Panel Of Immunohistochemical Stains Research Articles

GATA3 Expression in Solid Vimentin-Negative Eosinophilic Renal Epithelial Tumors-A Comprehensive Study of 48 Tumors.

Vimentin-negative solid eosinophilic renal tumors, such as renal oncocytoma, chromophobe renal cell carcinoma (chromophobe RCC), low-grade oncocytic tumor (LOT) of the kidney, and eosinophilic vacuolated tumor (EVT), often present diagnostic challenge to pathologists as they can have significant morphologic overlap. Recent studies have shown that the LOT is consistently positive for GATA3. To test the utility of GATA3 in this potentially challenging diagnostic setting, we investigated GATA3 expression in 48 vimentin-negative solid eosinophilic renal tumors with unequivocal diagnosis, which included 19 LOTs, 3 EVTs, 12 chromophobe RCCs, 11 renal oncocytomas (ROs), and 3 FLCN-mutated renal tumors. GATA3 was at least focally positive in 89% of the LOTs (17/19), 67% of the EVTs (2/3), and 33% of the chromophobe RCCs (4/12) and was negative in all ROs (0/11) and FLCN-mutated renal tumors (0/3). Our study shows that GATA3 can be useful in differentiating between LOT and RO, but it can be focally positive in many tumors of EVT and chromophobe RCC. Therefore, GATA3 could be useful as a panel of immunohistochemical stains that are used in diagnostic algorithm of vimentin-negative solid eosinophilic renal tumors. However, one should not solely rely on GATA3 as vimentin-negative solid eosinophilic renal tumors can have overlapping GATA3 expression.

PAX5 and CD70 are expressed in thymic carcinoma but not in atypical thymoma (WHO type B3 thymoma): an immunohistochemical analysis of 60 cases

AimsThymic carcinoma and atypical thymoma (WHO type B3 thymoma) are unusual tumours the separation of which may be challenging in small biopsies. Both tumours consist of epithelioid tumour cells that...

Primary Mast Cell Sarcoma of the Maxillary Sinus and Gingiva Mimicking Malignant Neuroendocrine Tumor: A Case Report

Mast cell sarcoma (MCS) is an extremely rare and aggressive malignancy primarily affecting bones, with limited literature associating it with neuroendocrine marker expression. This report presents a rare case of MCS arising in the maxillary sinus and gingiva. A 74-year-old man presented with a progressively enlarging ulcer on the right-sided upper gingiva. Magnetic resonance imaging revealed a 3.4 cm tumor on the floor of the right maxillary sinus. The patient underwent an inferior maxillectomy and right-sided neck dissection. Microscopically, the tumor consisted of monotonous round cells with oval nuclei, vesicular chromatin, inconspicuous nucleoli, and brisk mitoses. A panel of immunohistochemical stains was initially applied to exclude common sinonasal undifferentiated neoplasms, such as sinonasal undifferentiated carcinoma, melanoma, rhabdomyosarcoma, Ewing sarcoma, and lymphoma. The tumor cells showed patchy staining for INSM1 and synaptophysin, but were negative for AE1/AE3, CAM5.2, p40, chromogranin, S100, HMB45, NKX2.2, desmin, CD45 (LCA), CD3, and CD20, with intact INI1 and BRG1 expression. No specific diagnosis could be rendered based on the staining results, leading to consideration of other rare malignancies. Additional staining revealed positivity for CD117, mast cell tryptase, CD13, CD33, CD43, and CD68, confirming the MCS diagnosis. Molecular testing for KIT mutation was negative. Subsequent bone marrow biopsy demonstrated infiltration of atypical mast cells, which led to a diagnosis of mast cell leukemia. Despite high-dose chemotherapy, the patient died three months after the initial diagnosis. The undifferentiated epithelioid morphology and unusual aberrant neuroendocrine marker expression posed significant diagnostic challenges. The major differential diagnoses were discussed in this report.

Hepatic and perihepatic PEComas: A study describing a series of five rare cases.

Perivascular epithelioid cell tumors (PEComas) encompass a group of rare mesenchymal neoplasms, with dual melanocytic and muscular differentiation. Hepatic PEComas are rare and difficult to diagnose, and their behavior is still unclear. Herein, we report a total of five cases of hepatic and perihepatic PEComas over a period of the last 5 years from our and collaborating center's archive. A detailed histological evaluation was done. A comprehensive panel of immunohistochemical stains was used and fluorescence in-situ hybridization analysis was performed for the TFE3 gene using break-apart probes. All these patients were women, with an average age of presentation of 44 years. The lesions were in the right hepatic lobe: three cases, the left hepatic lobe: one case, and gastrohepatic ligament: one case. The preoperative clinicoradiological diagnoses were hepatocellular carcinoma (HCC), focal nodular hyperplasia, hemangioma, metastasis, and gastrointestinal stromal tumor, respectively. Surgical excision was performed in four cases with no further adjuvant therapy. Histopathological examination and subsequent immunophenotyping revealed a diagnosis of PEComa. Fluorescence in-situ hybridization analysis was performed for TFE3 gene rearrangement in four cases. This series highlights the fact that accurate histological diagnosis of hepatic or perihepatic PEComas is important to prevent unnecessary aggressive treatment, unlike primary hepatocellular carcinomas or hepatoid/epithelioid metastatic tumors.

Immunohistochemical expression of vimentin, E-cadherin, and CD45 in natural cases of canine cutaneous round tumors.

Round cell tumors are common cutaneous lesions in dogs, with increased occurrence percentages among different skin tumors. This study aimed to investigate the frequency as well as gross and pathological characteristics of round cell tumors in natural cases of tumorous dogs in relation to breed, sex, and age. Moreover, it aimed to evaluate the immunohistochemical expression of a panel of immunohistochemical stains, including vimentin, E-cadherin, and cluster of differentiation (CD45) as an adjunct technique for the differential diagnosis of cutaneous round cell neoplasm. Data were collected from 64 dogs of both sexes (36 females and 28 males), various breeds, and different ages (8 months to 7 years). The histopathological nature of neoplastic growth was reported, and neoplasm prevalence was classified using age, sex, breed, and site on the body. We observed 48 cases of transmissible venereal tumors, 12 cutaneous histiocytomas, and 4 histiocytic sarcoma. Immunohistochemical characterization revealed an intense positive immunoreactivity for vimentin in transmissible venereal tumor cells and moderate positive immunoreactivity for E-cadherin and CD45 in cutaneous histiocytoma and histiocytic sarcoma cells. In conclusion, the canine transmissible venereal tumor was the most frequent form of round cell tumor; thus, a definitive cutaneous neoplasm diagnosis should be based on histopathological morphology and immunohistochemical findings.

Giant cell tumor of the clivus misdiagnosed as calcifying fibrous tumor

Abstract Introduction/Objective Giant cell tumors of bone (GCTs) are generally benign, locally aggressive lesions accounting for approximately 4% of primary bone tumors. GCTs of the skull are rare and constitute <1% of all reported GCTs as they typically occur in the epiphysis of long bones. Specifically, in the clivus location, these tumors are exceedingly rare with fewer than 10 articles in English literature. The purpose of this report is to describe a case of GCT in this unusual location that was misdiagnosed as giant cell reparative granuloma on biopsy and subsequently calcifying fibrous tumor on resection. Methods/Case Report A 34-year-old male presented with history of headache, visual disturbance, epistaxis, and nausea. MRI demonstrated a large soft tissue mass eroding the clivus. A biopsy was interpreted at an outside institution as giant cell reparative granuloma. The patient was treated with denosumab and subsequently underwent resection of the mass due to worsening symptoms. Post-treatment pathology was interpreted as calcifying fibrous tumor. The patient presented to our institution for further management and outside pathology was reviewed. Histologically, the initial tumor was composed of a bland spindle cell proliferation with admixed osteoclast-type giant cells. In this location, the differential diagnosis includes Brown tumor, giant cell reparative granuloma, and, rarely, GCT. HG34W immunostain was positive in the tumor cells confirming the diagnosis of GCT. The post-therapy specimen showed abundant woven bone formation and a lack of giant cells. Post-denosumab GCT are known to show these features. Follow up imaging showed a slow growing moderately enhancing mass at the resection site. Patient is alive with disease 36 months after initial diagnosis. Results (if a Case Study enter NA) NA Conclusion With rare exceptions, bone tumors frequently follow generalized patterns of involvement. Pathologists need to be aware of these exceptions. Appropriate panel of immunohistochemical stains help clinching the right diagnosis, especially in unusual clinical settings.

Immunoreactivity of Histiocytes to OCT4; a diagnostic pitfall

Abstract Introduction/Objective Immunohistochemical stains are supposed to make a Pathologists’ life easier; however, interpretation of some stains in isolation can be a diagnostic pitfall. Immunoreactivity of paraganglia to OCT4 stain is a known pitfall for this stain when evaluating retroperitoneal lymph node dissection specimens for germ cell tumour metastasis. The purpose of this report is to highlight another pitfall of the OCT4 stain, albeit in a similar clinical scenario. Methods/Case Report A 49-year-old male with a history of left testicular seminoma metastatic to periaortic, retroperitoneal and left supraclavicular lymph nodes, status post orchiectomy and chemotherapy, presented with a rising B-HCG and PET scan evidence of recurrent/refractory disease. His imaging showed interval increase in FDG uptake of left periaortic lymph nodes despite a decrease in size. A biopsy was performed. Pathologic evaluation showed predominantly necrotic tissue with rare clusters of atypical cells with clear to pink cytoplasm, monotonous nuclei, and rare admixed lymphocytes. Immunohistochemical stains showed the atypical cells to be positive for OCT4 stain, raising the possibility of viable seminoma. However, additional satins showed the cells to be positive for CD68 and CD163, and negative for CD117, SALL-4, pancytokeratin, SF-1, GATA3 and synaptophysin. Therefore, the atypical cells were interpreted to represent histiocytes; no viable germ cell tumor was identified. Results (if a Case Study enter NA) NA Conclusion This case highlights the importance of using a panel of immunohistochemical stains, instead of relying on one stain, even if the stain is thought to be fairly specific. Pathologists need to be aware of immunoreactivity of histiocytes to OCT4 as a potential diagnostic pitfall in addition to the paraganglion cells staining for OCT4 being a pitfall.

Acute myeloid leukemia with monocytic differentiation (myeloid sarcoma) masquerading as bone-soft tissue malignancy

Abstract Introduction/Objective Myeloid sarcoma is an extramedullary solid neoplasm composed of myeloid precursors with or without maturation. This tumor usually occurs simultaneously or following the onset of acute leukemia. Rarely, it can be the first manifestation of acute myeloid leukemia. We report a case of this rare tumor presenting histologically as a bone sarcoma with features of extraskeletal myxoid chondrosarcoma and myoepithelial carcinoma Methods/Case Report A 76-year-old female was referred to our institution for evaluation of a right foot mass associated with pain and swelling. MRI showed a 2.4 x 1.5x 1.2 cm soft tissue mass along the lateral margin of proximal and mid diaphysis of first metatarsal. The clinical and radiologic differential diagnosis was primary bone-soft tissue malignancy, or infection. Histologically, the biopsies showed sheets and cords of cells in a myxoid background. Cytologically the cells were plasmacytoid, mononuclear, mitotically active with immature chromatin, prominent nucleoli, and moderate to abundant cytoplasm. This morphologic appearance elicited the differential diagnosis of extraskeletal myxoid chondrosarcoma, myoepithelial carcinoma, and plasmacytoma. An initial panel of immunohistochemical stains showed the lesional cells to be negative for S-100, SOX-10, pancytokeratin, desmin, p63, EMA, CAM5.2, and CD138 but positive for CD43. Additional immunohistochemistry showed diffuse reactivity for CD33, and lysozyme; CD163 was focally positive, and the cells were negative for CD20, CD3, CD30, CD99, MUM1, CD138, and CD34. A diagnosis of extramedullary acute myeloid leukemia with monocytic differentiation (myeloid sarcoma) was rendered. Subsequently, patient underwent bone marrow biopsy which showed involvement by acute myeloid leukemia with monocytic differentiation. Results (if a Case Study enter NA) NA Conclusion Myeloid sarcoma is a rare tumor and presentation as an isolated metatarsal mass is highly unusual and exceedingly rare. This can mislead clinicians, radiologists, and pathologists. Pathologists need to keep hematopoietic tumors in their differential diagnosis even when the anatomic sites as well as the morphology are not typical of hematopoietic malignancies.

Expression of TLE1 in a Carcinoid Tumor of the Lung With Spindle Cell Morphology-A Potential Diagnostic Pitfall.

Tumors of the lung with a spindle cell morphology require consideration of many entities in the differential diagnosis, including metastases. Ancillary immunohistochemical stains but also molecular studies are typically required to arrive at the proper diagnosis. We present a case of a 71-year-old woman with multiple lung nodules, mediastinal lymphadenopathy, and a history of uterine cancer who underwent endobronchial ultrasound-guided fine needle aspiration and biopsy of the lung and mediastinal lymph nodes. A sampling of the lung lesion showed a cytologically bland neoplasm with spindle cell morphology, lacking necrosis or brisk mitotic activity. In conjunction with the cytomorphology, strong and diffuse Transducin-like enhancer of split 1 (TLE1) reactivity in the tumor cells initially raised the diagnosis of synovial sarcoma; however, subsequent results of additional testing showed strong and diffuse expression with AE1/AE3, CK 8/18, TTF-1, synaptophysin and chromogranin and focal or negative staining with a large number of other antibodies. This warranted a diagnosis of a carcinoid tumor. This is the first report of TLE1 staining in a carcinoid tumor of the lung. Therefore, when evaluating tumors of the lung with spindle cell morphology in which the differential diagnosis may include both carcinoid tumor and synovial sarcoma, TLE1 expression should be interpreted with caution and in conjunction with an expanded immunohistochemical staining panel.

Clinicopathologic and Immunophenotypic Classification of Invasive Lobular Carcinoma with Histiocytoid Features.

Histiocytoid lobular breast carcinoma is a rare subtype of invasive lobular carcinoma characterized by relatively bland, uniform nuclei, single small eosinophilic nucleolus, and ample granular cytoplasm. These cancers are typically triple negative, show frequent androgen receptor (AR) positivity, and are therefore theorized to represent a variant of apocrine differentiation in invasive lobular carcinoma. Anecdotal evidence suggests that these tumors have excellent outcomes, though some studies suggest a variable clinical outcome. Inclusion criteria included women with a histologic diagnosis of invasive lobular carcinoma with histiocytoid features, regardless of immunohistochemical profile, diagnosed at our institution between 2008 and 2021 with additional tissue still available for ancillary studies. We reviewed patients meeting these criteria and investigated hematoxylin and eosin-stained slides and a panel of immunohistochemical stains (estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2 [HER2], AR, endothelial growth factor receptor, and keratin 5/6), as well as outcomes including survival and metastatic disease. Overall, 12 eligible patients were identified. The classical immunophenotype (triple negative with AR positivity) was noted in 4 out of 12 tumors. The majority of the remaining tumors (7 out of 12) showed a luminal B immunohistochemical profile, while 1 out of 12 was HER2-enriched. No patients in the cohort died from disease-related causes and 2 out of 12 presented with distant metastatic disease during their disease course. Histiocytoid lobular breast carcinoma is a morphologic variant of lobular carcinoma with apocrine features that shows a variable immunohistochemical profile and variable clinical behavior. Further subclassification and stricter diagnostic criteria may be helpful in the distinction between truly indolent tumors and those with more aggressive clinical features.

High-grade Serous Carcinoma can Show Squamoid Morphology Mimicking True Squamous Differentiation.

Tubo-ovarian high-grade serous carcinoma (HG-SC) and ovarian endometrioid carcinoma (EC) can show overlapping morphologic features, such as glandular and solid patterns. The differential diagnosis of these subtypes is thus sometimes difficult. The existence of "squamous differentiation" tends to lead to a diagnosis of EC rather than HG-SC. We noticed that HG-SC can contain a "squamoid component," but its nature has been poorly investigated. This study was thus established to clarify the nature of this "squamoid component" in HG-SC by investigating its frequency and immunohistochemical features. We reviewed hematoxylin and eosin-stained slides of 237 primary untreated cases of tubo-ovarian HG-SC and identified 16 cases (6.7%) of HG-SC with "squamoid component." An immunohistochemical staining panel (CK5/6, CK14, CK903, p40, p63, WT1, ER, and PgR) was used to analyze all of these 16 cases. We also selected 14 cases of ovarian EC with "squamous differentiation" as a control. The "squamoid component" in HG-SC was completely p40-negative and showed significantly lower expression of CK5/6, CK14, CK903, and p63 than the "squamous differentiation" in EC. The immunophenotype of the "squamoid component" in HG-SC was concordant with the conventional HG-SC component (WT1-positive/ER-positive). Furthermore, all 16 tumors were confirmed to be truly "HG-SC" by the findings of aberrant p53 staining pattern and/or WT1/p16 positivity, and the lack of mismatch repair deficiency and POLE mutation. In conclusion, HG-SC can on rare occasions show a "squamoid component" mimicking "squamous differentiation." However, the "squamoid component" in HG-SC does not represent true "squamous differentiation." The "squamoid component" is one part of the morphologic spectrum of HG-SC, which should be interpreted carefully for the differential diagnosis of HG-SC and EC. An immunohistochemical panel including p40, p53, p16, and WT1 is a useful adjunct to achieve a correct diagnosis.

The Pathologic Diagnosis of Pediatric Soft Tissue Tumors in the Era of Molecular Medicine: The Sarcoma Pediatric Pathology Research Interest Group Perspective.

Pediatric soft tissue tumors are one of the areas of pediatric pathology that frequently generate consult requests. Evolving classification systems, ancillary testing methods, new treatment options, research enrollment opportunities, and tissue archival processes create additional complexity in handling these unique specimens. Pathologists are at the heart of this critical decision-making, balancing responsibilities to consider expediency, accessibility, and cost-effectiveness of ancillary testing during pathologic examination and reporting. To provide a practical approach to handling pediatric soft tissue tumor specimens, including volume considerations, immunohistochemical staining panel recommendations, genetic and molecular testing approaches, and other processes that impact the quality and efficiency of tumor tissue triage. The World Health Organization Classification of Soft Tissue and Bone Tumors, 5th edition, other recent literature investigating tissue handling, and the collective clinical experience of the group are used in this manuscript. Pediatric soft tissue tumors can be difficult to diagnose, and evaluation can be improved by adopting a thoughtful, algorithmic approach to maximize available tissue and minimize time to diagnosis.

Germ Cell Tumors of the Ovary: A Review.

Ovarian germ cell tumors are a diverse group of benign and malignant neoplasms that occur in a wide age range, but with a predilection for younger age group. The majority are represented by the frequently encountered mature cystic teratomas. Malignant germ cell tumors are uncommon, and in some cases have a characteristic clinical presentation. However, from a histologic standpoint these tumors can sometimes be challenging to diagnose due to overlapping morphology with epithelial, and in some cases sex cord tumors. In these cases, a panel of immunohistochemical stains often facilitates the correct diagnosis. This review article discusses the clinicopathologic findings and pertinent ancillary studies of both common and uncommon germ cell tumors of the ovary.

Identification of Nodular Lymphocyte-Predominant Hodgkin Lymphoma Variant Morphology Using Artificial Intelligence

Background Lymphocyte predominant (LP) cells located outside B-cell-rich nodules are the hallmark of variant morphologic patterns of nodular lymphocyte predominant Hodgkin lymphoma (NLPHL). In comparison with typical NLPHL (patterns A and B), cases with variant morpholoy (patterns C, D, E and F) are associated with significantly worse clinical behavior. Nevertheless, assessment of tissue architecture may be challenging in limited biopsy specimens, which are increasingly common in routine clinical practice. We sought to address this gap by developing artificial intelligence-assisted modules to accurately recognize NLPHL and distinguish patterns A/B from variant patterns, namely the most common of those, pattern C. Material & Methods The study group included whole slide images (WSI) of hematoxylin and eosin (H&E) stains and CD20 immunohistochemistry stains from 10 NLPHL patients; cases emcompassed patterns A, B & C (A/B: 5 cases; C: 5 cases) as determined by hematopathology review. We designed modules to assess the spatial relationship between LP cells and B cell-rich areas by first seeking to detect LP cells using high-power field (HPF) magnification of H&E WSI (Figure A1). We split the WSI into tiles (8000 x 8000 pixels) to mitigate the computational burden of WSI analysis. For each tile, we deployed the pretrained HoVer-Net for nuclear segmentation. To distinguish LP cells from surrounding small lymphocytes, we analyzed nuclear size, intensity, and gray-level co-courrance matrix (GLCM) features (correlation and dissimilarity). For each feature, we identified the optimal threshold based on feature histogram of LP in comparison to the remainder surrounding cells. Nuclei meeting all feature criteria were labeled as LP cells and validated morphologically by hematopathologists. All tiles were then stitched to illustrate the spatial distribution of LP cells on WSI. Next we deployed the active contour (AC) technique, an iterative region-growing image segmentation algorithm, to identify B-cell areas from CD20 stains (Figure A2). To reliably define the intial contours for the AC, we abided by the following criteria: 1) Red (R) channel intensity larger than both the green (G) and blue (B) channels, with a ratio of 1.25; 2) Including pixels in the bottom 10% of the intensity histogram after removal of slide background and converting the RGB image into gray scale. We merged the contours from these two techniques and used them as initial seeds for AC segmentation, after which we took the final evolved contour as the boundaries of B-cell areas. We then overlayed CD20 on H&E WSI to assess the spatial relationship between the detected LP cells and B-cell areas. Since tissue sections on the CD20 and H&E slides represent neighboring slices, only translation, rotation, and slight scaling were surmised to occurr between slides in this pilot study set. Accordingly, we employed the affine registration paradigm and optimized mutual information between the transformed CD20 and fixed H&E images until convergence then warped the detected B-cell areas via the obtained deformation field (Figure A3). Results The concordant positioning between two stains after registration allowed us to compare the spatial relationship of LP cells to B-cell areas (including assessment of the number of LP cells inside (922) and outside (639) B-cell areas) (Figure A4). We then segmented the final image into quadrants to simulate needle core biopsies and confirmed the efficiency of our modules in detecting LP cells and analyzing their relationship to B-cell areas in limited tissue, in all quadrants (Figure A5). Our model was successfully applied on 100% of 10 NLPHL cases in this pilot group. After proof of concept was established in a full tissue biopsy sample (Figure A1-5), we applied the same steps to an actual physical needle core biopsy of an NLPHL-pattern C case (Figure B1-3) and were able to identify 7 out of 29 LP cells located outside B-cell areas, in congruence with the previously rendered diagnosis (Figure B4). Conclusion This technique, using H&E staining and CD20 immunohistochemistry only, is especially promising to work-up cases when ordering a routine panel of immunohistochemical stains is not feasible due to limited tissue that may be exhausted. Further validation using an independent cohort is warranted in the future. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

S2691 A Rare Presentation of Gastric Plastocytomas in a Patient With Multiple Myeloma

Introduction: Multiple myeloma is an uncommon hematological neoplasm. This malignancy involves unchecked plasma cell growth in the bone marrow, but in a subset of often more advanced cases, these cells may migrate to soft tissues causing extramedullary plasmacytoma. This is unusual, and, in the literature, few cases of extramedullary plasmacytomas involve the gastrointestinal tract. Within this system, the more common locations are the stomach, the liver, the large bowel, and more rarely, the small bowel. Case Description/Methods: A 59-year-old male with a medical history of chronic hepatitis C, and Stage III multiple myeloma status post four cycles of chemotherapy presented with altered mental status. Upon evaluation, he had significant electrolyte abnormalities, remarkable anemia, severe renal and liver dysfunction, and a positive hemoccult test. Our patient received intravenous fluid, and multiple blood products. He was then admitted to the intensive care unit for a high level of care. On the second day of admission, he developed new onset hematemesis, and the gastroenterology team was consulted. The patient was started on a pantoprazole drip. Urgent esophagogastroduodenoscopy showed several polypoid appearing masses with overlying ulceration in the gastric fundus (Figure a &b), and tissue biopsies were obtained. Biopsy result of the polypoid fundal mass showed a large cell neoplasm with plasmocytic differentiation. Gastric tissue sections showed an ulcerated lesion with submucosal, tightly packed atypical large cells with multinucleation, prominent nucleoli and relatively identifiable mitoses (Figurec). A panel of immunohistochemical stains with plasma cell markers were positive for kappa, Multiple Myloma-1 nuclear protein, and CD138 (Figure d-f). The overall findings were compatible with gastric involvement by a plasma cell neoplasm. Discussion: This case highlights a complicated, yet a uniquely rare presentation of extramedullary plasmacytoma in a patient diagnosed with multiple myeloma. Although the gastrointestinal tract is rarely involved in patients with multiple myeloma, it should be considered as the differential diagnosis in patients with gastrointestinal bleeding especially with a known concurrent systemic hematological malignancy. The presence of gastrointestinal involvement and the malignant phase of multiple myeloma are associated with a poor prognosis despite aggressive therapy, and it is therefore paramount to establish an accurate diagnosis early to avoid any delays in treatment.Figure 1.: (a,b) EGD shows polypoid EMP in the gastric fundus. (c) Infiltration of plasmablasts with highly atypical nuclei and prominent nucleoli (hematoxylin-eosin 20x). (d) Granular positivity for kappa immunoglobulin light chain. (e) Positive immunostaining for MUM-1. (f) Positive CD138 immunostaining highlights the plasma cells in the lamina propria of the gastric fundus EMP.

Clinicopathological characteristics and immunophenotype of six cases of cardiac myofibroblastic sarcoma in a single tertiary hospital, Philippine Heart Center, from 2000 to 2018

Myofibroblastic sarcoma (MS) is a rare malignant tumor of myofibroblast. Myofibroblasts were primarily described by Gabbiani et al. by means of electron microscopy. These spindle cells have features common with smooth muscle cells and fibroblast. Vasudev et al. first reported the pathologic characteristics of MS in 1978. Mentzel et al. coined the term “low-grade MS” after immunohistochemical and ultrastructural profiling in a series of cases. This study was undertaken to analyze the clinicopathologic, histopathologic, and immunohistochemical characteristics of MS cases arising in the heart.
 This is a descriptive study performed at the Philippine Heart Center. All twelve cases diagnosed as cardiac MS and other cardiac spindle cell tumors included in the Philippine Heart Center Pathology Cardiac Registry from 2000 to 2018 were reviewed. Six of the twelve cases were later proven or reclassified as MS.
 The six patients with MS were composed of three males (50%) and three females (50%) with a mean age of 57.5 and SD of 9.91. Four of the cases were from the left atrium (68%), one was from the right atrium (16%), and one was biatrial (16%). The tumor size ranged from 3.0 to 8.7 cm with a mean size of 5.57 cm and SD of 1.60. All six cases were treated surgically; four by excision (68%), one by debulking (16%), and one by both excision and debulking (16%). Histologically, the six tumors were predominantly composed of pleomorphic to monomorphic spindle cells arranged in syncytium, storiform, fascicles, and dense cellular sheets, some are intersecting at angles. The individual tumor cells are spindled with elongated nuclei with blunted ends, granular to open chromatin pattern, inconspicuous nucleoli, and scanty to moderate amount of eosinophilic to amphophilic cytoplasm. Cytoplasmic membrane are indistinct. Lymphoplasmacytic infiltrates are present with a mean of 28.67 per 10 high power fields, range of 7-91, and SD of 33.07. Mitosis are present with a mean of 12.17 per 10 high power fields, range of 3-32, and SD of 10.93. Necrosis of less than 50% is present in 4 of 6 cases (67%). Two cases (33%) showed no necrosis. Trichrome stain showed collagen deposits in five of six cases (83%). Immunohistochemically, all six cases of MS showed reactivity for vimentin and smooth muscle actin (100%). Three of six cases were reactive to calponin (50%). All six cases show non-reactivity against h-caldesmon (0%). Two of the six cases were reactive with desmin (33%). Two of the six cases were reactive with CD99 (33%). Only one of six cases were reactive to pancytokeratin (17%). No significant differences between proliferation indices using Ki-67 and p53 were observed.
 The application of the panel of immunohistochemical stains can aid in the diagnosis of MS in particular h-caldesmon which when negative rules-out smooth muscle tumors. MS consistently expresses vimentin and smooth muscle actin. Expression of calponin, desmin, and CD99 is variable. Prognostic value of proliferation indices using Ki-67 and p53 as a prognostic indicator is not proven.

Minimally Invasive Endoscopic Treatment of Gastric Leiomyosarcoma: A Rare Case Report and Review of Literature

Background Since the c-kit was described in 1998, gastrointestinal LMS remains a relatively rare disease in the post-GIST era. Previous studies have reported that gastric LMS accounts for only 1% of gastric tumors. This report provides valuable endoscopic and endoscopic ultrasound data for rare diseases such as primary gastric leiomyosarcoma, which can add experience for clinical diagnosis to the current literature. Particularly, this case proved that the early-stage lesions can be treated with minimally invasive endoscopic treatment with high safety, good tolerance, and satisfactory clinical results. Case Presentation A 63-year-old female patient visited our hospital mainly because of “epigastric pain and discomfort for 2 months.” After hospitalization, the relevant examinations were performed, and laboratory examination showed no obvious abnormalities. Abdominal contrast-enhanced CT found slight thickening of the gastric body wall. Ultrasonic gastroscopy revealed a round protuberant mass that originated from the muscularis mucosa on the great curvature of the gastric body, with a largest diameter of 16 mm. After full communication with the patient and exclusion of contraindications, the patient successfully underwent diagnostic endoscopic submucosal dissection (ESD) surgery. The postoperative pathological findings, immunohistochemical staining panel and molecular detection all improved that the mass was leiomyosarcoma. After 18 months of follow-up, the patient was in good condition, and there was no relapse on gastroscopy and abdominal enhanced CT. Conclusion Gastrointestinal leiomyosarcoma can be successfully resected by minimally invasive endoscopic treatment with high safety, good tolerance, and satisfactory clinical results. This shows that ESD is an effective method for the treatment of these diseases and has promising prospects for clinical application.

Tumor-to-Tumor Metastasis of Renal Cell Carcinoma to a Follicular Variant of Papillary Thyroid Carcinoma: A Case Report and Literature Review

Renal cell carcinoma (RCC) is the most common renal malignancy. It has a variable clinical course with metastasis to unusual sites occurring months to years after the initial diagnosis. However, metastasis can also be the first presentation of RCC. Although relatively uncommon, the thyroid gland is the most common location for RCC metastasis in the head and neck region. Tumor-to-tumor metastasis is an exceedingly rare occurrence. Only 10 cases were reported of RCC metastasis to primary thyroid neoplasms.We present a case of clear cell RCC metastasizing to a follicular of variant papillary thyroid carcinoma (FVPTC) 14 years after the initial diagnosis of RCC. A review of similar reported cases revealed that the most common primary thyroid recipient of tumor-to-tumor metastasis of RCC was FVPTC. The rich lymphovascular network in FVPTC compared to other thyroid tumors, which may promote the deposition of metastatic tumor cells, might explain this predilection.Careful review of the clinical and radiological findings and checking for any history of malignancy when examining thyroid nodules is important for guiding further studies. Performing a targeted panel of immunohistochemical stains for any suspicious areas is also essential for the diagnosis of such unusual cases.

Primary diffuse large B-cell lymphoma of the uterus – A case report

Extranodal non-Hodgkin’s lymphoma (NHL) constitutes one fifth to one third of all cases of NHL. Secondary lymphomatous involvement of the female genital tract (FGT) is not rare and is often seen in disseminated disease; however, primary NHL of the FGT is extremely rare. The uterine corpus is only third to the ovaries and uterine cervix as a site for primary NHL of the FGT. Differentiation between primary and secondary involvement of FGT organ by a haematolymphoid neoplasm relies upon the localisation versus dissemination of the disease at time of diagnosis. We report a case of a 71-years-old lady with primary diffuse large B-cell lymphoma (DLBCL) of the uterine corpus. The histology showed a diffuse infiltrate of large atypical discohesive cells associated with multinucleated tumour cells and brisk mitosis. A panel of immunohistochemical stains showed results consistent with the diagnosis of DLBCL made on routine stains. There was only one involved sentinel node, and radiologically there was no evidence of other involved sites by lymphoma. Designation of the lymphoma as primary to the FGT is clinical and having appropriate imaging studies of the patient is vital for this purpose.

EBV-positive Diffuse Large B-Cell Lymphoma, NOS in a Filipino Patient: Mimickers and Essential Ancillary Studies

Epstein-Barr virus positive diffuse large B-cell lymphoma (EBV+ DLBCL) is prevalent among Asians but is underreported in the Philippine setting. We report the case of an 88-year-old male who presented with difficulty swallowing. CT scan showed an ill-defined soft tissue focus with calcifications in the supraglottic to hypopharyngeal region measuring approximately 2.6 x 1.7 x 1.5 cm, and multiple lymphadenopathies in the head and neck. Biopsy of the masses at the left tonsil, left arytenoid mucosa, pyriform sinus, and aryepiglottic fold showed large lymphoid cells with several Reed-Sternberg-like cells in a background of small lymphocytes, neutrophils, few eosinophils and histiocytes. A panel of immunohistochemical stains and EBER-ish were performed to differentiate among six entities that were morphologically similar to the patient’s case, namely, classic Hodgkin lymphoma, T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL), DLBCL, NOS, anaplastic variant, B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and classic HL (gray zone lymphoma), and infectious mononucleosis (IM). The neoplastic cells expressed CD20, CD30, CD45, PAX5, CD10, MUM-1, BCL6, BCL2, and c-myc, while CD3, CD15 and ALK-1 were negative. The cells of interest also showed nuclear staining (30-40%) on Epstein-Barr virus encoding RNA in-situ hybridization (EBER-ish). The Ki-67 showed a proliferation index of 40-50%. Given the differences in prognosis and treatment among these diseases, judicious use of immunostains and EBER-ish is recommended for accurate diagnosis.