion protein with a surprisingly excellent recovery.

An Incidental Finding of Gastric Mucosa-Associated Lymphoma (MALToma) in a Sleeve Gastrectomy with Literature Review.

Mucosal-associated lymphoid tissue (MALT) lymphoma can typically be identified as a mass lesion or nodularity endoscopically and macroscopically. We report an incidental finding of a Helicobacter pylori gastric mucosal-associated lymphoid tissue (MALT) lymphoma in a sleeve gastrectomy specimen with no gross examination findings.

Educational Case: Systemic Mastocytosis with an Associated Hematological Neoplasm.

The following fictional case is intended as a learning tool within the Pathology Competencies for Medical Education (PCME), a set of national standards for teaching pathology. These are divided into three basic competencies: Disease Mechanisms and Processes, Organ System Pathology, and Diagnostic Medicine and Therapeutic Pathology. For additional information, and a full list of learning objectives for all three competencies, see http://journals.sagepub.com/doi/10.1177/2374289517715040.1.

Educational Case: Mantle Cell Lymphoma.

The following fictional case is intended as a learning tool within the Pathology Competencies for Medical Education (PCME), a set of national standards for teaching pathology. These are divided into three basic competencies: Disease Mechanisms and Processes, Organ System Pathology, and Diagnostic Medicine and Therapeutic Pathology. For additional information, and a full list of learning objectives for all three competencies, see http://journals.sagepub.com/doi/10.1177/2374289517715040.1.

HIV-associated plasmablastic lymphoma in the era of HAART: a single-center experience of 21 patients.

OBJECTIVES: Patients with HIV infection have an increased risk of developing plasmablastic lymphoma (PBL). In this study, we reviewed the clinicopathologic features of PBL in HIV+ patients in the era of HAART from a single health center. DESIGN: Retrospective study. METHODS: The morphologic, immunophenotypic, and clinical features were reviewed in these HIV+ patients with PBL and univariate analysis was employed to determine the survival prognosis. RESULTS: During the interval of 1 January 2008 to 30 December 2018, we identified 95 HIV+ patients with aggressive non-Hodgkin B-cell lymphomas. Among these patients, there were 21 (22%) patients with PBL (19 men and two women; median age: 45 years). Seven patients had PBL at their initial HIV diagnosis and 14 developed PBL after a median interval of 7.7 months of HIV diagnosis. Lymph nodes (n = 10), oral cavity/sinonasal mass (n = 6), and rectal masses (n = 5) were the common involved sites, and five of 15 (33%) had bone marrow involvement. Lymphoma cells were immunoreactive for MUM-1/IRF4 (100%), CD138 (90%), CD45 (63%), CD79a (47%), and CD30 (25%). Proliferation rate assessed by Ki67 was at least 90% in 18 of 20 cases. Eighteen patients received chemotherapy including etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (n = 13) and cyclophosphamide, doxorubicin, vincristine, and prednisone (n = 2). With a median follow-up time of 19 months, nine out of 17 patients died. Bone marrow involvement was associated with a poorer overall survival (median: 4.7 months, P = 0.015). CONCLUSION: PBL is the second most common type of aggressive lymphoma and often presents in lymph nodes of patients with poorly controlled HIV infection. Bone marrow involvement is associated with a poorer outcome.