From the archives of MD Anderson Cancer Center. Mesothelial/monocytic incidental cardiac excrescence with a review of the literature.

Mesothelial/monocytic incidental cardiac excrescence (MICE) is a rare benign lesion composed of monocytes and mesothelial cells that is most often encountered during cardiothoracic surgery. We describe a case in a 71-year-old man with known aortic valve stenosis who presented with gradual onset dyspnea over a few weeks, made worse with minimal exertion. A transesophageal echocardiogram revealed severe aortic stenosis and mild pericardial effusion. The patient underwent aortic valve replacement, coronary artery bypass, and amputation of the left atrial appendage. Histological examination of a 0.8 cm blood clot received along with the atrial appendage showed an aggregation of bland cells with features of monocytes associated with small strands and nodules of mesothelial cells, fat cells, fibrin and a minute fragment of bone. Immunohistochemical analysis showed that the monocytic cells were positive for CD4 and CD68 (strong) and negative for calretinin and keratin. By contrast, the mesothelial cells were positive for calretinin and keratin and negative for all other markers. In sum, the morphologic and immunohistochemical findings support the diagnosis of MICE. Based on our review of the literature, about 60 cases of MICE have been reported previously which we have tabulated. We also discuss the differential diagnosis.

Rare Lymphoma of the Breast: A Case Report.

Lymphoma of the breast is a rare malignancy of the breast lymphoid tissue. It can present as either a primary or a secondary malignancy due to metastasis from a systemic disease. Secondary breast lymphoma (SBL) is one of the most common malignancies to metastasize to the breast. Once present in the breast, these masses are often difficult to distinguish from primary breast carcinoma on both physical examination and diagnostic imaging modalities. Differentiating these tumors is imperative because each has a different management plan. This report presents a rare case of SBL in a 55-year-old Hispanic female and includes a review of its presentation, radiologic imaging findings, and management.

Pathological fracture due to primary bone lymphoma in a patient with a history of prostate cancer: A case report and review of literature.

Primary bone lymphoma (PBL) is a rare extranodal presentation within lymphomas and primary bone malignancies. Pathologic fracture (PF) is a common complication of metastatic bone disease but is, rarely, the presentation of a primary bone tumor. We report a case of an 83-year-old man with a history of untreated prostate cancer, presenting with atraumatic fracture of his left femur after months of intermittent pains and weight loss. Radiographic workup revealed a lytic lesion suspicious for PF secondary to metastatic prostate cancer; however, initial core biopsy results were inconclusive for malignancy. A complete blood count with differential and complete metabolic panel was within normal limits. During surgical fixation and nailing of the femur, a reaming biopsy was performed as a repeat measure and revealed diffuse large B-cell lymphoma. Staging with positron emission tomography and computed tomography found no evidence of lymphatic or visceral involvement and chemotherapy was promptly initiated. This case highlights the diagnostic workup challenges for PF secondary to PBL, especially in the setting of concurrent malignancy. Because of the non-specific presentation of a lytic lesion on imaging associated with atraumatic fracture, we highlight PBL as an important diagnostic consideration.

Primary splenic diffuse large B-cell lymphoma presenting as a splenic abscess.

Diffuse large B-cell lymphoma (DLBCL) arising in the spleen, also known as primary splenic DLBCL (PS-DLBCL), is a rare form of malignant lymphoma. It is defined as a lymphoma confined to the spleen or involving splenic hilar lymph nodes. Here we report a case of PS-DLBCL with CD30. The patient was a 62-year-old who presented with 2 weeks of left flank pain, chills, and abdominal distension. Computed tomography identified an 8-cm splenic mass with central necrosis interpreted as an abscess. A drain was placed, yielding purulent necrotic material; cytologically, only neutrophils were identified. However, purulent drainage continued for 28 days without resolution, prompting splenectomy. Pathological dissection revealed a multinodular mass with central necrosis. Microscopic examination revealed extensive karyorrhexis, abundant ghosts of large cells, and scattered large cells with pleomorphic, multilobated, and vesicular nuclei with moderately abundant cytoplasm. Immunohistochemical staining revealed large, atypical cells positive for CD20, CD30, CD45, PAX5, MYC (>40%), MUM1 (>30%), and p53 (focally). The large cells were negative for CD3 (polyclonal), CD4, CD5, CD8, CD10, CD15, CD34, BCL2, BCL6, AE1/AE3, S100, HHV8, and ALK. The Ki-67 proliferation rate was approximately 80% in large cells. Notably, this PS-DLBCL was positive for CD30, an unusual finding among non-Hodgkin B-cell lymphomas, which, coupled with the Reed-Sternberg-like morphology, raised the possibility of classic Hodgkin lymphoma. Therefore, we reviewed the literature to confirm the unique features of this large B-cell lymphoma, its abscess-like appearance, and its expression of CD30.

A Rare Case of CD4 Positive Cytotoxic PTCL, NOS With Leukemic Presentation.

Peripheral T-cell lymphoma, not otherwise specified (PTCL, NOS) is a relatively rare mature T-cell lymphoma that cannot be categorized under any of the well-defined category. This type of aggressive lymphoma mostly involves the lymph nodes, though any other organ can be affected. Leukemic presentation is extremely rare. No case report of isolated leukemic presentation was found after detail literature search. Herein we present a case of PTCL, NOS with leukemic presentation.

Liver Metastasis of Thymoma: Case Report and Review of the Literature.

The 2021 "World Health Organization (WHO) Classification of Thoracic Tumours" classifies epithelial tumors of the thymus (thymomas) based on cytomorphology. Thymomas with benign cytomorphology are classified as type A, AB, B1, B2, and B3, while those with malignant cytomorphology are classified as thymic carcinoma. Although all thymomas have malignant potential, extra-thoracic metastasis of thymomas is exceedingly rare and the exact incidence is not known. Literature review demonstrated 39 cases of thymoma with extra-thoracic metastases reported since the publication of the 1999 WHO Classification of Thoracic Tumours. Nine of these cases presented with metastasis to the liver in the setting of concurrent metastasis to other organs, while only three cases metastasized solely to the liver. We herein report a well-documented case of type B1 thymoma with relatively limited stage (IIb) with an isolated, single liver metastasis occurring seven years after primary resection in a patient with concomitant myasthenia gravis. The following report includes a review of the literature, a discussion of thymoma classification and its relevance to prognosis, and an overview of other extra-thoracic metastatic thymoma cases.

Recognition of a novel variant of phosphoglycerate kinase 1 deficiency PGK1 Galveston (c.472G > C) in a child with hemolytic anemia, neurologic dysfunction and myopathy.

The enzyme phosphoglycerate kinase 1 (PGK1) catalyzes the first ATP producing reaction in the glycolysis pathway. Certain mutations to the coding gene of PGK1 present clinically with varying manifestations including hemolytic anemia, central nervous system (CNS) dysfunction and myopathy. Various PGK1 mutations have been described in the literature at the clinical and molecular level. Herein, we describe a novel case PGK1 mutation (PGK1 Galveston) in a 4-year-old boy who presented with all three manifestations. We discuss the characteristic hematopathology findings from this patient as well as provide a comparison with previously described neuroimaging findings. The variable clinical presentation of this condition along with its inherent uniqueness provide a diagnostic challenge for physicians. This presentation will add to the current body of knowledge for this condition and help guide future investigation and management.

A rare case of complex variant translocation of t(9;22;16)(q34;q11.2;q24) in a newly diagnosed patient with chronic myeloid leukemia.

Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm associated with the dysregulated production of myeloid cells. The Philadelphia chromosome (Ph), t(9;22)(q34;q11), is a hallmark of the disease and found in 90-95% of diagnosed CML patients. The balanced, reciprocal translocation places the genes BCR and ABL1, next to each other, resulting in an increase of kinase activity. Additional cases involve complex variants, including translocation events involving an additional chromosome with the creation of the Ph chromosome. A rare three-way Ph chromosome complex variant, t(9;22;16)(q34;q11.2;q24), was identified in a 40-year-old female who presented with visual changes and leukocytosis. Cytogenetic analysis by G-banding revealed the presence of a three-way translocation involving the long arms of chromosomes 9, 22, and 16. Fluorescence in situ hybridization with a dual-color fusion probe confirmed the presence of the BCR::ABL1 fusion.

Angioimmunoblastic T-Cell Lymphoma: A Case Report.

Previously believed to be an exaggerated immune response and not a lymphoma, angioimmunoblastic T-cell lymphoma (AITL) is now recognized as a rare variant of peripheral T-cell lymphoma with an aggressive clinical course and poor response to current therapies. There is no standard of care for treatment, but the identification of extranodal involvement is useful for prognostic purposes since the involvement of more than one extranodal site can escalate the patient's risk category on the International Prognostic Index (IPI). Here we present the case of a patient with AITL who initially presented with an extranodal disease in the form of a fluorodeoxyglucose (FDG)-avid subcutaneous nodule and probable involvement of the spleen. After two months of treatment, her lymphoma exhibited an escalation of grade and an extensive worsening of Epstein-Barr virus (EBV) positivity.

Proposal of Diagnostic Approach of Periodontal Primary Non Hodgkin Lymphoma of Bone with Flow Cytometry as an Essential Diagnostic Component.

BACKGROUND: Primary bone lymphoma is a rare type of lymphoid neoplasm with favorable prognosis, where Primary Non Hodgkin Lymphoma of bone (PB-NHL) is most common with the subtype. Amongst PB-NHL, diffuse large Bcell lymphoma represents the majority of cases. The mandible is a very uncommon site of involvement, presenting as a painful bone mass with high suspicion of osteomyelitis. METHODS: We report the case of a 45-year-old male with no significant past medical history who was admitted to the hospital with a large right jaw mass and pain after recent tooth removal. The original tissue biopsy was not diagnostic, and cultures were found to be negative for microorganisms. Due to enlargement of the mass, a fine needle aspiration (FNA) was done. At the time of rapid onsite evaluation of the FNA, atypical lymphoid cells were seen, and material was obtained for flow cytometry (FC) evaluation. This revealed an aberrant clonal B-cell population. The consequent immunohistochemical evaluation of original material supported the diagnosis of PB-NHL. After chemotherapy patient improved. RESULTS: After an extensive English language literature review, we identified and summarized the clinical presentations, diagnostic procedures, histopathologic features, treatment methods, and outcomes of forty-two cases of periodontal PB-NHL. Based on our findings, we propose a set of clinical features at initial presentation to increase the clinical suspicion of periodontal PB-NHL for practitioners. CONCLUSION: Based on our institution's experience and the literature review conclusions, we propose the University of Texas Medical Branch diagnostic approach for PB-NHL and suggest that FNA and FC should be utilized as the essential diagnostic component. The fast and efficient diagnosis of PB-NHL can facilitate the correct treatment and sufficiently improve patient care.

Quantitative imaging for development of companion diagnostics to drugs targeting HGF/MET.

The limited clinical success of anti-HGF/MET drugs can be attributed to the lack of predictive biomarkers that adequately select patients for treatment. We demonstrate here that quantitative digital imaging of formalin fixed paraffin embedded tissues stained by immunohistochemistry can be used to measure signals from weakly staining antibodies and provides new opportunities to develop assays for detection of MET receptor activity. To establish a biomarker panel of MET activation, we employed seven antibodies measuring protein expression in the HGF/MET pathway in 20 cases and up to 80 cores from 18 human cancer types. The antibodies bind to epitopes in the extra (EC)- and intracellular (IC) domains of MET (MET4EC, SP44_METIC, D1C2_METIC), to MET-pY1234/pY1235, a marker of MET kinase activation, as well as to HGF, pSFK or pMAPK. Expression of HGF was determined in tumour cells (T_HGF) as well as in stroma surrounding cancer (St_HGF). Remarkably, MET4EC correlated more strongly with pMET (r = 0.47) than SP44_METIC (r = 0.21) or D1C2_METIC (r = 0.08) across 18 cancer types. In addition, correlation coefficients of pMET and T_HGF (r = 0.38) and pMET and pSFK (r = 0.56) were high. Prediction models of MET activation reveal cancer-type specific differences in performance of MET4EC, SP44_METIC and anti-HGF antibodies. Thus, we conclude that assays to predict the response to HGF/MET inhibitors require a cancer-type specific antibody selection and should be developed in those cancer types in which they are employed clinically.

Neoadjuvant dasatinib for muscle-invasive bladder cancer with tissue analysis of biologic activity.

OBJECTIVES: Preclinical urothelial carcinoma models suggest activity of dasatinib, an oral SRC-family kinase (SFK) inhibitor. We sought to determine the feasibility and biologic activity of neoadjuvant dasatinib (Neo-D) in patients with muscle-invasive urothelial carcinoma of the bladder (miUCB) preceding radical cystectomy (RC). MATERIALS AND METHODS: A prospective multisite phase II trial was conducted. Key eligibility criteria included: resectable miUCB (T2-T4a, N0, M0), and Eastern Cooperative Oncology Group performance status 0 to 1. Patients received oral Neo-D 100mg once daily for 28±7 days followed by RC 8 to 24 hours after the last dose. The primary end point was feasibility, defined as≥60% of patients with miUCB completing therapy without treatment-related dose-limiting toxicity (DLT). Pre- and posttreatment tumor immunohistochemistry of phosphorylated SFK (pSFK), Ki-67, and cleaved caspase (Cas)-3 results were analyzed by paired t test. RESULTS: The study completed full accrual with enrollment of 25 patients of whom 23 were evaluable for feasibility. The study achieved its primary end point with 15 patients (65%) completing therapy without treatment-related DLTs. DLTs included: fatigue (n = 2), pulmonary embolism, abdominal pain, supraventricular tachycardia, enteric fistula, hematuria, and dyspnea (n = 1 each). At RC, 5 patients (23%) had

Hemangioendothelioma of soft tissue: Cytological dilemma in two cases at unusual sites.

Hemangioendothelioma is a rare vascular tumor of intermediate malignancy. Cytologically, it can simulate a non-vascular malignant tumor. We report two cases of this tumor, which were misdiagnosed at cytology. In the first case, a 27-year-old man presented with an anterior abdominal wall tumor. Fine needle aspiration cytology (FNAC) of the tumor showed polygonal cells with vacuolated cytoplasm in clusters having moderate nuclear atypia in a background of necrosis. A diagnosis of metastatic carcinoma was made. The histological examination showed features of epithelioid hemangioendothelioma. In the second case, a 13-year-old female child presented with unilateral enlargement of the right tonsil. At ultrasound-guided FNAC, a diagnosis of, 'small round cell tumor, could be consistent with alveolar rhabdomyosarcoma,' was made. The histological examination showed features of papillary intralymphatic angioendothelioma (Dabska's tumor). We conclude that epithelioid hemangioendothelioma should be considered in the differential diagnosis of metastatic carcinoma and small round cell tumor even at unusual sites.

Encapsulated follicular variant papillary thyroid carcinoma: problems in histological diagnosis.

Thyroid neoplasms are the commonest endocrine neoplasms and account for the most number of thyroidectomies done. Encapsulated thyroid lesions are being encountered more commonly in thyroidectomy specimens in recent time. The present study was undertaken to analyse the incidence of thyroid malignancies with a changing pattern and to discuss the difficulties encountered in histopathological interpretation of encapsulated neoplastic lesions of follicular cell origin. It is a retrospective study done in the department of pathology, NRS Medical College, Kolkata. Data of all the thyroidectomy specimens examined over last four years (August 2006 to July 2010) were retrieved and slides were reviewed. All slides of thyroid lesion received in the department of pathology, NRS Medical College for review were also included in this study. Frequency distribution study was done with the sample analysed. Follicular variant of papillary carcinoma was the commonest type of thyroid malignancy, on review, with the encapsulated sub-variant exceeding the diffuse type. This variant is a diagnostic challenge because it has to be differentiated from other encapsulated follicular thyroid lesions, especially follicular adenoma. The data analysis, results and problems in the diagnostic protocols are discussed in this study along with review of literature. Reclassification of thyroid tumour may be warranted in future with this background.

Pseudothrombocytopenia -- a caveat.

Pseudothrombocytopenia is an ex vivo thrombocytopenia, counted by an automated cell counter, but not configured by microscopic examination of a well prepared blood smear. Incidences of pseudothrombocytopenia reported in different studies range from 0.09-0.21%, which could account for 15-30% of all cases of thrombocytopenla. Failure to identify pseudothrombocytopenia has led to a lot of clinical problems like unnecessary platelet transfusion, glucocorticoid therapy and so on. Haematological cell counters count platelets as particles with volume between 2 and 20fl. Thus platelet clumps are counted as leucocytes while fragmented RBCs as platelets. This study found pseudothrombocytopenia due to causes like EDTA blood stored at less than 32 degrees C for more than 2 hours (35%), excess EDTA in sample (10.7%), hyperlipidaemia, auto-immune disease, pregnancy, etc. No apparent cause could be found in 52% of cases. Hence it is emphasised that direct microscopic examination of a well stained blood smear from EDTA-venous blood (within 1hour) and or direct counting under Neubauer chamber with 1% ammonium oxalate (in special cases) is almost mandatory before releasing a report of platelet count. Also factors related to ratio and storage of EDTA-blood, calibration of instruments, proper selection of reagents, supervision of laboratory staff are essential to rule out any error of report including pseudothrombocytopenia.