Positivity For Synaptophysin Research Articles

Benign Glomus Tumor of the Urinary Bladder: A Case Report and Literature Review.

Glomus tumor is a rare neoplasm, typically found in superficial soft tissues and extremities, particularly in the subungual region. However, it can also occasionally affect deep soft tissue or viscera, such as the bladder, albeit infrequently. Our patient was a 51-year-old man presenting with recurrent hematuria of unknown etiology, accompanied by a blood clot that resolved spontaneously after 1 day. Abdominal computed tomography revealed multiple calculi in the right kidney, whereas cystoscopy showed mucosal edema on the left side of the bladder. A magnetic resonance image of the bladder identified an ovoid mass on the left side, measuring approximately 3.1 cm × 2.7 cm × 2.1 cm. This mass demonstrated a slightly increased signal intensity on T2-weighted images and an intermediate signal intensity on T1-weighted images. These findings suggested a malignant tumor in the urinary bladder with a nonfunctional right kidney. The patient underwent laparoscopic surgery to remove the right kidney and part of the bladder. Histologically, the tumor primarily consisted of round cells and abundant eosinophilic or pale cytoplasm. Immunohistochemical staining demonstrated diffuse positivity for smooth muscle actin and vimentin, and focal positivity for synaptophysin. The final pathological diagnosis was a bladder glomus tumor. At 15 months after resection, the patient was in good health with no recurrence or metastasis. The clinical manifestations and imaging features of bladder glomus tumors can pose diagnostic challenges for urologists. Therefore, it is imperative to consider this tumor in the differential diagnosis of bladder tumors and to enhance the understanding among urologists and pathologists regarding this entity.

The Clinical and Molecular Landscape of Rosette-Forming Glioneuronal Tumors.

Rosette-Forming Glioneuronal Tumors (RGNTs) are rare, typically benign central nervous system tumors primarily located in the fourth ventricle and pineal region. Despite being classified as WHO grade I with generally favorable prognoses, RGNTs present complexities in their molecular mechanisms, occasional malignant transformation, and epidemiological characteristics that require further investigation. This study systematically reviews the existing literature to analyze the epidemiological patterns, MRI characteristics, pathological features, diagnostic challenges, and molecular mechanisms associated with RGNTs, aiming to provide a comprehensive theoretical foundation for clinical practice and future research. Through an in-depth review of recent studies, key molecular mechanisms, including mutations in FGFR1, PIK3CA, TERT, and IDH1/2, are highlighted. Additionally, the challenges in accurate diagnosis and the potential for misdiagnosis are discussed, emphasizing the importance of thorough molecular analysis in clinical settings. The literature indicates that RGNTs predominantly affect young adults and adolescents, with a slight female predominance. MRI typically reveals mixed cystic-solid lesions, often accompanied by hydrocephalus. Pathologically, RGNTs are characterized by a combination of neuronal and glial components, with immunohistochemical staining showing positivity for Synaptophysin and GFAP. High frequencies of FGFR1 and PIK3CA mutations underscore the significance of these pathways in RGNT pathogenesis and progression. Although RGNTs generally exhibit low malignancy, the TERT mutations identified in some cases suggest a risk of malignant transformation. This study concludes that while current treatment strategies focus on surgical resection, integrating molecular diagnostics and targeted therapies may be essential for managing recurrent or refractory RGNTs. Future research should explore the impact of various gene mutations on tumor behavior and their correlation with clinical outcomes, to optimize individualized therapeutic strategies and improve patient survival and quality of life.

12325 Adrenocortical Carcinoma Masquerading As Pheochromocytoma In A Patient With Congenital Adrenal Hyperplasia

Abstract Disclosure: E.M. Niedzialkowska: None. A.A. Banka: None. Introduction: The development of adrenocortical carcinoma (ACC) in patients with congenital adrenal hyperplasia (CAH) is rare. The patients with CAH are at increased risk of adrenal tumors which is attributed to ACTH stimulation of adrenal gland if the disease is not appropriately treated. ACC cases mistaken for pheochromocytomas have been reported in the literature and are attributed to the variety of immunohistochemical markers expressed by the tumors. Case description:59 y.o female with salt-wasting CAH diagnosed at the age of 2 (21-hydroxylase deficiency) on hydrocortisone supplementation reported to the hospital due to episodes of sweating, tachycardia and hypertension. Work up revealed mildly elevated plasma normetanephrine 1 nmol/l (N <0.9), urine normetanephrine 1762 mcg (N<899), VMA 11.2 mcg/24hr (N 3.3-7.2). MRI of the abdomen revealed 2 left adrenal masses of 3.7 and 2.4 cm, right adrenal gland hyperplasia and low T1 and T2 enhancement. I-123 MIBG revealed increased activity and thickness of the right adrenal gland and no significant uptake on the left with nodular masses. The patient underwent left adrenalectomy with pathological report consistent with pheochromocytoma due to positive chromogranin and synaptophysin staining and moderate Ki activity. A year later follow up imaging showed an enhancing mass up to 7 cm at the suprarenal fossa invading the left kidney that was positive for nodular adrenocortical hyperplasia per pathology report. The patient continued to have elevated 17-OH- progesterone (2740 ng/l, N <51) despite compliance with her steroid therapy and suppressed ACTH. She underwent mass resection along with nephrectomy, splenectomy, partial colectomy and partial pancreatectomy. Pathology report was positive for adrenocortical carcinoma (positive chromogranin, synaptophysin, CAM 5.2, polycystic cytokeratin, Ki positive in greater than 10% of the tumor cells) with renal and regional lymph node invasion and colonic metastases. The patient was started on mitotane therapy but a year later PET scan was positive for liver and omental metastases and was subsequently started on carboplatin/etoposide followed by streptozocin/adriamycin with initial good response, however repeat PET a year afterwards showed progression of the liver lesions, metastases to omentum and metastatic lesion to calvarium and the patient expired soon afterwards. Discussion: CAH predisposes patients to adrenal tumors which is attributed to increased ACTH stimulation of the adrenal gland but ACC in this population is extremely rare. In very rare cases ACC can present clinically as pheochromocytoma with elevated catecholamine levels and positive synaptophysin and chromogranin staining which poses a clinical challenge. Both CAH and ACC can lead to increased androgen levels and ACTH levels can help to differentiate the origin of the hyperandrogenemia. Presentation: 6/2/2024

Aberrant positivity for BCOR immunohistochemistry in merkel cell carcinoma - a potential diagnostic pitfall

BackrgoundMerkel cell carcinoma (MCC) is a rare, aggressive primary cutaneous neuroendocrine carcinoma, frequently associated with clonal Merkel cell polyomavirus integration. MCC can pose significant diagnostic challenges due to its diverse clinical presentation and its broad histological differential diagnosis. Histologically, MCC presents as a small-round-blue cell neoplasm, where the differential diagnosis includes basal cell carcinoma, melanoma, hematologic malignancies, round cell sarcoma and metastatic small cell carcinoma of any site. We here report strong aberrant immunoreactivity for BCOR in MCC, a marker commonly used to identify round cell sarcomas and other neoplasms with BCOR alterations.MethodsBased on strong BCOR expression in three index cases of MCC, clinically mistaken as sarcoma, a retrospective analysis of three patient cohorts, comprising 31 MCC, 19 small cell lung carcinoma (SCLC) and 5 cases of neoplasms with molecularly confirmed BCOR alteration was conducted. Immunohistochemical staining intensity and localization for BCOR was semi-quantitatively analyzed.ResultsThree cases, clinically and radiologically mimicking a sarcoma were analyzed in our soft tissue and bone pathology service. Histologically, the cases showed sheets of a small round blue cell neoplasm. A broad panel of immunohistochemistry was used for lineage classification. Positivity for synaptophysin, CK20 and Merkel cell polyoma virus large T-antigen lead to the diagnosis of a MCC. Interestingly, all cases showed strong positive nuclear staining for BCOR, which was included for the initial work-up with the clinical differential of a round cell sarcoma. We analyzed a larger retrospective MCC cohort and found aberrant weak to strong BCOR positivity (nuclear and/or cytoplasmic) in up to 90% of the cases. As a positive control, we compared the expression to a small group of BCOR-altered neoplasms. Furthermore, we investigated a cohort of SCLC as another neuroendocrine neoplasm and found in all cases a diffuse moderate to strong BCOR positivity.ConclusionsThis study demonstrates that neuroendocrine neoplasms, such as MCC and SCLC can express strong aberrant BCOR. This might represent a diagnostic challenge or pitfall, in particular when MCC is clinically mistaken as a soft tissue or a bone sarcoma.

Ewing Sarcoma of Kidney: A Rare Entity

AbstractPrimary renal origin of Ewing sarcoma/PNET (primitive neuroectodermal tumor) is a rare entity in the adult population and has an aggressive outcome. The entity was first coined by Arthur Purdy stout in 1918 and recognized under family of small round cell tumor. Radiologically it is difficult to distinguish from primary clear cell carcinoma of kidney from Ewing/PNET. Diagnosis of this requires histopathology, immunohistochemistry (IHC), and cytogenetics studies.A 40-year-old female presented with hematuria and radiology found a mass lower pole of left kidney with extension into renal hilum. Nephrectomy was done for the case and the histopathology diagnosis of small round cell tumor of left kidney was given. Followed by IHC, diagnosis of malignant round cell tumor was suggestive of Ewing sarcoma.Microscopy showed cells with small, round, hyperchromatic nuclei, scant cytoplasm, and inconspicuous nucleoli. Increased mitosis was noted (15/10 high power field). Multiple foci of pseudorosettes, areas of hemorrhage, and necrosis lymphovascular emboli were seen.IHC done outside showed NKX 2-2, synaptophysin positivity, CD99 diffuse membranous positivity, cytokeratin perinuclear dot like positivity, and negative for CD20, CD3, desmin, CD34, S100, and Pax8. Impression of malignant round cell tumor was suggestive of Ewing sarcoma.Ewing sarcoma is one of the rare yet highly aggressive tumors. This should be kept as differential diagnosis in young adults with renal mass, as on radiologically it cannot be differentiated from renal cell carcinoma. Diagnosis of Ewing sarcoma is done using histopathology, IHC, and cytogenetic study. Early diagnosis helps in initiation of surgery, chemotherapy, and radiotherapy and helps in increasing the survival rate.

Merkel cell carcinoma - particularities and morphological aspect of a unique and rare entity

Abstract Introduction: Merkel cell carcinoma is a very rare malignant neoplasm which presents high aggressivity, high recurrence rate and has meta-static potential. Our purpose is to present the histological and immunohistochemical particularities of Merkel Cell Carcinoma while reviewing potential differential diagnoses and challenges that we can encounter in daily practice. Case presentation: We present the case of an 86-year-old female patient who presented with a nodular tumour located in the left forearm, raising suspicion of a soft tissue tumour. The histological appearance of this unique type of cancer is highlighted on the Haematoxylin-eosin stain as a solid tumour composed of nests and chords of monomorphic cells. The nuclei of these tumoral cells appear characteristically as enlarged with dispersed chromatin. The immunohistochemical reactions have been performed and it was observed that the tumoral cells exhibited positivity for synaptophysin, CD56, NSE, EMA, as well as a “dot-like” expression for CK20. These histopathological and immunohistochemical features were consistent with a diagnosis of MCC, stage pT3, based on the assessment of tumour size. Conclusions: Sometimes, differentiating this tumour from other primary malignant neoplasms of the skin or even cutaneous metastases can be difficult. Immunohistochemistry remains the most important tool of diagnosis, especially for differentiating this neoplasm from metastatic neuroendocrine tumours that can affect the skin.

Abstract PO2-20-09: Hiding in plain sight: A heterogeneous response in a patient with metastatic HR+/HER2- breast cancer

Abstract INTRODUCTION: Metastatic breast cancer is an infamously heterogeneous disease—characterized by a range of clinical presentations and treatment responses. In light of this heterogeneity, ASCO guidelines recommend patients with new, accessible metastatic tumors undergo a biopsy to inform treatment decisions. Here, we present a patient with HR+/HER2- disease with a long history of unusually heterogeneous responses—and a repeat metastatic biopsy that provided an answer. CASE: A 55-year-old woman presented for consultation of treatment-refractory metastatic breast cancer. She was originally diagnosed with a right-sided Stage III HR+/HER2- invasive ductal carcinoma (IDC) at the age of 33. Upon staging, she was incidentally found to have a right lower-lobe lung carcinoid tumor that was removed by lobectomy. She underwent a partial mastectomy, axillary lymph node dissection, followed by adjuvant chemo- and radiation therapy. She tolerated one week of tamoxifen which was discontinued due to adverse effects. Fifteen years later, screening mammography revealed a suspicious lesion in the right breast—biopsy consistent with a new IDC. She underwent bilateral mastectomies which showed a pT1cNxM0 G2 IDC with associated DCIS (ER+/PR+/HER2 IHC 2+, FISH-negative, Oncotype RS 12). Genetic testing was negative. The patient trialed adjuvant tamoxifen, which was discontinued due to repeat adverse effects. Two years later, rising tumor markers prompted restaging scans that demonstrated an enlarging liver lesion. Liver biopsy was consistent with metastatic adenocarcinoma of the breast (ER+/PR+/HER2 IHC 0), GATA3 positive. Patient was started on letrozole with lupron and palbociclib with disease control for two years until progression in the bone, prompting a switch of letrozole to fulvestrant with continued palbociclib. Her disease was stable for two additional years until progression of multiple liver lesions. She was then started on single-agent paclitaxel. At this point, she was seen in our office for consultation and next-line therapy options. Repeat staging scans showed heterogeneous response in the liver with overall progression. ctDNA testing revealed a mutation in MEN1 (p.Q354*, 2.8% VAF) without other actionable alterations. Patient opted to enroll into a clinical trial of an experimental ER-antagonist but experienced progression of her liver lesions on first staging scans. A second liver biopsy was performed on a progressive lesion which showed ER-/PR-/HER2- disease. She opted to enroll into a Phase 1b/2 trial with sacituzumab govitecan-hziy in combination with a PARPi. Staging scans again showed a mixed response in the liver. Given a history of mixed responses and discordant receptor staining, the differential diagnosis included loss of hormone receptor expression in the breast carcinoma versus metastases from an occult neoplasm. Additional immunohistochemical studies were performed on a subsequent liver biopsy showing positivity for chromogranin, synaptophysin, and INSM1, and negative results for ER, PR, GATA3, and TRPS1. Next-generation sequencing of the progressive lesion revealed a MEN1 SNV (p.Q354*, VAF 82%) as well as loss of 11q (MEN1 locus) suggestive of biallelic loss of MEN1—providing molecular evidence of a metastatic carcinoid tumor. A history of mixed response in the liver was concluded to be two coexisting neoplasms—a metastatic HR+/HER2- breast cancer as well as a late recurrence of a right-lower lobe carcinoid tumor from 22 years prior. DISCUSSION: The unanticipated discovery of an occult, coexisting neoplasm in the setting of a metastatic HR+/HER2- breast cancer illustrates the value of meticulous pathological review, repeat molecular testing and the use of next-generation diagnostic tools such as tumor sequencing in the advanced setting—particularly when a clinical story defies conventional expectations—to personalize care and optimize oncologic management in the face of complex biology. Citation Format: Nolan Priedigkeit, Jane Brock, Olivia Cunningham, Molly Skeffington, Melissa Hughes, Nancy Lin, Susan Lester, Heather Parsons. Hiding in plain sight: A heterogeneous response in a patient with metastatic HR+/HER2- breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-20-09.

Presacral Neuroendocrine Neoplasms: A Multi-site Review of Surgical Outcomes.

Presacral neuroendocrine neoplasms (PNENs) are rare tumors, with limited data on management and outcomes. A retrospective review of institutional medical records was conducted to identify all patients with PNENs between 2008 and 2022. Data collection included demographics, symptoms, imaging, surgical approaches, pathology, complications, and long-term outcomes. Twelve patients were identified; two-thirds were female, averaging 44.8years of age, and, for the most part, presenting with back pain, constipation, and abdominal discomfort. Preoperative imaging included computed tomography scans and magnetic resonance images, with somatostatin receptor imaging and biopsies being common. Half of the patients had metastatic disease on presentation. Surgical approach varied, with anterior, posterior, and combined techniques used, often involving muscle transection and coccygectomy. Short-term complications affected one-quarter of patients. Pathologically, PNENs were mainly well-differentiated grade 2 tumors with positive synaptophysin and chromogranin A. Associated anomalies were common, with tail-gut cysts prevalent. Mean tumor diameter was 6.3cm. Four patients received long-term adjuvant therapy. Disease progression necessitated additional interventions, including surgery and various chemotherapy regimens. Skeletal, liver, thyroid, lung, and pancreatic metastases occurred during follow-up, with no mortality reported. Kaplan-Meier analysis showed a 5-year local recurrence rate of 23.8%, disease progression rate of 14.3%, and de novo metastases rate of 30%. The study underscores the complex management of PNENs and emphasizes the need for multicenter research to better understand and manage these tumors. It provides valuable insights into surgical outcomes, recurrence rates, and overall survival, guiding future treatment strategies for PNEN patients.

Ovarian endometrioid carcinoma with a sex cord-like pattern: a morphological, immunohistochemical, and molecular analysis.

Sex cord-like endometrioid carcinoma (SCLEC) is an uncommon entity which may constitute a diagnostic challenge. This study aimed to perform a clinicopathological, immunohistochemical, and molecular reappraisal of ovarian SCLEC. Consecutive ovarian SCLECs cases from a single institution were reviewed during a 13-year period. Twenty-three immunohistochemical markers were tested; 10 genes were analyzed by next-generation sequencing. Nine cases of ovarian SCLEC were identified. Mean patient age was 65.7years; three cases showed extraovarian extension. Architectural pattern included sertoliform (n = 2), granulosa-like (n = 2), and mixed granulosa-like/sertoliform (n = 5). Eosinophilic changes accompanied by increased nuclear atypia were observed in four tumors. Endometrioid features (glands, squamous/morular differentiation) were observed in six cases. Most tumors were positive for cytokeratin-7 (8/9), EMA (9/9), estrogen and progesterone receptor (9/9), CD10 (7/9, including a luminal pattern reminiscent of mesonephric neoplasms), nuclear β-catenin (8/9), and CDX2 (8/9). A minority of cases showed block-type p16 pattern (2/9), PAX8-positivity (3/9), and non-diffuse positivity for WT1 (1/9), inhibin (1/9), chromogranin (1/9), and synaptophysin (2/9). All cases were negative for GATA3, TTF1, calretinin, and SF1. Ki67 range was 15-90%. Six cases showed CTNNB1 exon 3 mutation. Eight cases were of "no specific molecular profile" (NSMP) and one was p53-abnormal. In conclusion, SCLECs frequently exhibit a mixed sertoliform/granulosa-like architecture and express epithelial markers, hormone receptors, nuclear β-catenin, and CDX2, with luminal CD10 positivity and CTNNB1 mutations. PAX8 expression is often lost, while other mesonephric, sex cord, and neuroendocrine markers are negative.

Thoracic SMARCA4-deficient undifferentiated tumor: A clinicopathological and prognostic analysis of 35 cases and immunotherapy efficacy

BackgroundThoracic SMARCA4-deficient undifferentiated tumor (SMARCA4-UT) is a recently recognized distinct clinicopathological entity according to the fifth edition of the 2021 World Health Organization Classification (WHO) for thoracic tumors. Thoracic SMARCA4-UTs are diagnostically challenging to diagnose, especially on small biopsies. MethodsWe identified 35 thoracic SMARCA4-UTs from the Department of Pathology of West China Hospital, Sichuan University, between January 2017 and December 2022. In the present study, we summarized the clinicopathological features, prognostic significance and immunotherapy efficacy of thoracic SMARCA4-UTs. ResultsAll 35 patients were male, and 88.6 % were smokers. The left upper lobe (25.7 %) and mediastinum (20.0 %) were the most affected sites. 17.1 % of the patients received surgical treatment. 30.4 % of the patients were stage III, and 69.6 % were stage IV. Solid architecture (100 %), rhabdoid morphology (51.4 %) and necrosis (42.9 %) were the common histological features. Immunohistochemical staining revealed CD34 and synaptophysin positivity in most patients (76.9 % and 65.2 %, respectively). Patients had unfavorable outcomes. Patients who received immunotherapy had better OS and PFS than those who did not (p = 0.007 and p = 0.02, respectively). Five patients were evaluated for immunotherapy efficacy, and four of those patients were negative expression of PD-L1. Cases 1–4 presented TIL counts ranging from 20 to 1000/HPF. Case 5 presented TIL counts of 5–10/HPF. Mutations in SMARCA4 were confirmed in cases 4 and 5, and the TMB was 5.98 and 5.03 mutations/Mb, respectively. Case 1 achieved a CR, cases 2–4 achieved a PR, and case 5 had a PD. Five patients who received immunotherapy were all alive, with OS ranging from 10.7 to 33.6 months. ConclusionsThoracic SMARCA4-UTs exhibited an aggressive clinical course, presented solid architecture with or without necrosis and/or rhabdoid morphology, and frequently expressed CD34 and synaptophysin. Some thoracic SMARCA4-UTs appear to be associated with responsiveness to immunotherapy, suggesting the need for validation in larger series.

Клинико-морфологическое наблюдение высокодифференцированной нейроэндокринной опухоли головки поджелудочной железы на фоне синдрома фон Гиппеля–Линдау

Von Hippel-Lindau (VHL) disease is a rare autosomal dominant genetic disease characterized by the formation of benign and malignant tumors. From 10 to 20% of patients develop a pancreatic neuroendocrine tumor (panNET). This article presents a clinical and morphological case that describes a well-differentiated neuroendocrine tumor of the pancreatic head accompanied by VHL syndrome. Positive Synaptophysin and Chromagranin A staining of tumor cells confirmed the diagnosis. The proliferation index (Ki-67) was less than 3%. In addition, serous cystadenoma without signs of neuroendocrine differentiation was found in the pancreatic tail, which was confirmed by positive reaction with antibodies to CA IX and MUC6 and a negative reaction with antibodies to Synapthophysin in the epithelial cells. Keywords: von Hippel-Lindau syndrome, neuroendocrine tumor, pancreas, immunohistochemical study

A Rare Case of Embryonal Rhabdomyosarcoma of Pineal Gland in An Adult Male

Abstract Introduction/Objective Rhabdomyosarcoma (RMS), mesenchymal derived tumor, is predominantly diagnosed in the pediatric population but may present at any age. Less than 1% of all adult solid malignant cancers are sarcomas, and rhabdomyosarcoma comprises <0.001% of adult sarcomas. Primary intracranial RMS is rare and has been reported in the cerebrum, cerebellum, brainstem, and the meninges. The occurrence of a primary intracranial RMS arising from the pineal gland is exceedingly rare. Methods/Case Report An adult male presented to the ED with complaint of several months of headaches, progressive confusion, forgetfulness and most recently difficulty in finding words. CT scan showed a large mass arising from the pineal gland causing obstructive hydrocephalus. Subsequently, the patient underwent excisional biopsy. The histopathology examination revealed small round basophilic cells and large polygonal cells with large eccentric nuclei and prominent nucleoli, abundant eosinophilic cytoplasm containing globular paranuclear eosinophilic inclusions, characteristic of rhabdoid cells. Immunohistochemical (IHC) showed tumor cells are positive for Desmin, MyoD1, CK8/18, INI1 (hSNF5; SMARCB1) with retained nuclear expression and faint positivity for Synaptophysin and focally positivity for Neurofilament. The tumor cells showed negative staining for Pankeratin, SOX10, Oct4, SALL4, INSM1, LCA AND CD30, which excluded the possibility of Germ cell tumor and Pineoblastoma. The case was finalized as primary malignant neoplasm, consistent with Embryonal Rhabdomyosarcoma of pineal gland. Results (if a Case Study enter NA) NA Conclusion This case highlights the rare occurrence of rhabdomyosarcoma originating from the pineal gland in an adult male. Morphologic and immunohistochemical findings were consistent with embryonal rhabdomyosarcoma. Since primary rhabdomyosarcoma of the pineal gland is rare, this case contributes to the limited body of literature on such cases. It underscores the importance of considering unusual entities in intracranial tumors. The distinct morphology and the use of IHC aids in diagnosing this rare entity.

Thoracic SMARCA4-deficient undifferentiated tumor: A rare entity and challenging diagnosis

Abstract Introduction/Objective Thoracic SMARCA4-deficient undifferentiated tumor is a high-grade malignant neoplasm that frequently shows undifferentiated morphology and deficiency of SMARCA4. There is limited data in literature for this entity. The purpose of this report is to describe a case of this entity and to emphasize the importance of keep this entity in mind when dealing with poorly differentiated thoracic / lung tumors. Methods/Case Report A 49-year-old female with 7.5 pack years smoking history presented with a right shoulder pain. A chest x-ray showed rounded density in the right lung apex. This was followed by a CT chest which revealed a 5.6 cm mass with local destruction of the adjacent right third rib suggestive of a chest wall invasion. Also, hilar and paratracheal lymphadenopathy were noted. Subsequently the patient underwent a right upper lobe biopsy which showed diffuse discohesive sheets of moderately pleomorphic large epithelioid cells with vesicular chromatin, focal rhabdoid morphology, frequent mitoses, and extensive necrosis. Immunochemical staining showed the tumor cells to be positive for Cam 5.2, pancytokeratin (focal, weak), synaptophysin, p53 and TTF-1 (focal, weak) and negative for Napsin, SOX-10, CD45, chromogranin, INSM1, p40, CK7, and CK20. Ki-67 proliferation index was 40-50%. Tumor cells had intact expression of RB and were negative BRG1 (SMARCA4). Therefore, diagnosis of thoracic SMARCA4- deficient undifferentiated tumor was rendered. Next generation sequencing showed pathogenic variants in TP53, CDKN2A, and APC genes and likely pathogenic variants in ATR, SMARCA4, and BCOR genes. The patient received carbotaxol and radiation therapy and is alive with metastatic disease 4 months after initial diagnosis. Results (if a Case Study enter NA) NA Conclusion SMARCA4-deficient undifferentiated tumor is an aggressive malignancy that shows undifferentiated histology with frequent synaptophysin positivity and negativity for other neuroendocrine markers. Pathologists need to keep this entity in their differential when dealing with poorly to undifferentiated thoracic / lung tumors and appropriate immunohistochemical staining can clinch the diagnosis.

THU094 Multiple Endocrine Neoplasia Type 1 Tumor Recurrence After Loss To Follow Up

Abstract Disclosure: S.J. Sternlieb: None. K.G. Romo: None. R.S. Boothe: None. D. Englert: None. N. Manuel: None. Q.Z. Iqbal: None. Multiple Endocrine Neoplasia Type 1 Tumor Recurrence After Loss to Follow-up Sternlieb, S. J., Romo, K.G., Boothe, R., Manuel, N., Iqbal, Q.Z., Grissett, B., Englert, D. Background: MEN1 is a rare, autosomal dominant tumor disorder due to mutations in the MEN1 tumor suppressor gene. It is characterized by parathyroid, enteropancreatic and pituitary tumors. We present a young woman with MEN1 with prolactinoma, primary hyperparathyroidism and multiple pancreatic neuroendocrine tumors. Clinical Case: A 30-year-old woman with MEN1 presented with complaints of abdominal pain and GI bleeding (GIB). She was diagnosed with a prolactinoma at age 14 after presenting for primary amenorrhea and galactorrhea. She didn’t tolerate medical therapy with bromocriptine or cabergoline and required transphenoidal resection. At age 19, she presented with hypoglycemia and was found to have multiple pancreatic neuroendocrine tumors (NET) as well as a left (L) adrenal gland tumor. She underwent distal pancreatectomy and L adrenalectomy. Ten tumors in the pancreas stained variably for insulin, glucagon, gastrin and VIP. Multiple cortical adenomas were found in the adrenal gland. Post-operatively she developed a spinal cord hematoma related to placement of an epidural catheter for pain control, which led to permanent paraplegia. At age 21, she was diagnosed with primary hyperparathyroidism. She underwent left parathyroidectomy, then was lost to follow-up for 9 years. EGD showed multiple superficial duodenal ulcers. MRI brain identified a right (R) cavernous sinus mass inseparable from the R pituitary. CT abdomen showed a pancreatic head mass. Given the concern for neuroendocrine etiology, she underwent an EUS showing a pancreatic mass and a liver mass. Pancreatic mass pathology confirmed low-grade NET with Ki67 proliferation rate <1%, positive synaptophysin and chromogranin staining. After multidisciplinary discussion, the consensus was to continue PPI and sucralfate for GI ulcers, start lanreotide, and obtain somatostatin receptor scintigraphy. Surgery was not recommended unless significant GIB occurred on maximal therapy. She was referred to follow-up with GI, endocrinology, and NSGY. Since discharge, she has presented several times to other hospitals for abdominal pain, but has not adhered to follow-up. Conclusions: This case of recurrent neuroendocrine and pituitary tumors despite prior resections demonstrates the consequences of prolonged loss to follow-up with MEN1. Without routine surveillance, recurrence is likely. This patient lives in a rural area with lack of access to nearby subspecialty care, which is a barrier. More resources are needed to support patients with social barriers and progressive endocrinopathies. Key words: MEN1, prolactinoma, gastrinoma, NET, health care barriers Presentation: Thursday, June 15, 2023

Intracranial dissemination in a primary small cell carcinoma of the brain: a case report and literature review.

Primary intracranial small cell carcinoma (SCC) is extremely rare with only 8 previously reported cases. We describe a case of primary intracranial SCC with intracranial metastasis. A 46-year-old man presented with decreased vision and a red and swollen left eye. Brain magnetic resonance imaging (MRI) revealed a heterogeneously enhanced tumor on the left frontal lobe. Preoperative systemic computed tomography (CT), MRI, and positron emission tomography (PET)-CT revealed no extracranial tumors. The tumor on the left frontal lobe was excised. Immunohistochemical staining on the excision showed positivity for CD56, synaptophysin (Syn), cytokeratin (CK), and Ki-67 (30%), and negativity for thyroid transcriptional factor-1 (TTF-1), glial fibrillary acidic protein (GFAP), B-cell lymphoma 6 (Bcl-6), multiple myeloma oncogene 1 (MUM-1), C-Myc, Vimentin, P40, P53, CK7, CD3, CD5, CD20, CD79a, CD10, and CD23. The pathological examination strongly suggested that the tumor was a primary intracranial SCC. One year after the surgery, the patient was readmitted with slurred speech and slow movements. Three well-defined tumors were found in the left upper frontal lobe by brain MRI. Tumor resection was then performed. Further immunohistochemical examination of the excised tissue displayed the same pattern as previously, indicating the recurrence of intracranial SCC in the left frontal lobe. The patient received adjuvant chemotherapy and radiotherapy after the tumor resection. At the 2-year follow-up, he remained asymptomatic.

P16.01.A THE CASE OF AGGRESSIVE DIFFUSE LEPTOMENINGEAL GLIONEURONAL TUMOR IN ADULT TREATED WITH CRANIOSPINAL IRRADIATION AND TEMOZOLOMIDE

Abstract BACKGROUND Diffuse leptomeningeal glioneuronal tumor (DLGNT) is a rare tumor, which was introduced as a separate entity in the 2016 World Health Organization classification of central nervous system tumors. It is most common in pediatric age, but very rare in adults. Literature demonstrates limited reports regarding treatment strategy in adult. We present a case of young female affected by DLGNT with aggressive behavior. MATERIAL AND METHODS A 28-year-old woman presented with severe headache and vomiting. Brain MRI showed diffuse leptomeningeal enhancement with hydrocephalus. At first, she was under suspicion of tuberculosis meningitis with mild increased protein level in CSF study. Her symptom rapidly improved after ventriculoperitoneal shunt and she started anti-tuberculosis medication. Despite 8-month of medication, her neurological status gradually deteriorated with paraparesis and follow-up MR images showed progression of disease. She underwent open biopsy of superficial brain lesions. RESULTS Intraoperatively, multiple nodular masses were attached inner side of dura mater and diffuse adhesion on subarachnoid space of brain surface. Histological examination revealed small round cells with oligodendroglial-like aspects. Immunohistochemistry showed positivity for Olig2, synaptophysin and S100. Chromosome 1p deletion was confirmed by FISH. Next-generation sequencing profile disclosed mutation of H3K28M, FGFR1 and ATRX. Diagnosis was consistent with DLGNT. She received craniospinal irradiation of 36 Gy in 20 fractions, then started chemotherapy with temozolomide (TMZ) at a dose 200mg/m2/day for 5 days in 4 weeks. After 4 cycles of TMZ, MR images demonstrated stable disease. CONCLUSION DLGNT is a very rare tumor in adult. Diagnosis needed high level of suspicion and histological confirmation. We present a very rare adult DLGNT patient with aggressive clinical features who showed stable state treated with craniospinal irradiation and TMZ chemotherapy.

Neuroendocrine Marker Expression in Primary Non-neuroendocrine Epithelial Tumors of the Ovary: A Study of 551 Cases.

Expression of neuroendocrine (NE) markers in primary ovarian non-NE epithelial tumors has rarely been evaluated. The aim of our study was to evaluate the expression of the most widely used NE markers in these neoplasms and to determine any prognostic significance of NE marker expression. The cohort consisted of 551 primary ovarian tumors, including serous borderline tumors, low-grade serous carcinomas, high-grade serous carcinomas (HGSC), clear cell carcinomas, endometroid carcinomas, mucinous borderline tumors, and mucinous carcinomas. Immunohistochemical analysis was performed using antibodies against INSM1, synaptophysin, chromogranin, and CD56 on tissue microarray. Positivity for INSM1, synaptophysin, chromogranin, and CD56 was most frequently observed in mucinous tumors (48.7%, 26.0%, 41.5%, and 100%, respectively). The positivity for these NE markers was mostly restricted to nonmucinous elements distributed throughout the tumor. The mucinous borderline tumor and mucinous carcinomas groups had similar proportions of positivity (mucinous borderline tumor: 53%, mucinous carcinomas: 39%). In the other tumor types, except for HGSC, there was only focal expression (5%-10%) or negativity for NE markers. HGSC showed high CD56 expression (in 26% of cases). Survival analysis was only performed for CD56 in HGSC as this was the only group with sufficient positive cases, and it showed no prognostic significance. Except for mucinous tumors, expression of NE markers in non-NE ovarian epithelial tumors is low. CD56 expression in HGSC occurs frequently but is without diagnostic or prognostic value.

Thoracic SMARCA4-deficient undifferentiated tumor: A clinicopathologic study.

e14642 Background: Thoracic SMARCA4-deficient undifferentiated tumor is a high-grade malignant neoplasm that frequently shows undifferentiated morphology and deficiency of SMARCA4. There is limited data in literature for this entity. The purpose of this report is to describe clinicopathologic features of this rare tumor in a series of 5 patients, diagnosed and treated at our institution. Methods: After approval from institutional review board, pathology department archive was searched for the patients with diagnosis of Thoracic SMARCA4-deficient undifferentiated tumor from January 2020 to December 2022. Data such as patient demographics, pathologic features including immunohistochemical stains, treatment and clinical outcome were collected. Results: Among 5 patients, 3 were male and 2 were female. Median age was 62 years (range 49 to 77 years). In three patients the primary site of the tumor was lung. One patient had tumor of the gastroesophageal junction while one patient had epicenter of the tumor in the paraspinous muscle. Diagnosis was made on biopsy specimen in all cases. All tumor showed undifferentiated histologic appearance. Rare cells with keratin positivity were observed in 2 specimens while 3 were completely negative for keratin stains. Focal TTF1 positivity was observed in one specimen while 4 were negative. Among neuroendocrine markers performed on variable number of cases, synaptophysin was positive in 4/4 cases while chromogranin was negative in 2/2 cases and INSM1 was negative in 1/1 case. PD-L1 (Dako 22C3) was performed on two specimens and showed less than 1% tumor cells to be positive. Next generation sequencing was performed on one specimen and showed pathogenic variants in TP53, CDKN2A, and APC genes and likely pathogenic variants in ATR, SMARCA4, and BCOR genes. Two patients received carbotaxol and radiation, one patient received FOLFOX, nivolumab and radiation, 1 patient pursued hospice care and 1 patient lost follow up. Two patients died 2 and 7 months after diagnosis. One patient is alive with metastatic disease 4 months after initial diagnosis. Conclusions: SMARCA4-deficient undifferentiated tumor is an aggressive malignancy that shows undifferentiated histology with synaptophysin positivity. From a diagnosis standpoint, Pathologists need to keep this entity in mind while working up tumors showing poorly differentiated to undifferentiated histology that are negative for most immunohistochemical markers. From clinical standpoint there is need to develop targeted therapy for this aggressive tumor.

Combined tubular adenocarcinoma, neuroendocrine carcinoma and adenocarcinoma with enteroblastic differentiation arising in Barrett esophagus

Adenocarcinoma (AC) with neuroendocrine carcinoma (NEC) or enteroblastic (ENT) differentiation rarely develops in Barrett’s esophagus (BE). A 76-year-old man was diagnosed with Barrett’s AC (cT1bN0M0) and underwent thoracoscopic esophagectomy. A type 0-IIc + 0-Is lesion measuring 26 × 21 mm was macroscopically observed on a background of long segment BE (pT1bN0M0). The tumor comprised three different histological types of carcinoma (NEC, AC with ENT differentiation and moderately differentiated AC). NEC showed positivity for synaptophysin, chromogranin A and insulinoma-associated protein 1 with a Ki-67 index of 60.6%. ENT tumors were immunopositive for AFP and sal-like protein 4, and focally immunopositive for human chorionic gonadotrophin. The amounts of NEC, ENT and AC were 40%, 40% and 20%, respectively. p53 expression was positive throughout the tumor. Rb expression was negative at the NEC, but positive at the ENT and AC. CD4 and CD8 densities were lower in the NEC segment than in the AC and ENT segments, and PD-L1 expression was negative throughout the tumor. Early cancer arising in BE with a combination of tubular AC, ENT tumors and NEC is very rare. Our observations might contribute to understanding the carcinogenetic pathways and tumor microenvironment of NEC and ENT tumors.

Establishment of patient-derived xenografts of retinoblastoma and choroidal melanoma on the avian chorioallantoic membrane.

To develop a viable in vivo chorioallantoic membrane (CAM) model to study the growth and invasion of patient-derived retinoblastoma (RB) and choroidal melanoma (CM) xenografts (PDXs). The study utilizes primary tumor samples instead of cancer cell lines, which provides a more authentic representation of tumors due to conserved morphology and heterogeneity. Fertilized chicken eggs were procured, windowed, and their CAM layers were dropped. On embryonic development day (EDD) 10, freshly cut patient-derived CM and RB tumors were implanted on the CAM layer and the setup was incubated for 7 days. The tumor-embedded CAM layer was harvested on EDD 17, and the extracted tumor samples were subjected to hematoxylin and eosin staining and immunohistochemical analysis to evaluate the extent of tumor invasion. Significant changes in the vascularity around the RB and CM PDXs were observed, indicating an angiogenic environment. The cross-sectional histological view of the tumor implant site revealed the invasion of both the tumors into the CAM mesoderm. Invasion of CM into CAM mesoderm was visualized in the form of pigmented nodules, and that of RB was indicated by synaptophysin and Ki-67 positivity in Immunohistochemistry (IHC). The CAM xenograft model was successfully able to support the growth of CM and RB PDXs and their invasion in CAM, thus presenting as a feasible alternative to mammalian models for studying tumorigenicity and invasiveness of ocular tumors. Moreover, this model can further be utilized to develop personalized medicine by inoculating patient-specific tumors for preclinical drug screening.