Cm In Greatest Dimension Research Articles

Minimally invasive resection of a giant esophageal schwannoma

Benign tumors of the esophagus are uncommon, and primary esophageal schwannoma of the esophagus is even rarer, accounting for 2% of cases. Less than 30 cases have been reported in the literature. Here we report a case of a young man with a symptomatic giant esophageal schwannoma, which was completely removed by laparoscopic three-staged esophagectomy. This is the first case of such a large lesion being removed by a minimally invasive approach. Our patient was a 22-year-old male, presented with dysphagia and dyspnea for five years. An endoscopy and CT scan suggested a giant leiomyoma. Postoperative biopsy revealed a primary esophageal schwannoma. We present our case of benign esophageal tumor measuring about 10.5 cm in greatest dimension. This is the first schwannoma resection performed with the Mckeown technique among the limited case reports in the literature. Esophageal schwannoma must be kept as a possible diagnosis in patients presenting with benign esophageal tumors. Esophagectomy is the mainstay of treatment for giant esophageal schwannomas. Minimally invasive esophagectomy can be safely performed for giant benign esophageal tumors. doi: https://doi.org/10.12669/pjms.40.10.8824 How to cite this: Qureshi S, Khan S, Abbasi WA, Sohail M. Minimally invasive resection of a giant esophageal schwannoma. Pak J Med Sci. 2024;40(10):2447-2450. doi: https://doi.org/10.12669/pjms.40.10.8824 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Case Report of Rectosigmoid Vascular Malformation

Abstract Introduction/Objective Gastrointestinal (GI) vascular malformations and hemangiomas, although infrequently encountered, can present with similar clinical symptoms as other more common causes of chronic hematochezia, such as hemorrhoids or inflammatory bowel disease (IBD, ex. Crohn’s disease, ulcerative colitis). Whereas hemangiomas are benign vascular tumors that grow quickly and often involute, vascular malformations consist of abnormal vasculature that grow in size as the individual ages without regression. Gastrointestinal vascular malformations can result in pain secondary to applied pressure on nearby tissues/organs and induce a chronic anemic state secondary to ongoing hematochezia. As surgery or sclerotherapy can often treat the condition, proper diagnosis is critical as it can impact treatment and quality of life. Among GI vascular malformations, rectosigmoid vascular malformations are uncommon, making up 5% of lower limb vascular malformations examined in recent published literature. In this case report, we highlight a case of rectosigmoid vascular malformation. Methods/Case Report A 41-year-old female, initially treated for inflammatory bowel disease (IBD), presents with multiple bloody bowel movements a day accompanied by nausea secondary to chronic proctosigmoiditis refractory to medications traditionally used in IBD: mesalamine derivatives, systemic corticosteroid, and biologics. While colonoscopy demonstrated some features suggestive of ulcerative colitis, CT and MR enterography showed severe rectal wall thickening with phleboliths, which was unchanged over many years, suggestive of a vascular malformation such as a hemangioma. Following rectosigmoid colon resection, a diagnosis of a 9 cm rectosigmoid vascular malformation was made, showing extensive bowel wall involvement by the malformed vasculature. On follow-up, the patient is doing well, and her symptoms have completely resolved. Results (if a Case Study enter NA) NA Conclusion Vascular malformations can be classified into various subtypes (capillary, venous, arterial, lymphatics, etc), found throughout the body, and vary in size. Our case consists of a mixed nature (artery, vein, and lymphatics), notable size (9.0 cm in greatest dimension) with extensive bowel wall involvement, and an unusual location (rectosigmoid region). This case represents an uncommon presentation of this entity, which appears to be clinically challenging. Though uncommon, this diagnosis should be on the differential of unusual etiologies of overt lower GI bleeding.

Giant pilomatricoma with atypical features: report of a case of aggressive pilomatricoma in an adult

Abstract Introduction/Objective Pilomatricoma, also known as pilomatrixoma or calcifying epithelioma of Malherbe, is a relatively common, benign tumor of the hair matrix. It typically presents as a small (~1cm), dermal based mass in the head and neck region of children and young adults (under 20 years) with predominance for males, but can occur in any age. In contrast, malignant pilomatricoma is typically larger (1 to 10 cm) and occurs later in life (50-60 years). Aggressive pilomatricoma is a variant of pilomatricoma that tends to occur in children and demonstrates atypical features such as increased matrical cells and nuclear atypia, but insufficient for a classification as pilomatrical carcinoma. Here, we presented a case of a large (14.5 cm) aggressive/atypical pilomatricoma that occurred in an adult. Methods/Case Report A 45 year-old-female presented to the emergency department with a posterior neck mass which has been slowly enlarging for years. Recently, it became painful with sanguineous discharge which prompted her to seek medical attention. CT scan revealed a lobulated, pedunculated mass with fat and fluid components. An excision was performed. Gross examination revealed an ulcerated mass measured 14.5 cm in greatest dimension. Scattered calcifications were present. Microscopically, nests of basaloid cells with scattered shadow cells are present consistent with matrical differentiation. A multinodular growth pattern with central necrosis was evident. Nuclear atypia characterized by prominent nucleoli and nuclear overlapping was identified. Results (if a Case Study enter NA) NA Conclusion Histopathologic criteria to reliably differentiate between benign and malignant pilomatrical tumors are not well-established. Tumor ulceration, asymmetry, irregular borders, multinodular growth pattern, marked cytologic atypia, prominent necrosis, lymphovascular invasion, and perineural invasion may be used in favor of malignancy. Our case showed focal confluent necrosis, ulceration, multinodular growth pattern, and cellular atypia but lacked other features that indicative of unequivocal malignancy. The resection margins were negative for tumor. Clinical followup was negative for signs of recurrence or metastasis after two years. We presented this case to show the large size that aggressive pilomatricoma can reach and to emphasize the difficulty in differentiating benign from malignant pilomatrical tumors in borderline cases.

The lateral based nasopharyngeal flap: A novel vascularized flap for skull base reconstruction.

As the indications for endoscopic skull base approaches have increased, so has the need for more versatile vascularized flaps for skull base reconstruction. Here, we describe a novel lateral based nasopharyngeal flap (LNPF). Two cadaver heads were dissected to elucidate flap anatomy, dimensions, and technique. A retrospective review was performed on two cases where LNPF was used to repair CSF leaks in the nasopharyngeal area, and outcomes reported. The LNPF is an ascending pharyngeal artery myomucosal flap that includes the nasopharyngeal mucosa and the superior pharyngeal constrictor muscle. The flap was 1.2 × 2.2 cm in greatest dimensions. The LNPF was used for salvage CSF leak repair in two cases: one clival and one tubal. Both patients had resolution of leak at 7 months follow-up. The LNPF is a novel flap with reconstruction potential for the nasopharynx, including the lower clivus and the eustachian tube.

Seromucinous borderline tumor-associated high-grade ovarian cancers

We present 6 high grade ovarian carcinomas that were associated with seromucinous borderline tumors. Patients ranged in age from 26 to 66 years. All cancers appeared as solid regions within otherwise paucicystic tumors that measured from 4.2 cm to 14.0 cm in greatest dimension. Five of the 6 tumors were bilateral, and endometriosis was seen in 4 of the tumors. Clinical data, with follow up periods ranging from 0 to 40 months, was available for all patients. Four patients died of their disease and two had recurrent disease at the time of this review. All tumors exhibited a low-grade carcinoma component, which is consistent with ovarian cancers developing in a progressive adenoma to carcinoma sequence (so-called type I ovarian cancers). Two of the associated low-grade/borderline tumors had focal serous characteristics with WT1+ epithelial cell clustering. High-grade tumors exhibited an array of cell types expressing endometrioid, undifferentiated, serous, clear cell, and mucinous features that were at times mixed within the same tumor. Five cancers were focally WT1+; two showed admixed lowgrade serous features and one showed a high-grade serous adenocarcinoma with transitional features. Two cancers had mucinous features (one with focal CK20 and CDX2 immunohistochemical staining and one only with focal CDX2 immunohistochemical staining). All the high-grade tumors showed a mutated-pattern of p53 nuclear staining with >75% 2-3+ staining. We conclude that seromucinous borderline tumors need to be extensively sampled. Cyst wall membrane rolls are important to evaluate since they may reveal persisting endometriosis and solid regions most likely harbor a high-grade tumor. Identifying high-grade cancer within a seromucinous borderline tumor is important because, although seromucinous borderline tumors and their oftassociated low-grade endometrioid cancers have favorable outcomes, tumors harboring a high-grade component are aggressive and may eventuate in patient death.

A Rare Presentation of Primary Thymic Small Cell Carcinoma Found after Trauma: A Case Report

Thymic small cell carcinoma is an exceedingly rare diagnosis with undefined treatment options and, typically, poor prognosis. A 69-year-old female presented to the Emergency Department with chest pain and was found on Computed Tomography (CT) to have a multilobulated cystic mass in the anterior mediastinum. Magnetic Resonance Imaging (MRI) demonstrated a 7 x 8 x 8 cm mediastinal mass suspicious for thymoma. Biopsies of enlarged lymph nodes in levels 4L and 7 were negative for malignancy. The patient was taken for surgical resection of the mediastinal mass. After standard sternotomy, the mass was noted to be contiguous with the thymus. The specimen was removed en bloc and surgical pathology revealed high grade neuroendocrine carcinoma, measuring 9.0 cm in greatest dimension, consistent with small cell carcinoma of the thymus. Fibrous adhesions to the lung were noted but all margins and lymph nodes were negative for malignancy. Brain MRI was unremarkable and multidisciplinary tumor board decided to proceed with adjuvant chemotherapy. Patient is currently doing well without symptoms of recurrence one year post-operatively.

Aggressive angiomyxoma of female pelvis and perineum: Retrospective study of 17 cases

ObjectiveAggressive angiomyxoma is an uncommon mesenchymal neoplasm characterized by a high recurrence rate, usually observed in the lower genital tract of women during their reproductive age. Study designSeventeen cases of aggressive angiomyxoma confirmed by pathology from January 2007 to December 2021 in Beijing Chao-yang Hospital were included. We collected clinical data and summarized the clinical and immunohistochemical features. ResultsAll seventeen included patients were females, aged between 23 and 57 years (mean, 37.7 years; median, 42 years). Fourteen patients were newly diagnosed and three were recurrent. The tumors were located in vulva (58.8 %), vagina (23.5 %), buttock (11.8 %), and cervix (5.9 %). The tumors size were 2 to 15 cm in greatest dimension (mean 8 ± 4.4 cm, median 6 cm). Follow-up data was available for nine patients, which ranged from 25 to 124 months (mean, 82 months; median, 80 months). At the end of follow-up, no other recurrence or metastasis was reported. Immunohistochemical analysis showed immunoreactive for estrogen (10/11) and progesterone (8/11) receptor, desmin (6/8), smooth muscle actin (4/10), and vimentin (4/4), S-100 (1/8) and CD34 (1/7). The Ki67 level was less than 5 % in five cases. ConclusionsAAM is a hormone-sensitive, distinct rare mesenchymal neoplasm with high incidence of local recurrence. Surgery is the preferred treatment, with complete resection being an essential prerequisite for minimizing the risk of recurrence.

MED15::TFE3 fusion renal cell carcinoma with extensive cystic change: A clinicopathologic and molecular genetic study of 2 cases, with an emphasis on differential diagnosis.

TFE3-rearranged renal cell carcinomas (RCCs) harbor gene fusions between TFE3 and 1 of many partner genes. MED15::TFE3 fusion RCC is rare, often cystic, and easily misdiagnosed. This study aimed to characterize 2 cases of MED15::TFE3 fusion RCC with extensive cystic change using fluorescence in situ hybridization and targeted RNA sequencing. Both patients were young adult women aged 29 and 35 years. Radiologically, both presented with a cystic Bosniak category II renal lesion. The cysts measured 9.3 cm and 4.8 cm in greatest dimension. Both patients underwent cyst enucleation, and neither had tumor recurrence or metastasis at 26 and 6 months of follow-up, respectively. Microscopically, both tumors were entirely cystic, with thick, fibrous cystic walls lined by small clusters of cells with clear to eosinophilic cytoplasm and uniform, round nuclei with inconspicuous nucleoli. There were also small aggregations of similar clear cells within the cystic walls. Foci of basement membrane-like material depositions were noted in 1 case; calcifications were observed in both cases. Both cases demonstrated nuclear positivity for PAX8 and TFE3 and cytoplasmic staining for Melan-A; HMB45, CAIX, and CK7 were negative. Fluorescence in situ hybridization revealed that both tumors were positive for TFE3 rearrangements. RNA sequencing identified MED15::TFE3 gene fusions in both cases. The main differential diagnosis of MED15::TFE3 fusion RCC includes multilocular cystic renal neoplasm of low malignant potential and atypical renal cysts. Molecular confirmation of TFE3 fusion is essential for establishing the correct diagnosis.

Assessment of CT-KUB as A Diagnostic Tool for Renal Stone Assessment in the Pediatric Population

Introduction Pakistan possesses a larger stone burden in paediatric patients. In the paediatric population, proper and timely diagnosis of renal stones to get the best stone-free rates is essential. This study aims to assess CT-KUB as a diagnostic tool for renal stones in the paediatric population before PCNL. Methodology This is a retrospective, cross-sectional study. Patients between 1 – 15 years with a diagnosis of renal stones were included in the study. Radiological investigations including Ultrasound KUB, X-ray KUB, and before the procedure, CT-KUB were documented. Pre-operative, per-operative, and postoperative complications are used to assess the success of the procedure. The statistical package of Social Sciences 22 was used to enter, sort, and analyze the data. Variables were analyzed in mean ± standard deviation and frequency and percentages. The chi-square test was used to assess the significance of mean differences keeping the p-value as ≤ 0.05. Results The mean age was 4.7 ± 3.8 years with a range of 1 -14 years. After the procedure, 104 (86.6%) were rendered stone-free after the first setting. Only 1 (0.8%) was converted to an open case (Pyelolithotomy). The mean stone size encountered was 1.3 ± 0.7 cm in greatest dimension as measured on the CT scan. Postoperatively, there was a hemoglobin drop of 2.3 ± 0.5 g/dl noted, mean operative time was 94.8 ± 17.4 minutes. Conclusion CT KUB proves to be an important and accurate preoperative diagnostic tool in assessing patients with renal stones in the paediatric population.

Unusual Cause of Small bowel Intussusception

Abstract Introduction/Objective Intussusception is uncommon in adults. When it occurs it is usually secondary to a mass lesion. The purpose of this report is to highlight an unusual cause of intussusception. Methods/Case Report A 48-year-old female presented with right lower abdominal pain, nausea, vomiting, and bloating. She didn’t have a bowel movement in 3-4 days. CT of the abdomen and pelvis demonstrated long segment small bowel intussusception in the right abdomen with a lead point mass. The patient subsequently underwent surgical resection. Grossly the specimen consisted of a 30cm segment of small bowel remarkable for two mucosal nodules measuring 1.9 cm and 1.0 cm in greatest dimension. Microscopically the nodules were composed of sheets of discohesive epithelioid cells with marked nuclear pleomorphism and prominent nucleoli, underlying the normal mucosa. Immunohistochemical studies revealed that the tumor cells to be positive for SOX-10 and MART-1and negative for pan-cytokeratin and DOG1. Diagnosis of malignant melanoma was rendered. Results (if a Case Study enter NA) NA Conclusion Intussusception due to malignant / metastatic melanoma is rare but should be on the differential for patients with symptoms of small bowel obstruction and intussusception with a lead point mass.

Microcystic Stromal Tumor of ovary; Report of a rare entity

Abstract Introduction/Objective Microcystic stromal tumor (MCST) of the ovary is an extremely rare subtype of sex cord- stromal neoplasm first described by Irving and Young in 2009. MSCT is characterized by morphology with microcyst structure, solid cellular areas, and hyalinized fibrous stroma. The most reported tumors were stage I with good prognosis. Methods/Case Report We report a rare case of a microcystic stromal tumor of right ovary in a postmenopausal woman, measuring 25 cm in greatest dimension. The present patient underwent right ovarian tumor resection. Gross examination showed that the tumor was solid and cystic. Immunohistochemically, the tumor expressed CD10, WT1, cyclin D1 and vimentin, and nuclear immunoreactivity for β-catenin but negative for α-inhibin, calretinin, CK AE1/AE3, PLAP, SALL-4, CK7, P53, EMA, CD99, AFP, desmin, CgA, E-cadherin, and melanA. Next Generation Sequencing (NGS) showed rare, pathogenic, gain of function mutation CTNNB1 pT41I. The patient is free of disease at 1-year follow up. Results (if a Case Study enter NA) NA Conclusion MCST is a rare stromal tumor of the ovary. These tumors are considered benign neoplasms because almost all cases display unilateral, localized lesions and have benign outcomes, except for one recurrent case with familial adenomatous polyposis and another initial metastatic case with a CTNNB1 mutation (Zhang Y et al. Hum Pathol 2018, 78:171). MCST is histologically characterized by a microcystic growth pattern, solid cellular areas, and intervening hyalinized stroma, accompanied by immunohistochemical evidence of sex cord-stromal differentiation. Accumulation of nuclear -catenin was reported to be relevant to the pathogenesis of MCST (Maeda D et al. Am J Surg Pathol 2011, 35:1429). More specifically, Maeda et al. observed two cases of ovarian MCST that exhibited a CTNNB1 point mutation in exon 3 and strong nuclear immunoreactivity for -catenin. Other cases exhibited alterations of APC, which is associated with familial adenomatous polyposis (Lee SH et al. Genes Chromosomes Cancer 2015, 54: 353). MCST pathogenesis is linked to -catenin stabilization involving -catenin/Wnt signaling. In our case we found a rare pathogenic, gain of function CTNNB1 T41I c.122C>T mutation which maps within a Gsk3b phosphorylation site of the Ctnnb1 protein (UniProt.org). T41I is predicted to confer a gain of function to Ctnnb1 as demonstrated by nuclear accumulation of Ctnnb1 (Garcia-Rostan G et al. Cancer Res 1999, 59:1811). Our case further expands the histopathologic and molecular spectrum of this rare entity.

DICER1-Mutant Thyroid Carcinoma of Unusual Morphology: A Follicular Carcinoma with Bizarre Nuclei or a Novel Entity?

Abstract Introduction/Objective DICER1 mutations are associated with a host of benign and malignant neoplasms, of which the thyroid ranks among those with the highest prevalence. We present a case of a DICER1-mutant thyroid carcinoma with unusual morphologic features not described in the existing literature. Methods/Case Report A 29-year old 33 weeks pregnant female presented with swelling of the left neck. The patient subsequently underwent an ultrasound, which revealed a thyroid lesion measuring 6.2cm in greatest dimension. Labs including TSH and free T4 wree within normal 3rd trimester limits. Following an unremarkable delivery, FNA revealed loosely clustered cells with marked hyperchromasia and nuclear pleomorphism and variable microfollicular architecture in a colloid-containing background. Though definitively malignant, the anomalous cytomorphology of this neoplasm prompted molecular testing by Afirma Genomic Sequencing Classifier and Xpression Atlas next-generation sequencing, which was significant for a DICER1 hotspot mutation (p.E1705K c.5113G>A). Follow-up total thyroidectomy was pertinent for a tan-red, nodular mass involving 95% of the thyroid. Histomorphology revealed a neoplasm of primarily macrofollicular architecture with scattered microfollicles and intervening zones that appeared poorly-to-undifferentiated. Cells demonstrated bizarre hyperchromatic, pleomorphic nuclei with multinucleation and Azzopardi effect. Capsular invasion was identified. Inconsistent with a poorly-differentiated or anaplastic carcinoma, the mitotic rate and Ki-67 index were low at < 1/2mm2 and 1-2%, respectively. The tumor was consequently theorized to represent a follicular carcinoma with bizarre nuclei or other entity associated with DICER1 mutations not previously described. To date, no recurrence or metastasis has occurred. Results (if a Case Study enter NA) NA Conclusion We report an enigmatic morphology of a thyroid cancer associated with a DICER1 mutation. DICER1 mutations have been hitherto described in follicular carcinoma, papillary carcinoma, poorly-differentiated carcinoma and thyroblastoma, none of which are consistent with the present case. Thus, we conjecture that this morphomolecular profile may constitute a "follicular carcinoma with bizarre nuclei" or other novel entity not previously reported. Further investigation should be pursued to determine the nature of this entity, its pathophysiology, epidemiology, possible association with germline DICER1 syndrome, and relationship between morphology and prognosis in patients with DICER1 mutations.

A Skin Inflammatory Myofibroblastic Tumor Penetrates Through Skull To The Dura: A Case Report

Abstract Introduction/Objective Inflammatory myofibroblastic tumor (IMT) is currently accepted to be a true neoplasm with a wide spectrum of biological behavior, varying from benign lesions to the rare tumors which are multifocal and prone to recurrence. IMT is characterized by a proliferation of myofibroblastic spindle cells with an inflammatory infiltrate. It was first described in the lung and later on reported in various sites such as stomach, intestine, spleen, bone. Here we report a rare IMT case in that the tumor penetrates through skull and extends to the dura. Methods/Case Report A 29-year-old female presented with a slowly progressive upper head scalp mass of one-year duration. Magnetic resonance imaging showed a soft tissue mass that extended through the skull and into the dura. Patient denies headache, syncopal episodes, neck pain, back pain, radicular symptoms, weakness, ataxia, nausea, vomiting, bladder or bowel incontinence, saddle anesthesia, or changes from baseline hearing, vision, or speech. Grossly, serial sectioning of the scalp skin specimen revealed a well-circumscribed mass lesion with white, firm, and homogeneous cut surface, with no hemorrhage or necrosis identified. The lesion measured 7.0 x 6.5 x 1.7 cm in greatest dimension. The lesion involved the deep margin and extended to the skull and dura. On histopathological examination, the lesion was composed of variable admixture of spindle cells with eosinophilic cytoplasm and inflammatory cells comprising of plasma cells and lymphocytes. The spindle cells were positive for smooth muscle actin, CD10 (partial), and negative for AE1/AE3, ALK–1, CD34, CD68, CD117, Desmin, Myogenin, p53, S-100, and SOX-10. The Ki-67 showed a spindle cell proliferation index at about 2%. The patient successfully went through surgery and was followed up without complications. Results (if a Case Study enter NA) NA Conclusion Our case showed a rare IMT case harboring histologically benign features like low cellularity, minimal nuclear atypia, and low proliferative index, but demonstrating locally very aggressive biological behaviors. Complete surgical resection and close follow up are suggested to avoid recurrence. Further studies are needed in this field to design in-depth investigation for accurate diagnosis and better clinical outcomes.

SAT563 Follicular Thyroid Cancer Masquerading as Chest Wall Mass With an Aggressive Course

Abstract Disclosure: I. Goyal: None. E. Punni: None. L. Adhikari: None. Introduction:Follicular thyroid cancers (FTC) are more aggressive than papillary thyroid cancer and usually have more advanced tumor stage at the time of presentation. Musculoskeletal metastases are rare though, but when present can cause various complications like pathological fractures and nerve compression. Clinical case:A 75-year-old female was seen in orthopedics clinic for a left infraclavicular chest wall mass. MRI chest showed a large destructive mass invading the manubrium. Biopsy showed follicular cells consistent with ectopic thyroid tissue. CT neck/chest showed 2x1.8 cm right thyroid lobe nodule and left sternoclavicular joint metastasis. She underwent total thyroidectomy and resection of portions of manubrium, left clavicle and left 1st and 2nd rib. Pathology showed FTC in right thyroid lobe, measuring 2.6 cm in greatest dimension with angioinvasion, and FTC of manubrium, adjacent connective tissue and sternoclavicular joint and ribs, measuring 6.3 cm in greatest dimension. Pathological TNM staging was pT2N0M1. Her 6-week post-op thyroglobulin (Tg) level was 28.7 ng/mL (Beckman Coulter Immunometric Assay, reference value <0.1 athyrotic). She was started on levothyroxine supplementation to achieve a TSH <0.01 uIu/mL. She was subsequently treated with 200 mCi of radio-active iodine (RAI) as adjuvant therapy. Post-therapy whole body scan showed increased activity in the right strap muscle and iodine-avid osseous metastasis in right hemisacrum. She further received radiation therapy to neck and sternal regions, and the right sacroiliac joint. Following this, patient was monitored with serial Tg panel and neck ultrasound (US). Her initial post-op US neck showed a soft tissue fullness in right thyroidectomy bed, concerning for residual disease but this was no longer seen after 3 months. Her Tg level downtrended from 28.7 ng/mL to 12.6 ng/mL and further to 1.8 ng/mL at 1-year follow-up. However, her course was complicated by development of several oral ulcers resulting from high-dose RAI therapy which were treated symptomatically with hydration, topical analgesics and Listerine mouth washes. The patient reported ongoing bowel incontinence since her initial cancer diagnosis. MRI pelvis showed rim-enhancing 4.5cm lesion centered at right sacral ala and extending into adjacent S1/S2 neural foramina. She was re-referred for palliative radiation therapy.Conclusion:This case of FTC is unique due to its uncommon initial presentation. Skeletal metastases to sacrum resulted in bowel incontinence in our patient. When present, skeletal metastases need treatment with high-dose (200 mCi) RAI. RAI therapy can cause xerostomia, hypogeusia and sialadenitis due to reductions in salivary flow. Clinicians should be aware of the early and late-onset complications of RAI therapy, discuss these with the patient before therapy and manage the complications adequately if these occur. Presentation Date: Saturday, June 17, 2023

FRI220 Primary Bilateral Macronodular Adrenal Hyperplasia: A Rare Cause Of Cushing Syndrome

Abstract Disclosure: Y. Ortiz: None. A.M. Aviles Melendez: None. M.M. Mangual Garcia: None. J.M. Garcia-Mateo: None. Primary bilateral macronodular adrenal hyperplasia (PBMAH) is a highly heterogenous entity whose pathophysiology remains largely unclear, representing less than 2% of Cushing syndrome (CS) cases, which leads to a challenging diagnosis. Many patients have a mild clinical picture and remain undiagnosed until abdominal imaging for unrelated reasons reveals bilateral adrenal enlargement. Hereby, we describe the case of a patient presented with abdominal pain and clinical hypercortisolism due to PBMAH. Case of a 42-year-old female with past medical history of arterial hypertension, referred for evaluation due to bilateral adrenal masses found on abdominal CT scan performed after patient presented with abdominal discomfort. On initial evaluation, patient refers a 50 pounds weight gain, increase in abdominal circumference, muscle weakness and sudden onset of facial and abdominal hair growth. Physical examination reveals dorsocervical fat pad, proximal muscle weakness, moon facies, facial and abdominal hirsutism. Abdominal CT scan with adrenal protocol showed bilateral adrenal lesions, with largest measuring 2.8 and 3.9 cm on the left side, with attenuation of 16 and 7.4 Hounsfield units. The absolute and relative washouts for the first were 76.6% and 61.6%, and for the second 73.5% and 67.1%, both consistent with adenomas. Laboratory results showed late night salivary cortisol levels of 4.60 ug/dl and 4.80 ug/dl, values which may be high or even normal due to ineffective steroidogenesis on PBMAH. Other labs consisted of low dose 1 mg dexamethasone suppression test: 4.80 ug/dl, and ACTH level: 9.60 pg/ml, which confirms clinical hypercortisolism, indeterminate for ACTH-independent cause. Desmopressin test was not performed, since levels may not be fully suppressed in PBMAH due to ectopic production by adrenal glands, leading to an erroneous diagnosis of ACTH-dependent CS. DHEA level of 618 ug/dl can also be increased, which could lead to a diagnosis of adrenocortical carcinoma. Considering risk of recurrence, risk for adrenal insufficiency, and lower documented complications, unilateral left-sided adrenalectomy was chosen as the best surgical treatment, despite bilateral adrenalectomy being the gold standard for diagnosis. Surgical pathology report showed Adrenocortical adenoma with associated myelolipomatous foci of 7.5 cm in greatest dimension. Despite limited data regarding unilateral adrenalectomy, it appears to convey clinical and biochemical benefits in most cases. Initial remission reported reaches more than 90% with low risk of recurrence between 10-15%. Adrenal insufficiency, despite the presence of residual hyperplastic adrenal tissue, occurs in about one-third of patients and is usually transient. Our case is a great example of the importance of individualization of management options based on therapy benefits, and decreased risks of future complications. Presentation: Friday, June 16, 2023

Novel EWSR1::GFI1B gene fusion in angiofibroma of soft tissue.

Angiofibroma of soft tissue is a benign soft tissue tumour characterised by bland spindle cells and a distinct branching vascular network. The majority of soft tissue angiofibromas harbour AHRR::NCOA2 gene fusions. Here we present three cases of EWSR1::GFI1B-fused soft tissue tumours that are morphologically most reminiscent of soft tissue angiofibroma. All three cases presented in male patients with an age range of 35-78 years (median = 54 years). Two cases presented as subcutaneous nodules on the trunk (posterior neck and chest wall); one was an intramuscular foot mass. The tumours were unencapsulated nodules with infiltrative margins ranging from 2.2 to 3.4 cm in greatest dimension. Histologically, the tumours contained uniformly bland fibroblastic spindle cells with ovoid to fusiform nuclei and delicate cytoplasmic processes embedded in a myxoid to myxocollagenous stroma. All three cases were characterised by a thin-walled, branching vascular network evenly distributed throughout the tumour. Overt cytological atypia or conspicuous mitotic activity was absent. The spindle cells had an essentially null immunophenotype. By targeted RNA sequencing, an in-frame gene fusion between EWSR1 exons 1-7 and GFI1B exons 6-11 or 7-11 was detected in all three cases. The tumours were marginally excised. For all three cases, there were no documented local recurrence or distant metastases during a limited follow-up period of 6-10 months. We propose that EWSR1::GFI1B may represent a novel fusion variant of soft tissue angiofibroma.

Untying the Gordian knot of composite hemangioendothelioma: Discovery of novel fusions.

Composite hemangioendothelioma is a rare, locally aggressive, and rarely metastasizing vascular neoplasm which affects both children and adults. Recently, a number of gene fusions including YAP1::MAML2, PTBP1::MAML2, and EPC1::PHC2 have been detected in a small subset of cases with or without neuroendocrine expression. Herein, we present four additional cases with novel in-frame fusions. The cohort comprises two females and two males with a wide age range at diagnosis (24-80 years). Two tumors were deep involving the right brachial plexus and mediastinum, while the remaining were superficial (right plantar foot and abdominal wall). The size ranged from 1.5 to 4.8 cm in greatest dimension. Morphologically, all tumors had an admixture of at least two architectural patterns including retiform hemangioendothelioma, hemangioma, epithelioid hemangioendothelioma, or angiosarcoma. The tumors were positive for endothelial markers CD31 (3/3), ERG (4/4), and D2-40 (1/4, focal), while SMA was expressed in 2/3 highlighting the surrounding pericytes. Synaptophysin showed immunoreactivity in 2/3 cases. One patient had a local recurrence after 40 months, while two patients had no evidence of disease 4 months post-resection. Targeted RNA sequencing detected novel in-frame fusions in each of the cases: HSPG2::FGFR1, YAP1::FOXR1, ACTB::MAML2, and ARID1B::MAML2. The two cases with neuroendocrine expression occurred as superficial lesions and harbored YAP1::FOXR1 and ARID1B::MAML2 fusions. Our study expands on the molecular spectrum of this enigmatic tumor, further enhancing our current understanding of the disease.

Malignant gastrointestinal neuroectodermal tumor: a clinicopathological analysis of three cases

Objective: To investigate the clinicopathological characteristics of malignant gastrointestinal neuroectodermal tumors (GNET), and to describe their clinical, histological, immunophenotypic, ultrastructural, and molecular features, diagnosis and differential diagnosis. Methods: Three cases of malignant GNET were collected at Xijing Hospital of the Fourth Military Medical University, from 2013 to 2022. All patients underwent surgical resection of the tumor. Histological, immunohistochemical (IHC), ultrastructural and molecular genetic analyses were performed, and the patients were followed up for six months, three years and five years. Results: There were two males and one female patients. The tumors were located in the ileum, descending colon, and rectum, respectively. Grossly, the tumors were solid, firm, and poorly circumscribed, measured in size from 2 to 4 cm in greatest dimension, and had a greyish-white cut surface. These tumors were histologically characterized by a sheet-like or nested population of oval to spindled cells or epithelioid cells with weakly eosinophilic or clear cytoplasm, small nucleoli and scattered mitoses. Electron microscopy showed neuroendocrine differentiation, and no evidence of melanogenesis. IHC staining showed that the tumor cells were diffusely positive for S-100 protein, SOX10, CD56, synaptophysin and vimentin. They were negative for melanocytic markers, HMB45 and Melan A. All three cases showed split EWSR1 signals consistent with a chromosomal translocation involving EWSR1. Next-generation sequencing in one case confirmed the presence of EWSR1-ATF1 fusion. These patients were followed up for 6 months, 3 years and 5 years, respectively, and all of them developed possible lung or liver metastases, and one of them died of multiple pulmonary metastases. Conclusion: Malignant GNET has distinctive morphological, IHC, and molecular genetic features and it should be differentiated from other malignancies of the gastrointestinal tract, especially clear cell sarcoma and melanoma.

Metaplastic breast carcinoma: Analysis of clinical and pathologic features, a five-year study.

Metaplastic carcinoma breast (MCB) is a rare tumor comprising of both glandular and non-glandular patterns with epithelial and or mesenchymal components. Due to their varied clinicomorphological features, diagnosis has been challenging. To study the clinicopathological and histomorphology of cases of metaplastic carcinoma breast diagnosed in a tertiary care hospital along with literature review. This is a retrospective study including data of 11 patients who were diagnosed with MCB either on trucut or mastectomy specimens conducted between January 2014 and December 2018. The study includes 11 patients, out of which 10 were diagnosed on mastectomy while one on trucut specimen. All the patients were women with the mean age of presentation being 43.8 years. The most common presentation was palpable breast lump with mean tumor size of 7.3 cm in greatest dimension. Skin involvement was seen in 36.3% of cases. While eight cases (72.7%) were classified as epithelial, three (27.2%) were classified as mixed. Amongst epithelial variety, in eight cases, squamous component was seen along with infiltrating ductal carcinoma (IDC) while one was pure squamous type. In mixed variety, one case showed spindled areas along with squamous areas and areas of IDC. Other two showed focal sarcomatous and cartilaginous areas in one and angiosarcomatous, bone and cartilage formation admixed with areas of IDC in other case. MCB are rare breast tumors with aggressive course and are characterized by their large size and rapid growth rate. Recently, there has been an upsurge in the cases of MCB due to increase in recognition of this entity. It has to be distinguished from other tumors by the pathologists so as to guide proper treatment.

Inhibin-Positive "Cholangioblastic" Variant of Intrahepatic Cholangiocarcinoma: Report of 3 New Patients With Review of the Literature.

Cholangiocarcinoma is the second most common primary liver malignant neoplasm. It usually affects older individuals in their seventh decade of life with no gender predilection. Recently, a distinct subtype of cholangiocarcinoma has emerged with 2 proposed names: "cholangioblastic" and "solid tubulocystic." This variant predominantly occurs in younger women who lack the common risk factors for patients diagnosed with cholangiocarcinomas, such as older age and chronic liver disease or cirrhosis. We describe 3 new patients with a cholangioblastic variant of intrahepatic cholangiocarcinoma. At the time of diagnosis, the patients were aged 19-, 46-, and 28-year-old; 2 females and 1 male (the 46-year-old). None of our patients had a history of chronic liver disease or known predisposing factors for liver tumors. Tumor size ranged from 2.3 to 23 cm in greatest dimension. Histological examination of these tumors demonstrated reproducible morphology characterized by trabecular, nested, and multicystic patterns with micro and macro follicles filled with eosinophilic material. The immunohistochemical profile showed that the tumor cells were positive for keratin 7, inhibin, synaptophysin, and albumin in situ hybridization, while negative for HepPar1, arginase, and INSM1. All tumors lacked conventional intrahepatic cholangiocarcinoma/adenocarcinoma morphology. We also review the literature and emphasize that neuroendocrine tumors should be recognized as a major diagnostic pitfall of this variant.