CD34 Positivity Research Articles

EWSR1::CREM rearranged intra-abdominal malignant epithelioid neoplasm: two new cases of an emerging entity with clinicopathological characteristics and histological pitfalls.

The EWSR1::CREM rearranged intra-abdominal malignant epithelioid neoplasm is an emerging tumor, with only a few publications describing it to date. Here, we report two new cases of this highly aggressive tumor, primarily involving the peritoneal surface. The tumors presented as a widespread diffuse peritoneal lesion associated with a 4-cm pelvic mass in a 28-year-old woman (Case 1) and as a 10-cm intra-abdominal mass infiltrating the stomach with multiple hepatic metastases in a 53-year-old woman (Case 2). The tumors shared predominant epithelioid morphology with minimal nuclear polymorphism. One of them additionally harbored spindle and rhabdoid cell populations. Both tumors displayed immunoreactivity for pan-cytokeratins, EMA, and CD99, and variable positivity for MUC4, progesterone and estrogen receptors, pan-NTRK, and synaptophysin. This misleading histology and immunophenotype give rise to a wide spectrum of differential diagnoses and highlight the crucial role of RNA sequencing in diagnostic accuracy and thus in appropriate therapeutic approaches.

Case report: Chemotherapy plus sintilimab for the treatment of gastroesophageal junction hepatoid adenocarcinoma with liver metastasis: a case study with literature review

ObjectiveTo elucidate the clinicopathological features and treatment of metastatic gastroesophageal junction hepatoid adenocarcinoma (GEJ HAC)using a case study and literature review.MethodsClinical presentation, results of histology and immunohistochemistry, and next-generation sequencing(NGS) in a patient with GEJ HAC metastasizing to the liver were reviewed. Chemotherapy (SOX or S-1) plus sintilimab was administered.ResultsA 65-year-old male patient with a history of hypertension was admitted to the hospital due to a one-week increase in serum AFP levels. There was a small intraluminal mass at the GEJ and a metastatic lesion in liver segment VIII, as well as enlarged perigastric and retroperitoneal lymph nodes. Tumor cells in both the GEJ and liver tissue exhibited a glandular shape with a nest-like adenoid structure. Immunohistochemical (IHC) analysis of the GEJ tissue showed positivity for AFP, CA19-9, CK7, CK20, MUC-1, P53 (wild type), Glypican-3, and HepPar-1, and negativity for Arginase-1, CD10, and Her-2. In the metastatic liver tissue, IHC testing demonstrated positivity for AFP, CD10, CK19, CK20, HepPar-1, MUC-1, Ki-67, and P53 (wild type), while CK7 was negative. The NGS report of GEJ mass indicated that the JAK2 and TP53 genes harbored missense mutations, while the MLH1, MSH2, MSH6, PMS2, ERBB2, EGFR, PIK3CA, APC, CTNNB1, CDH1, and DPYD genes were normal. The patient’s serum levels of CEA, CA19-9, and AFP were sharply decreased. The patient achieved a major pathological response (MPR) and remains in a progression-free stage.ConclusionsSintilimab-based chemotherapy has proven efficacy in achieving a MPR and maintaining a progression-free state for a patient with GEJ HAC that has metastasized to the liver.

Case report: Tongue metastasis as an initial sign of clear cell renal cell carcinoma and its prognosis

Clear cell renal cell carcinoma (ccRCC) is the most prevalent and lethal subtype of renal cell carcinoma (RCC), characterized by a poor prognosis and a high likelihood of distant metastasis. Nonetheless, metastasis of ccRCC to the tongue remains rare. Diagnosing and planning treatment for patients who initially present with tongue metastasis can be particularly challenging, as few cases have been reported in the literature. We present a case of a 62-year-old man who presented with a painful lump on the right anterior border of his tongue. Histological examination revealed lobulated and nested epithelial cell clusters with moderate dysplasia and frequent mitotic figures within the lamina propria. Immunohistochemistry showed positivity for vimentin, CD10, PAX-8, and epithelial membrane antigen (EMA), but negativity for PAX-2, calponin, S-100 protein, periodic acid-Schiff with diastase (PAS-D), P63, P40, and CK7, confirming the diagnosis of ccRCC metastasis to the tongue. After comprehensive evaluation and multidisciplinary team consultation, the patient underwent cytoreductive nephrectomy (CN), metastasectomy, and targeted therapy. According to the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1, the patient maintained stable disease (SD) during systemic treatment. Unfortunately, treatment was discontinued due to adverse drug reactions, and the patient was transitioned to palliative care. His disease progressed to progressive disease (PD), and he ultimately succumbed to systemic infection, with a progression-free survival (PFS) of approximately 15 months. This case highlights the urgent need for improved therapeutic strategies to manage symptoms and prolong survival in patients with this rare metastatic presentation.

Primary Hyperparathyroidism-Phosphaturic Mesenchymal Tumour: An Unusual Association and a Probable Syndrome

Phosphaturic Mesenchymal Tumour (PMT) is a rare and underdiagnosed tumour that causes Tumour-Induced Osteomalacia (TIO). These tumours produce Fibroblast Growth Factor-23 (FGF23), which inhibits renal tubular phosphate reabsorption, leading to hyperphosphaturia and oncogenic osteomalacia. The association of primary Hyperparathyroidism (pHPT) with PMT is extremely rare, with only two cases reported in the literature to date. A 51-year-old male presented in a bedridden state with multiple episodes of fractures throughout his skeleton over six years. Investigations revealed mild hypocalcaemia, marked hypophosphatemia, elevated serum Alkaline Phosphatase (ALP), low 25-Hydroxy Vitamin D, and persistently raised Parathormone (PTH) levels. A 68-Ga-DOTANOC 3D PET (Positron Emission Tomography) scan revealed a 4.1×3.2×2.5 cm DOTA avid mass in the right thigh. FGF23 levels were found to be 1466 pg/mL. A diagnosis of hypophosphatemic osteomalacia with pHPT was made, and the mass was subsequently excised. The thigh mass measured 3.5×2.5 cm and had a tan-brown cut surface. Microscopy revealed a benign spindle cell tumour with a vasoformative pattern and areas of grungy calcification. Immunohistochemistry demonstrated strong positivity for Vimentin, while CD34, CD68, CK, and Desmin were negative. A diagnosis of PMT, Mixed Connective Tissue type, was established. Normal phosphate, calcium, and FGF23 levels were restored after surgery, and the patient was able to walk again. This unusual case of a patient with pHPT and PMT, and the possible existence of a “pHPT-PMT syndrome, “was reported in the Times of India on November 20, 2022, as “Rare phosphorus-guzzling tumour left Dongri man bedridden for three years.” The exact aetiology for the association of PMT and pHPT is not known, and the hypothesis of aberrant gene expression has been implicated.

Expanding the Range of Epithelial Marker and SMA Staining of Superficial CD34+ Fibroblastic Tumors: A Case Report and Review of the Literature.

Superficial CD34+ fibroblastic tumor (SCD34FT) is a relatively recently described borderline mesenchymal neoplasm. Owing to a relative lack of specificity in clinical presentation, radiopathologic findings, and immunohistochemical staining, the diagnoses of SCD34FT can be challenging. In this study, we present a case of a 55-year-old woman with an indolent painless nodule on the right shin. Histopathologic evaluation of the resected specimen showed a moderately cellular, subcutaneous lesion composed of spindled cells with mild pleomorphism arranged in sheets and fascicles. Immunohistochemical staining demonstrated diffuse positivity for CD34. Surprisingly, the tumor also showed diffuse expression of smooth muscle actin (SMA) and more than focal (ranging from subset to diffuse) expression of AE1/AE3 and CAM5.2. DNA and RNA next-generation sequencing revealed a t(X; 11)(q13; q24) MED12::PRDM10 fusion, confirming the diagnosis of SCD34FT. To the best of our knowledge, this is the first reported case highlighting SCD34FT with more extensive immunoreactivity to epithelial markers (AE1/AE3 and CAM5.2) and SMA compared with the focal staining reported in the existing literature. We hope that adding this case to the existing literature will raise awareness among pathologists to recognize the more variable staining pattern of epithelial markers and SMA when considering the diagnosis of SCD34FT.

CD23 expression in lymphoplasmacytic lymphoma: Clinical-pathological and biological correlations.

The diagnosis of lymphoplasmacytic lymphoma (LPL) in the bone marrow (BM) is challenged by aberrant phenotypes and by overlapping histological features with marginal zone lymphoma (MZL). To address these issues, we (i) assessed LPL immunophenotype on a large series of BM samples, (ii) drew possible correlations between LPL phenotype and clinical/molecular data and (iii) investigated the role of new phenotypical markers in the differential diagnosis between LPL and MZL. The study retrospectively considered 81 clinically annotated LPL diagnosed at Padua University Hospital (Padua, Italy) during a 5-year period. BM findings were correlated with clinical laboratory findings and with MYD88 and CXCR4 mutational status. The obtained results were compared with a series of 77 MZL in the BM, including 46 splenic MZL (SMZL), 14 nodal MZL (NMZL) and 17 extra-nodal MZL (EMZL). The LPL cohort included 52 males and 29 females (median age at diagnosis=71 years). Aberrant CD10 and CD5 positivity was documented in 3 of 81 (3.7%) and 13 of 81 (16.1%) cases, respectively. CD23 positivity occurred in 56 of 81 (69.1%) cases, being usually partial/focal. CD23 expression did not correlate with any specific clinical-pathological parameter. Comparison with SMZL, NMZL and EMZL highlighted less frequent splenomegaly, higher serum paraprotein, higher CD23 expression and fewer follicular dendritic cell networks in LPL. A combined clinical-pathological score supported the differential diagnosis between LPL and MZL of any type. The highest diagnostic yield was obtained for the differential diagnosis between LPL and SMZL. Partial positivity for CD23 is a common feature of LPL in the BM. Together with other clinical and histological parameters, CD23 expression supports the differential diagnosis between LPL and MZL.

Oral Kaposi sarcoma in Brazil: a case series of 40 patients highlighting a significant health burden.

The aim of this study was to provide a comprehensive clinicopathological analysis of oral Kaposi sarcoma (KS) cases and examine its relationship with HIV-related immunosuppression. Paraffin-embedded tissue blocks of patients microscopically diagnosed with oral KS were retrieved from three oral and maxillofacial pathology files. Data including clinical, laboratory, microscopic and immunohistochemical findings and treatment employed were retrieved. A total of 40 patients with an average age of 33.5 years, with a male predominance were retrieved. The most common site was the hard palate, followed by the gingiva. Oral lesions were the first sign of KS in 57.5% of cases. Laboratory findings revealed an average viral load of 185,416 copies/mL, a mean CD4 count of 159.95 cells/mm³, CD8 count of 1062.65 cells/mm³, and a CD4/CD8 ratio of 0.148 cells/mm³. Histopathology showed spindle-shaped cell proliferation, vascular channels, hemorrhage, and hemosiderin deposits. Immunohistochemistry confirmed positivity for CD34, CD31, and HHV-8. Patients were treated with highly active antiretroviral therapy (HAART) (75%), and chemotherapy (47.5%). Oral KS remains a significant marker of HIV-related immunosuppression, especially where the burden of disease remains substantial. While HAART plays a critical role in managing KS, combined chemotherapy is often necessary for advanced cases.

TMIC-45. CYTOMEGALOVIRUS PP65 ANTIGEN EXPRESSION FOLLOWING PP65-SPECIFIC DENDRITIC CELL VACCINATION IN MATCHED PRIMARY AND RECURRENT GLIOBLASTOMA SPECIMENS

Abstract BACKGROUND Human cytomegalovirus (HCMV) expression in glioblastoma (GBM) has been corroborated by multiple independent laboratories. HCMV genes have been directly linked to GBM cell proliferation, invasion, and angiogenesis. The HCMV tegument protein pp65 has served as a tumor-specific antigen in serial pp65 RNA-pulsed autologous dendritic cell (DC) vaccine trials. Here we report pp65 expression in matched primary and recurrent GBM samples from those trials following pp65-DC vaccination. METHODS Paired GBM specimens were collected from patients receiving pp65-DC vaccines according to ATTAC and ATTAC-GM clinical trials (NCT00639639). Of 23 treated patients, 9 cases were available for analysis. Formalin-fixed paraffin-embedded specimens were mounted on glass slides and stained for pp65 via immunohistochemistry (IHC). CD31 served as a control for tissue quality and to investigate the role of pp65 co-staining in the tumor perivascular niche. RESULTS Of 9 available cases, 5 were excluded due to poor tissue quality/absent CD31 staining on aged slides. Among the remaining four cases, three showed pp65 staining in non-vascular and perivascular areas within both primary and recurrent samples. However, recurrent specimens of these positive cases demonstrated a clear reduction in both intensity and distribution of pp65 staining within non-vascular regions but retained a strong positivity within the perivascular space. The fourth case showed absent pp65 staining and only weakly positive CD31 staining in both primary and recurrent specimens. Necrotic areas within pp65-positive slides showed minimal to no pp65 staining. CONCLUSIONS This study confirms HCMV pp65 expression in both primary and recurrent GBM following pp65-DC vaccination, with an interesting phenomenon of retained pp65 expression specifically in the perivascular niche. These findings support the role of HCMV in GBM angiogenesis and tumor progression as well as mechanisms of immune evasion following single antigen vaccine platforms. Our study reinforces the importance of tissue quality for proper HCMV detection in GBM.

Microvenular hemangioma located in the breast: a case report

Abstract Microvenular hemangioma (MVH) is a rare, benign type of hemangioma that typically presents as a solitary, slow-growing, red-to-violaceous asymptomatic papule, plaque, or nodule. It most commonly locations of the lesions on the limbs and trunk, with no prior reports of MVH confined to the breast. We present the first reported case of multiple MVH confined to the breast in a 17-year-old female patient. The case is notable for its unique and atypical clinical features. Diagnosing MVH is challenging and requires routine pathological and immunohistochemical staining. Histological testing revealed typical features of MVH, irregularly branched small or medium vascular interstitial spaces lined with benign endothelial cells and positivity for CD34 and CD31. This case emphasizes the need to consider MVH in the differential diagnosis of breast vascular lesions, particularly in young patients. It also underscores the importance of histological and immunohistochemical analyses for an accurate diagnosis.

Reevaluating hybrid neurofibroma/schwannoma: Predominance of schwannoma features despite CD34 positivity and initial neurofibroma diagnosis.

Schwannomas consist of both high-cellularity regions (Antoni A area) and hypocellular regions (Antoni B area) in histopathological findings. Neurofibromas characteristically consist of CD34 positive spindle cells with thin, wavy, nuclei and wavy collagen bands. Previous reports have described segments of schwannomas with neurofibroma features as hybrid tumors, although hybrid tumors were diagnosed based on partial CD34 positivity in many previous reports. On the other hand, the Antoni B area of some schwannomas was reported to be positive for CD34. Therefore, the definition of a hybrid tumor has not been clear. The objective of this study was to determine whether only CD34 positive findings in schwannomas could be used to define a hybrid tumor. In the analysis of our patient with schwannomatosis caused by a novel LZTR1 germline mutation, part of the tumor had CD34 positive hypocellular regions. These regions contained no thin, wavy, nuclei, indicating an Antoni B area. Laser microdissection was used to investigate the genetic background and differences in molecular mechanisms between CD34 positive and CD34 negative regions. All mutations identified in CD34 positive regions were also found in CD34 negative regions. Our data could not clear the genetic background of Antoni B which was CD34 positive area. We then reviewed the pathologies of 66 sporadic schwannomas. Histopathological examinations of all schwannomas revealed the absence of thin, wavy, nuclei and wavy collagen bands, and no hybrid tumors were found in any of the cases. Ten of 66 patients were randomly selected for CD34 immunostaining and positivity was found in all cases. Our data suggest that it is difficult to distinguish schwannomas by staining for CD34 alone, as Antoni B areas can also be positive for CD34. Therefore, CD34 staining alone should not be used to diagnose hybrid tumors in patients with schwannomas.

Soft-tissue keratocyst: report of 3 new cases from Brazil.

To describe the clinicopathological features of 3 new cases of soft-tissue keratocyst (STK) of the buccal mucosa from Brazil. Clinical data from 3 patients diagnosed with STK were obtained from the archives of the Laboratory of Oral Pathology at the Federal University of Rio de Janeiro- Brazil from 2020 to 2023. Two oral pathologists reviewed conventional hematoxylin and eosin-stained slides of each case. Immunohistochemical stainings for CK19, Bcl-2, CD138, D2-40, EMA, and Ki-67 were performed in all cases. Case 1 was a 58-year-old man with a 2-year history of painless swelling of the right buccal mucosa, measuring approximately 5cm. Case 2 was of a 44-year-old man with a painful swelling in the left buccal mucosa lasting 3 years with drainage to the oral cavity. Case 3 was of a 74-year-old woman with a painful swelling in the left buccal mucosa of unknown duration. Microscopic evaluation of all 3 cases revealed a cyst lined with a few cell layers composed of columnar palisading basal cells and a corrugated parakeratin surface. The capsule comprised fibrous connective tissue with variable amounts of blood vessels with hemorrhage, nerve bundles, fat tissue, striated muscle fibers, and the absence of pilosebaceous units. No recurrence was observed after complete surgical removal. All epithelial layers of the 3 cases expressed positivity for CK19 and CD138, the basal cells were positive for Bcl-2 and D2-40, and the superficial epithelial layer was positive for EMA. All cases demonstrated a low proliferation index by Ki-67. This study represents a series of 3 cases of STK that affected the posterior buccal mucosa of middle-aged patients from Brazil, sharing histopathological and immunohistochemical features with odontogenic keratocyst.

Auricular epithelioid hemangioendothelioma: Two cases first diagnosed as auricular pseudocyst.

Epithelioid hemangioendothelioma (EHE) is a rare soft-tissue vascular neoplasm with a prevalence of one in one million. The present study firstly reports two cases of EHE occurring in the auricle. The clinical, histopathological and immunohistochemical features of two patients with auricular EHE are described, and the associated literature are reviewed. Two adult male patients each presented with an asymptomatic, unilateral soft skin-colored noninflammatory swelling of the auricle. Based on their clinical manifestations, both patients were initially diagnosed with auricular pseudocysts. Auricular excision surgery was performed under general anesthesia. The resected specimens were sent for pathological examination. Immunohistochemical examination showed that the specimens were positive for CD31, CD34, friend leukemia integration 1 (FLI-1), coagulation factor 8 and E26 transformation-specific-related gene, which was consistent with EHE. Follow-up after surgery showed no evidence of tumor recurrence. It may be concluded EHEs of low malignancy should be included in the differential diagnosis of patients with auricular pseudocysts. EHEs can be diagnosed based on their morphological and histological characteristics, with immunohistochemical positivity for FLI-1 and CD31 being suggestive of a diagnosis of EHE.

DICER1 Syndrome in a 25-Year-Old Female: Autopsy Case Report of Mixed Sex Cord-Stromal and Primitive Sarcoma Tumors with Diverse Differentiation Patterns

Abstract Introduction/Objective DICER-1 syndrome is a rare disorder characterized by germline mutations in the DICER1 gene, known to confer a lifetime risk of developing a variety of benign and malignant pathologies. This syndrome typically affects young individuals, though it exhibits exceedingly variable and relatively low penetrance of the neoplastic manifestations. Methods/Case Report We report on a 25-year-old woman with a history of metastatic DICER-1 related mixed pattern sex-cord stromal tumor of the ovary and primitive sarcoma of the liver. Her treatment involved extensive surgeries, including oophorectomy, salpingectomy, and partial hepatectomy, and multiple cycles of chemotherapy. Antemortem surgical pathological analyses revealed a poorly differentiated, primitive sarcoma in the liver and a sex cord-stromal tumor with Sertoli-Leydig and juvenile granulosa cell tumor-like features. The liver tumor exhibited a primitive spindle cell sarcoma with anaplastic features as well as chondrosarcomatous and rhabdomyosarcomatous patterns, suggesting a primary DICER1-related sarcoma. Immunohistochemistry confirmed the tumor’s complex multilineage differentiation, showing variable positivity for CD99, vimentin, CD10, BCL2, and Glypican-3. Positivity for Desmin and MyoD1 was focal, while the tumor was negative for inhibin, calretinin, AE1/3, AFP, and beta-catenin, overall supporting a DICER1-associated sarcoma diagnosis. She eventually died from terminal cardiac arrest secondary to complications from her metastatic cancer. An autopsy revealed a significant abdominopelvic mass leading to hemoperitoneum and extensive organ involvement, highlighting the aggressive nature of DICER1-associated malignancies. Results (if a Case Study enter NA) NA Conclusion This case underscores the importance of recognizing the broad manifestations of DICER-1 syndrome for accurate diagnosis, genetic counseling, and tailored management. Highlighting tumor morphology and immunohistochemical features enriches our understanding of DICER-1 pathology, advancing diagnosis and treatment prospects for affected individuals.

A Diagnostic Challenge in the Biopsy of a Mammographic Abnormality

Abstract Introduction/Objective Primary breast marginal zone lymphoma (MZL) is an uncommon subtype of extranodal lymphoma, and its diagnosis presents challenges, particularly in distinguishing it from lymphoplasmacytic lymphoma (LPL). MYD88 L265P mutation has been identified in a subset of marginal zone lymphomas, comprising 6-9% of cases. This genetic alteration further complicates the differentiation between MZL and LPL in breast tumors. We present a case highlighting the diagnostic complexities associated with primary breast MZL. Methods/Case Report A 71-year-old female patient underwent mammographic screening, which revealed a suspicious lesion in her left breast. Subsequent PET scan showed a hypermetabolic area consistent with a primary breast lesion. Biopsy histology exhibited a diffuse atypical lymphoid infiltration with varying proportions of neoplastic lymphocytes. Immunohistochemical analysis revealed positivity for CD20, PAX5, BCL2, CD138, MUM1, and negativity for CD3, CD5, Cyclin D1, CD10, CD23, CD34, BCL6, TDT, CD30, GATA3, and CK AE1/3. Additionally, there was lambda light chain restriction, and the Ki67 proliferation rate index was approximately 50%. Fish analysis indicated abnormal BCL6 gene rearrangement. Molecular genetic testing confirmed the presence of MYD88 mutation with c.794T>C p.L265P. Notably, bone marrow biopsy showed no abnormalities, with normal hematopoiesis. Serum electrophoresis and immunofixation detected an IgM monoclonal protein with lambda light chain specificity. Results (if a Case Study enter NA) NA Conclusion The diagnosis of primary breast MZL was favored over LPL due to the absence of common LPL- associated symptoms such as bone marrow involvement. However, the distinction between these entities remains challenging, underscoring the importance of comprehensive diagnostic approaches integrating histopathology, immunohistochemistry, and molecular genetics. Further research is warranted to enhance diagnostic certainty in such cases, particularly as the management of MZL and LPL becomes increasingly specific with the advent of novel therapeutic agents and ongoing clinical trials.

Isolated Perianal Langerhans Cell Histiocytosis in a Human Immunodeficiency Virus-Positive Adult: A Rare Incidental finding

Abstract Introduction/Objective Langerhans cell histiocytosis (LCH) is a rare disorder characterized by abnormal proliferation of antigen-presenting cells, primarily Langerhans cells. Although it commonly affects bones, skin, and lungs, involvement of the gastrointestinal tract is rare. Specifically, isolated perianal LCH is exceptionally uncommon, with only a few documented cases reported in the literature. Here, we report a case of incidental perianal LCH in an adult HIV patient, highlighting the exceptional rarity and clinical importance of this occurrence. Methods/Case Report A 56-year-old Caucasian male with HIV underwent surgical resection of a 0.5 x 0.4 x 0.3 cm verrucous lesion on the posterior anal margin. His past medical history included granulomatous lymphadenitis, penile warts, and anal dysplasia. Microscopic examination of the excised tissue revealed Langerhans cells with characteristic features, including abundant eosinophilic cytoplasm and irregular nuclear membranes (resembling “coffee-bean” or “folded paper” appearance). Immunohistochemical analysis confirmed the diagnosis by demonstrating positivity for CD1a, S100, and CD68. The BRAF mutation was evaluated on the same paraffin-embedded block, which revealed the lack of the mutant BRAF V600E. PET-CT imaging showed no evidence of metastatic disease, emphasizing the isolated nature of the perianal LCH in this patient. Results (if a Case Study enter NA) NA Conclusion This case highlights the significance of recognizing and thoroughly evaluating rare and incidental conditions such as LCH in HIV patients. Our findings emphasize the importance of maintaining a high index of suspicion for LCH among healthcare providers and ensuring proper follow-up to rule out systemic involvement. Furthermore, there is a need for future studies to investigate the correlation between LCH and HIV. Given its rarity and diverse clinical presentation in immunocompromised individuals, a multidisciplinary approach, tailored treatment plans, and long-term surveillance with imaging modalities like PET/CT are essential for effectively managing adult-onset isolated LCH.

Intravascular Nodular Fasciitis Mimicking Thrombotic Complications in a 16-year-old male with May-Thurner Syndrome

Abstract Introduction/Objective Nodular fasciitis is a rare benign myofibroblastic proliferation commonly mistaken for malignant tumors due to its rapid growth and clinical presentation. May-Thurner Syndrome (MTS), characterized by compression of the left common iliac vein by the right common iliac artery, predisposes individuals to deep vein thrombosis (DVT). However, here we present a unique case of intravascular nodular fasciitis presenting as thrombotic complications in the context of MTS in a 16-year-old male. Methods/Case Report A 16-year-old male presented with progressive left hip and leg pain accompanied by recent swelling. Ultrasound revealed occlusive thrombi within the left side external iliac, common superficial femoral, and great saphenous veins, along with nonocclusive thrombi in left deep femoral vein. Magnetic resonance venography confirmed MTS and extensive thrombosis. Thrombectomy was done with fragments sent to pathology. Microscopic examination showed cellular areas with loose myxoid composition, proliferating spindle, myofibroblastic/fibroblastic, and stellate cells arranged in irregular bundles. Additional microscopic findings included mild cellular atypia, mitoses, focal macrophage aggregates, occasional multinucleate forms, foci of hemorrhage, fibrin exudate, ingrowing fibroblasts, and increased vascularization. Immunohistochemical stains demonstrated positivity for SMA, CD31, ERG, and CD34, highlighting prominent vascularization, while desmin, myogenin, myoglobin, STAT6, beta-catenin, S100, and AE1/AE3 were negative. Differential diagnosis included intravascular fasciitis, and possibly organizing thrombus with myxoid stroma. USP6 gene rearrangement (FISH) study was positive, confirming the diagnosis of nodular fasciitis. Results (if a Case Study enter NA) N/A Conclusion This case emphasizes the significance of maintaining a broad differential diagnosis when assessing specimens sent as thrombectomies. Recognizing intravascular nodular fasciitis as a potential presentation mimicking thrombosis is essential for accurate diagnosis and management.

Solid-basaloid Variant of Mammary Adenoid Cystic Carcinoma – Report of an Unusual Case with Literature Review

Abstract Introduction/Objective Adenoid cystic carcinoma (AdCC) of breast is a rare subtype of malignancy, constituting approximately 0.1% of all breast carcinomas. The solid-basaloid variant (SB-AdCC) is exceedingly uncommon. Here, we present such an unusual case of SB-AdCC. Methods/Case Report A 64-year-old woman who underwent screening mammography presented with abnormal findings, revealing a hypoechoic ovoid, lobulated nodule at 7:00 of the left breast, which prompted an ultrasound- guided biopsy. Histologically, the biopsy cores demonstrated a 9 mm infiltrative round, solid nests with focal “cribriforming” areas. It was composed of monomorphic basaloid epithelial cells with marked nuclear atypia and high mitotic count. High-grade ductal carcinoma in situ, solid papillary carcinoma, and nonspecific invasive carcinoma were in differentials. Immunohistochemical (IHC) staining expressed positivity for CD117 and CK 5/6, while p63, SMMHC, and synaptophysin were negative. MYB gene rearrangement confirmed by fluorescence in situ hybridization. As expected, the tumor lacked ER, PR, and HER2 expression by IHC. Left breast mastectomy and axillary lymph node dissection have been scheduled. Results (if a Case Study enter NA) NA Conclusion Per literature review, the mean age of SB-AdCC at diagnosis was 68 years (33-84 years) with an average tumor size of 25 mm (12-70 mm). It had more aggressive behavior, with a higher propensity for lymph node metastasis, locally recurrence, and distant metastasis. The median disease-free survival was 46.5 months versus 151.8 months in those with class AdCC. Notably, neovascularization has emerged as a strong independent predictor of outcome in SB-AdCC. Most patients were treated with surgical excision, axillary lymph node dissection, and/or adjuvant chemotherapy. Limited studies demonstrated that neoadjuvant chemotherapy may induce an excellent response. Furthermore, a distinct molecular mutation enriched in NOTCH and CREBBP genes has been identified, which could be novel potential therapeutic target. Thus, awareness of this extremely rare breast cancer subtype and accurate differentiation from other entities are paramount for appropriate management strategies.

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.

Rare Presentation of Extraskeletal Osteosarcoma Mimicking Phyllodes Tumor

Abstract Introduction/Objective A 57-year-old female presented with a palpable mass in the left breast, measuring up to 9 cm by ultrasound. core needle biopsy identified an atypical spindle cell lesion. The differential diagnosis included a metaplastic carcinoma, borderline phyllodes tumor, malignant phyllodes tumor with potential sarcomatous transformation. Methods/Case Report Histological examination of the tumor was performed, and immunohistochemical stains were conducted to characterize the lesion. Further consultation with a specialized pathologist at the University of Michigan was sought to confirm the diagnosis. Molecular analysis was performed to assess for specific genetic alterations and expression patterns. The histological examination revealed a proliferation of atypical spindle cells forming a fascicular and storiform pattern, with numerous large, pleomorphic, multinucleated tumor cells and a high mitotic rate. Immunohistochemical stains showed strong positivity for CD10 and vimentin, with focal weak expression for desmin, and negativity for a broad panel of cytokeratins and other markers. Consultation with Dr. Abbott at the University of Michigan supported the diagnosis of extraskeletal osteosarcoma. Molecular analysis revealed PD-L1 expression and absence of NTRK gene fusions. FISH analysis showed suggestive alterations including loss of BRAF gene, loss of MYC, and suggestive gains or polysomy of PTEN gene. Results (if a Case Study enter NA) NA Conclusion The case represents a rare presentation of extraskeletal osteosarcoma in the breast, with distinctive histological and immunohistochemical features. The comprehensive workup including histology, immunohistochemistry, and molecular analysis aids in accurate diagnosis and potential therapeutic implications. Further research may elucidate the underlying mechanisms and treatment options for this uncommon malignancy.

Malakoplakia, a rare inflammatory condition presenting as a colon polyp

Abstract Introduction/Objective Malakoplakia is a rare histiocytic disease caused by defects in phagocytic or degradative functions of histiocytes in response to gram negative coliforms (E. coli or Proteus) that results in chronic inflammatory state, followed by intracellular deposition of iron and calcium (known as Michaelis-Gutmann bodies). It’s more common in immunocompromised patients and the mean age at diagnosis is fifth decade. It occurs in all organs, common in GU tract, particularly bladder, but also seen in gastrointestinal tract (most commonly colon, followed by stomach and duodenum), central nervous system and female genital tract. In gastrointestinal tract, it can present as a polyp with diffuse mucosal involvement, submucosal thickening, and even may cause mass. Methods/Case Report A 60 -year-old male smoker presented to our hospital with history of colon polyps; colonoscopy revealed a 6 mm sessile polyp at the hepatic flexure. A biopsy was performed which showed numerous epithelioid histiocytes with granular eosinophilic cytoplasm, abundant Michaelis-Gutmann bodies and increased lymphocytes. Immunohistochemical stains showed diffuse positivity for CD68; and PAS stain was positive for histiocytic cytoplasmic granules. Based on this data, the diagnosis of Malakoplakia was confirmed. Malakoplakia is treated with antibiotics that concentrate in macrophages (quinolones or trimethoprim-sulfamethoxazole), antibiotics directed against E. coli, surgery and possibly discontinuation of immunosuppressive drug therapy. Results (if a Case Study enter NA) Malakoplakia, in this case, was presented clinically as a sessile colon polyp and histologically showed numerous epithelioid histiocytes with granular eosinophilic cytoplasm, with Immunohistochemical stains (CD68; and PAS stain) the correct diagnosis was made. Other presentations of Malakoplakia include diffuse mucosal involvement, submucosal thickening, or mass. Histologically, it may rarely be mistaken as signet ring carcinoma. These variable presentations in GU tract or colon can be interpreted as malignancy with consequent unnecessary interventions. Hence, awareness of Malakoplakia with careful histopathologic examination and the use of immunohistochemical studies are advisable in that cases. Conclusion We would like to emphasize that Malakoplakia can be clinically and histologically misdiagnosed as a malignant condition; therefore histopathologic and immunohistochemical studies are needed to correctly diagnose this entity.