Rare Subtype Research Articles

Leiomyoma with bizarre nuclei occurring post hysterectomy mimicking malignancy: a rare case report

Abstract Introduction/Objective Leiomyoma with bizarre nuclei (LBN), also known as symplastic leiomyoma, represents a rare subtype of benign uterine smooth muscle neoplasm. Histologically, it is characterized by significant cytological atypia in a typical leiomyoma background with rare mitoses and without tumor necrosis. Methods/Case Report We report a case of a 48-year-old woman, status post hysterectomy for symptomatic fibroids, with imaging showing multiple contiguous pelvic masses extending from the pelvis to the upper abdomen and displacing the colon laterally and small bowel posteriorly. The findings were highly suspicious for ovarian malignancy. A bilateral salpingo-oophorectomy and a partial colectomy were performed with tumor debulking and omentectomy. Grossly, multiple well-circumscribed soft masses ranging in size from 1.5-16 cm, in contiguity with pericolonic mesentery with a smooth fleshy cut surface and cystic changes were found. Bilateral ovaries were unremarkable. Microscopically the larger masses were composed of spindle cells with bizarre nuclei throughout, while smaller masses showed foci of bizarrely shaped-spindle cells with bizarre nuclei in a background of a typical leiomyoma. Mono- and multinucleated cells with smudged chromatin were also seen. The mitotic index was low confirmed with a low Ki-67 proliferation index (< 5%). Immunohistochemical stainings showed that the neoplastic cells were positive for desmin, SMA, and caldesmon; and negative for CD10, with a wild type p53 expression. Fumarate hydratase immunostain was retained. MDM2 amplification was not detected by FISH. The morphology and immunohistochemical findings were compatible with LBN. Results (if a Case Study enter NA) NA Conclusion In summary, this is a rare and challenging case of multiple LBN developed years post hysterectomy and clinically mimicking a malignancy.

EVERY KERATIN-POSITIVE MALIGNANT TUMOR IN THE ADRENAL GLAND IS NOT METASTATIC CARCINOMA- A CASE REPORT

Abstract Introduction/Objective Angiosarcoma is a rare subtype of sarcoma arising from the vascular endothelial cells. Primary adrenal angiosarcoma (PAA) is an exceedingly rare entity, with only 53 cases documented in the literature so far. Methods/Case Report A 78-year-old female presented with left upper quadrant abdominal pain and early satiety. A computed tomography scan of the abdomen revealed a 15 x 13 x 16 cm, heterogeneous enhancing mass with interspersed calcifications, possibly originating from the left adrenal gland. The mass was found to be displacing the spleen and the left kidney. An ultrasound-guided biopsy of the mass was inconclusive, and the patient subsequently underwent resection of the left retroperitoneal mass, left adrenalectomy, splenectomy, and left partial nephrectomy. Gross examination revealed a slightly ruptured, red-brown mass (19.5 x 12.7 x 12.6 cm, 1784g), which was serially sectioned to reveal diffusely hemorrhagic and necrotic cut surfaces. On microscopic examination, the tumor was almost entirely hemorrhagic and necrotic, with a few viable areas that were composed of solid sheets of markedly pleomorphic epithelioid cells with a high nuclear-cytoplasmic ratio, prominent nucleoli, and increased mitotic figures. There were also a few ectatic vascular spaces lined by these markedly pleomorphic epithelioid cells. Immunohistochemical stains of the tumor cells showed positive results for cytokeratins, CD31, ERG, and friend leukemic integration 1 (FLI-1), while Inhibin and SF-1 were negative. A diagnosis of epithelioid angiosarcoma was rendered. Results (if a Case Study enter NA) NA Conclusion PAA can be difficult to diagnose since it is rare, and thus it is not typically considered in the initial differential diagnosis. Most PAA have an epithelioid morphology, and they frequently test positive for cytokeratins. Biopsy diagnosis can also be challenging, as the mass may exhibit extensive necrosis and hemorrhage. Considering its rarity, large adrenal masses with heterogeneous features on imaging PAA should be considered as a differential diagnosis.

Ovarian Microcystic Stromal Tumor with Significant Nestin Expression: A Unique Case.

Ovary microcystic stromal tumor (MCST) is an extremely rare subtype of sex cord-stromal neoplasm, and only 57 cases have been reported. We herein report a unique case of ovarian MCST with positive nestin expression in a 39-year-old Chinese woman. The tumor showed microcystic stromal histological structures and characteristically expressed the CD10, WT-1, and Ki67 proteins. A molecular analysis identified a point mutation (c.110C > T) in exon 3 of the CTNNB1 gene. To our knowledge, no report has described a case of ovarian MCST with positive staining for nestin protein. Our study provides new insights into the tumor biology of ovarian MCST.

A discussion of pediatric therapy-related acute myeloid leukemia with a rare t(8;16) translocation

Abstract Introduction/Objective Secondary acute myeloid leukemia is a type of blood cancer that arises after a previous myeloid neoplasm or after exposure to chemotherapy. Certain genetic mutations and chromosomal abnormalities can occur as a result of said cytotoxic drug-related effects. Here, we discuss a case of secondary acute myeloid leukemia with a rare translocation following hemophagocytic lymphohistiocytosis Etoposide treatment in a 13-year-old female. After less than a year into her initial treatment, the patient presented to the emergency department with severe bone pain. A full hematologic workup was performed, including bone marrow biopsy, flow cytometry analysis, and subsequent genetic studies. A diagnosis of therapy-related acute myeloid leukemia was made. Genetic studies revealed a rare t(8;16) translocation which presents with a unique morphology and prognosis that will be discussed here. Methods/Case Report A 13-year-old female presented to the emergency department for evaluation of fever, myalgia, and swelling in her clavicle. The patient’s history was notable for hemophagocytic lymphohistiocytosis with subsequent Etoposide chemotherapy treatment which she received less than a year prior to her visit. CBC was notable for low white blood cell count, low hemoglobin, increased neutrophilic bands, and decreased lymphocytes. Given her past medical history and worsening pain without a clear reason, hematology was consulted. Results (if a Case Study enter NA) A blast count of 61.8% was reported via flow cytometry with the cells seen in the dim CD45+, moderate to bright side-scatter region, co-expressing CD4, CD14 (dim, heterogeneous), CD15, CD16 (dim), CD64, HLA-DR, and MPO. The bone marrow biopsy was described as hypercellular with the predominant cell type as blasts at 66.4%. Numerous hemophagocytic blasts were noted as well. Acute leukemia next generation sequencing panel revealed a t(8;16)(p11;p13.3) KATA6A::CREBBP fusion without other abnormalities in the evaluated genes. This workup as a whole rendered the diagnosis of acute myeloid leukemia with KAT6A::CREBBP. Conclusion Diagnosing acute myeloid leukemia with KATA6A::CREBBP is important for prognostic factors. Knowing the patient’s history regarding her prior chemotherapy with Etoposide is also imperative for distinguishing a de novo presentation of this rare subtype, versus a therapy-related myeloid neoplasm. The patient was started on chemotherapy for her acute myeloid leukemia shortly thereafter the diagnosis.

Invasive Micropapillary Carcinoma of the Breast: Comparison of Clinical, Epidemiological, Anatomopathological and Therapeutic Features with Infiltrating Carcinoma of Non-Specific Type

Invasive micropapillary carcinoma (IMCC) is a rare histological subtype of invasive breast cancer, its frequency ranges from 1.0 to 8.4% of all breast cancer cases. It is identified as a particularly aggressive tumor since frequent invasion of vessels, skin and lymph nodes is often reported. The aim of the work is to describe and compare the epidemiological, clinical, anatomopathological and molecular aspects of CMPI compared to CINS. Compare the overall survival of the two groups in order to identify the prognostic factors for CMPI. This is a retrospective, descriptive and analytical study spread over 6 years from January 2015 to December 2020, involving all cases of CMPI and CINS of the breast collected at the Obstetrics and Gynecology department of the Maternity and Neonatology Center of Monastir. The frequency found was 5.5% for CMPI and 72.69% for CINS. In our series we found the average age to be more advanced in CINS compared to CMPI without having a statistically significant difference (p=0.49). CMPI tends to be slightly larger than CINS with an average size of 3.7 compared to 3 for CINS. The right breast was the predominant tumor site for the 2 types of cancer p=0.71. CMPI presents a higher frequency of locoregional ADP and vascular emboli with p=0.001. Distant metastases were more frequent in CINS but without having a statistically significant difference. The overall survival of CMPI is 76% versus 86.4%. % of CINS. CMPI represents a particular variety of breast carcinomas; in this study we tried to dissect its different epidemiological, clinical, radiological and therapeutic characteristics which were largely in agreement with the literature.

Primary Squamous Cell Carcinoma of the Breast With 18 F-FDG PET/CT.

A 67-year-old woman presented with a palpable breast mass. A biopsy was taken, and the diagnosis was squamous cell carcinoma. Primary squamous cell carcinoma of breast is an extremely rare subtype of invasive breast cancer. The diagnosis requires ruling out metastasis of other sites and that is not skin origin. The patient was referred to 18 F-FDG PET/CT for diagnosis and staging. In this report, we present PET/CT and postsurgical pathology findings.

A case report: mucinous carcinoma of extrahepatic bile ducts with periportal calcification suggestive of lymphatic calcification.

Mucinous carcinoma is a rare subtype of extrahepatic bile duct (EHBD) cancer in which abundant mucin surrounds cancer cell nests. Calcification is often observed in mucus-producing tumors, and we herein report a case of mucinous carcinoma of EHBD with diffuse periportal calcifications. A 92-year-old woman was seen for jaundice. Non-contrast CT showed diffuse semi-linear branching calcifications extending from the hepatoduodenal ligament along the long axis of the intra- and extrahepatic portal veins. A bile duct mass and multiple lymph nodes were hyperintense on T2-weighted MRI images, and periportal abnormal intensity was visible along the intrahepatic portal tract. On contrast-enhanced CT, the mass and enlarged lymph nodes showed a weak enhancing effect. In addition, a lesion with a similar enhancing effect was observed in parallel with periportal calcification, raising suspicion of tumor extension. An endoscopic bile duct biopsy was performed, which resulted in the tumor being diagnosed as a mucinous carcinoma. Considering the imaging findings, it was determined to be a mucinous carcinoma of EHBD origin, with lymphatic vessel infiltration and multiple lymph node metastases. The lymphatic tracts presented lymphangitic carcinomatosis extending from the hepatoduodenal ligament to intrahepatic portal tracts, and the diffuse periportal calcification was presumed to be calcification associated with the mucin component of tumor infiltration.

High-Throughput Transcriptomics Identifies Chemoresistance-Associated Gene Expression Signatures in Human Angiosarcoma

Angiosarcomas, clinically aggressive cancers of endothelial origin, are a rare subtype of soft-tissue sarcomas characterized by resistance to chemotherapy and dismal prognosis. In this study, we aim to identify the transcriptomic biomarkers of chemoresistance in angiosarcoma. We examined 72 cases of Asian angiosarcomas, including 35 cases treated with palliative chemotherapy, integrating information from NanoString gene expression profiling, whole transcriptome profiling (RNA-seq), immunohistochemistry, cell line assays, and clinicopathological data. In the chemoresistant cohort (defined as stable disease or progression), we observed the significant overexpression of genes, including SPP1 (log2foldchange 3.49, adj. p = 0.0112), CXCL13, CD48, and CLEC5A, accompanied by the significant enrichment of myeloid compartment and cytokine and chemokine signaling pathways, as well as neutrophils and macrophages. RNA-seq data revealed higher SPP1 expression (p = 0.0008) in tumor tissues over adjacent normal compartments. Immunohistochemistry showed a significant moderate positive correlation between SPP1 protein and gene expression (r = 0.7016; p < 0.00110), while higher SPP1 protein expression correlated with lower chemotherapeutic sensitivity in patient-derived angiosarcoma cell lines MOLAS and ISOHAS. In addition, SPP1 mRNA overexpression positively correlated with epithelioid histology (p = 0.007), higher tumor grade (p = 0.0023), non-head and neck location (p = 0.0576), and poorer overall survival outcomes (HR 1.84, 95% CI 1.07–3.18, p = 0.0288). There was no association with tumor mutational burden, tumor inflammation signature, the presence of human herpesvirus-7, ultraviolet exposure signature, and metastatic state at diagnosis. In conclusion, SPP1 overexpression may be a biomarker of chemoresistance and poor prognosis in angiosarcoma. Further investigation is needed to uncover the precise roles and underlying mechanisms of SPP1.

The utility of PET-CT in baseline and sequential characterisation of Pulmonary Pleomorphic Carcinoma

Pulmonary Pleomorphic Carcinomas (PPCs) represent a rare and aggressive subtype of Non-Small Cell Lung Cancer (NSCLC) that can only be definitively diagnosed on a surgical specimen. This study utilised PET-CT to evaluate radiological characteristics of PPCs. This study retrospectively evaluated the radiological characteristics of PCCs diagnosed in St James’s Hospital Dublin between 2012-2023. Computed Tomography (CT) and Positron Emission Tomography (FDG-PET) imaging features (size, location, density, shape, invasion, and growth kinetics) and standard uptake value for each lesion were evaluated. 39 PCCs were identified with a mean age of 66.5 years (range: 49-82 years). FDG-PET was performed in all 39 cases. Tumours demonstrated a high FDG uptake at baseline with a mean (SUV) of 12.6 (range: 1.4 - 36.9). A second interval PET-CT on average 3.3 months after the first in 3 cases demonstrated over 120% increase in SUV. The mean tumour size was 4.3 cm (range: 1.0 - 14.5 cm). Tumours developed rapid interval growth, reaching a mean maximum diameter of 6.6 cm (53.4%) within a mean of 2.1 months. Tumours were predominantly located in the upper lobe (71.8 %) and displayed necrotic features in 53.8 % of cases. 82.1% of tumours invaded the mediastinum. This study describes the largest cohort of Pulmonary Pleomorphic Carcinoma in the literature. Tumours demonstrate a high SUV on baseline imaging and demonstrate rapid growth on interval imaging and central necrosis. Please click on the 'PDF' for the full abstract!

A Novel Homozygous Variant in CPLANE1 Gene in a Patient with Developmental Deficits

Background: Oral-facial-digital syndrome (OFDS) type 6 is a rare subtype of Joubert syndrome characterized by orofacial anomalies and polydactyly with neurological features of Joubert syndrome. This rare syndrome is divided into thirteen subtypes, all of which demonstrate autosomal recessive inheritance, except for OFDS type 1 which demonstrates X-linked dominant inheritance. Case Presentation: A 19-year-old man with mild developmental delay was brought to a rural community clinic, as he had become irritable and angry, in the recent past. There was no history of prior medical conditions. In view of orofacial anomalies, and developmental deficits, a genetic analysis was requested. Karyotype analysis revealed a normal male karyotype (46,XY) in all 30 metaphase spreads analyzed. No numerical or structural chromosomal abnormalities were observed. Clinical exome sequencing and chromosomal microarray detected a variant of uncertain significance in exon 5 of CPLANE1 gene c.365T>G (p.Val122Gly) leading to substitution of Glycine for Valine. This was confirmed by Sanger sequencing. Parents were heterozygous, and the unaffected sibling was homozygous for the wild-type allele. This variant has not been reported earlier in the mutation databases or gnomAD. Runs of homozygosity (ROH) analysis showed a 3.2 Mb ROH around the CPLANE1 gene in the proband, which was absent in both parents and the unaffected sibling. Conclusion: We find a novel homozygous mutation in the CPLANE1 gene in a patient of non-consanguineous parentage with atypical orofacial features. This suggests that potentially deleterious, rare variants may occur in the heterozygous state in the population. Hence, sequencing of population samples might help understand the genetic epidemiology of rare syndromes.

"Y appearance" infarction: caused by essential thrombocythemia.

Essential thrombocythemia (ET) is a myeloproliferative malignancy caused by the excessive proliferation of megakaryocytes in the bone marrow, resulting in the overproduction of peripheral platelets. ET can lead to thrombotic events, such as ischemic stroke (IS), though it is a rare cause of IS. Bilateral medial medullary infarction (BMMI), also known as "Y appearance" infarction due to its distinctive imaging morphology, is a rare clinical subtype of IS which typically has a poor prognosis and a high mortality rate. Herein, we report the case of a 43-year-old male with a history of ET. The patient's platelet count was poorly controlled, and he did not receive regular treatment. After developing symptoms such as dizziness, dysphagia, choking on water, slurred speech, blurred vision, and bilateral limb numbness. Head magnetic resonance imaging revealed a "Y appearance" infarction in the bilateral medial medulla. After admission, the patient was administered intravenous antiplatelet therapy with tirofiban. However, when he was switched to oral aspirin after three days, he experienced decreased muscle strength and worsening symptoms. Therefore, tirofiban was continued for 14 days. Upon discharge, the patient experienced residual limb numbness. His National Institutes of Health Stroke Scale score was 1, Modified Rankin Scale score was 0, and platelet count had decreased to the normal range. During the 9-month follow-up period after discharge, the patient still had only mild limb numbness. Our report presents a special case of "Y appearance" infarction due to ET. Owing to fluctuations in the patient's condition, he received long-term high-dose tirofiban, which ultimately led to a significant improvement in his symptoms.

Diagnosis and management of Rosai–Dorfman disease of the breast: Case report and literature review

AbstractRosai–Dorfman disease (RDD) is a rare subtype of non–Langerhans cell histiocytosis. It is a benign disease with variable presentations, with breast involvement being an uncommon manifestation. In this paper, we present a case of breast RDD in a 59‐year‐old Chinese woman who presented with a painless, enlarging mass in her right breast, accompanied by skin changes and no palpable axillary lymph node. A mammogram and breast ultrasonography revealed a progressively enlarging lesion with a suspicious axillary lymph node, leading to an upgrade from Breast Imaging Reporting and Data System (BIRADS) score of 3 to 4A on interval imaging. Core biopsy of the breast mass and cytology of the right axillary lymph node confirmed extranodal RDD. After a 5‐year period of observation, excision was performed due to persistent symptoms. Local recurrence of RDD, with skin discolouration and thickening, was confirmed by skin biopsy 1 year and 9 months after the operation. To the best of our knowledge, this is the first reported case of breast RDD in Hong Kong.

6400 An Unusual Presentation of Silent Corticotroph Pituitary Macroadenoma

Abstract Disclosure: N. Mon: None. V. Lohano: None. B. Williams: None. N. Lehman: None. R. Kulkarni: None. S.L. Mokshagundam: None. Silent Corticotroph Pituitary Adenomas (SCA) are a rare group of nonfunctioning pituitary adenomas (NFA) comprising 3-6% of all pituitary adenomas and up to 20% of corticotroph adenomas. SCA are biologically and clinically distinct from Cushing disease and NFA. SCA present with headache, visual field impairment, hypopituitarism, and pituitary apoplexy. We present a case of SCA with the initial presentation of syncope with undetectable ACTH and very low AM cortisol level.A 67 year-old-female was incidentally found to have a pituitary macroadenoma in MRI brain for syncope work up in 2017. MRI reported 1.4 x 1.2 x 1.3 cm sellar mass with suprasellar extension, minimal mass effect on the optic chiasm and no cavernous sinus invasion. Initial labs showed ACTH <5 (7.2-63.3 pg/mL), AM cortisol 0.8 (6-28ug/dl), Prolactin 101.1 (3.3-27 ng/mL), TSH 0.08 (0.34-5.60 uIU/mL), Free T4 0.6 (0.58-1.64 ng/dL), FSH 1.7 (2-5 mIU/mL), LH <0.2 (1-13 mIU/mL), IGF-1 33 ( 41-279 ng/mL). ACTH stimulation test: cortisol 0.5 ug/dl at baseline, 5.8 ug/dl at 60min. She was diagnosed with panhypopituitarism and hyperprolactinemia due to stalk effect. Hydrocortisone and Levothyroxine (LT4) were started. She underwent pituitary macroadenoma resection for optic chiasm decompression in 2017. Pathology reported pituitary neuroendocrine tumor (pitNET), but no immunostaining was done at that time. Follow up MRI in 2019 showed residual pituitary tumor. In 2023, she endorsed headaches, mood changes, fatigue and weight gain. Physical exam was unremarkable except BMI 34.75. Prolactin, Free T4, IGF-1 were normal. MRI in 2023 revealed recurrent and enlarging pituitary adenoma (1.9 x 1.4 x 1.6 cm) with suprasellar extension, abutting the optic chiasm, and left cavernous sinus invasion with internal carotid artery encasement. She underwent revision transsphenoidal resection of pituitary tumor to decompress the optic chiasm with plan for subsequent focused radiation to the cavernous sinus portion. Postoperative period was uneventful and hydrocortisone and LT4 were continued on discharge. Final pathology reported silent corticotroph lineage pitNET with low Ki67, immunostaining positive for TPIT, CAM5.2, and negative for ACTH. ACTH-negative SCA are a rare subtype and more likely to have lower ACTH levels, and multiple microcysts on MRI than ACTH-positive SCA. New WHO classification of pitNET highlights the histological typing and subtyping based on immunostaining of pituitary lineage transcription factors as the cornerstone for accurate classification. SCA are more biologically aggressive tumors with a high propensity of recurrence and resistance to conventional treatment. TPIT and ACTH immunostaining significantly improved the diagnosis of SCA and thereby close clinical follow up for early recognition and management of SCA recurrence. Absence of serum markers of recurrence makes this challenging. Presentation: 6/1/2024

12490 Management Of Autoimmune Hepatitis Under Mitotane Therapy: Reintroduction Of Mitotane Under High Dose Corticosteroids For Targeted Mitotane Therapeutic Levels In A Patient With Recurrent Myxoid Adrenocortical Carcinoma

Abstract Disclosure: T. Hristova: None. D. Fenyves: None. C. Cloutier: None. M. Latour: None. Z. El-haffaf: None. P. Karakiewicz: None. H.J. Olney: None. I. Bourdeau: None. Histologically rare variants of adrenocortical carcinoma (ACC) include myxoid, oncocytic and sarcomatoid subtypes. There are about 50 reported cases of myxoid variants up to now that are described as more aggressive than classical ACC with poorer overall survival. Surgical resection offers the best chance of survival, with mitotane being the first line of treatment after surgery. Mitotane is currently the only approved adrenolytic drug for ACC. Among mitotane adverse effects, auto-immune hepatitis (AIH) is reported in monography, yet barely anything is reported in the literature about it. The precise mechanism of AIH has not been reported yet, but the mainstem therapy of AIH is corticosteroids alone or in combination with azathioprine. We report the case of a 43-year-old male who was diagnosed with non-secreting myxoid ACC subtype stage 2 (7x6x5,5 cm, ki67 18%, Weiss score 6/9). Multigene panel testing revealed a germline pathogenic variant in the ATM gene. Post adrenalectomy, mitotane was initiated within 2 months and increased to 2,5g daily within 6 weeks. 11 weeks after starting mitotane, liver enzymes were as follows: ALT 127 U/L (N: 10-39), AST 54 U/L (N: 13-39), ALP 165 U/L (N: 36-110), GGT 489 U/L (N: 9-47), while pre-mitotane levels were normal. Although mitotane was stopped, ALT increased to 255 U/L and remained high for 10 weeks after its cessation. Liver biopsy showed chronic hepatitis with moderate inflammation which was compatible with toxic hepatitis vs AIH. As kinetic liver enzyme tests increased after mitotane cessation, AIH was the retained diagnosis. Treatment with 40mg prednisone daily was then initiated. Pre-prednisone liver enzymes were ALT 202 U/L, AST 64 U/L, ALP 154 U/L, GGT 216 U/L, whereas 8 weeks later values had decreased to ALT 74 U/L, AST 20 U/L, ALP 108 U/L, GGT 84 U/L, and prednisone was lowered to 15mg daily. ACC recurred 3 months later, about one year after the initial adrenalectomy. After surgical resection, mitotane was restarted at 500mg daily with prednisone 40mg daily. As liver enzymes were within normal ranges, mitotane was slowly increased to 2.5g daily, with mitotane plasma levels of 11.3mg/L, whereas prednisone was decreased gradually to 12.5mg daily. Second ACC recurrence occurred one year later and mitotane was further increased to 3g daily under prednisone 12.5mg reaching mitotane levels up to 21.2 mg/L with surgical debulking. Further therapeutic avenues are being considered for a rapid recent ACC recurrence, such as PARP inhibitors for targeted therapy in the context of ATM gene mutation, but further considerations are required due to previous AIH. To the best of our knowledge this is the first reported case of AIH due to mitotane in a rare ACC subtype in a patient carrying a germline ATM gene mutation. We also report restart of mitotane therapy with concomitant high dose prednisone in the context of ACC recurrence that allowed to reach targeted therapeutic levels. Presentation: 6/1/2024

Novel Schiff Bases: Synthesis, Characterization, Bioactivity, Cytotoxicity, and Computational Evaluations

Hypopharyngeal cancer is rare subtype of head and neck cancers with relatively poor prognosis. Current therapeutic modalities lack the potential to provide patients with better clinical outcome and quality of life. This study was conducted on the synthesis of 2-methoxy-4-((3-alkyl(aryl)-5-oxo-1H-1,2,4-triazol-4(5H)-ylimino)-methyl)-phenyl-4-(2-methoxy-4-((3-alkyl(aryl)-5-oxo-1H-1,2,4-triazol-4(5H)-ylimino)-methyl)-phenyl)-4-oxobutanoates (3) using biologically important 1,2,4-triazole. The condensation of 3-alkyl(aryl)-4-amino-4,5-dihydro-1H-1,2,4-triazol-5-ones (1) with 4-formyl-2-methoxyphenyl-4-(4-formyl-2-methoxyphenyl)-4-oxobutanoate yielded the biologically active 2-methoxy-4-((3-alkyl(aryl)-5-oxo-1H-1,2,4-triazol-4(5H)-ylimino)-methyl)-phenyl-4-(2-methoxy-4-((3-alkyl(aryl)-5-oxo-1H-1,2,4-triazol-4(5H)-ylimino)-methyl)-phenyl)-4-oxobutanoates (3). The compounds obtained were analyzed via FT-IR,1H-/13C-NMR spectrometers, elemental analysis, and HRMS spectroscopic techniques. Furthermore, we aimed at investigating the potential of compounds 3a-g against FaDu hypopharyngeal cancer cells. We demonstrated that compounds 3c, 3e, and 3 g had relatively lower IC50 values compared to the remaining tested compounds and more importantly their IC50 values were comparable to 5-FU, which suggests them as important therapeutic agent candidates. These newly synthesized compounds were assessed for their inhibitory activities toward two human carbonic anhydrase isoforms I and II (hCA I and II). Then, molecular docking calculations were made to compare the biological activities of studied molecules against cancer proteins. Compound 3c has a docking score of −7.15 against squamous cell carcinoma protein with ID: 2DO4 and −5.49 docking score against squamous cell carcinoma protein with ID:5PJZ. ADME/T analysis was performed to examine the drug properties of studied molecules.

6450 Leydig Cell Tumor: A Rare Cause of Post-menopausal Hyperandrogenism

Abstract Disclosure: R. Nakdali: None. S. Athimulam: None. Introduction: Ovarian steroid cell tumors are a rare subtype of sex-cord stromal tumors. Leydig cell tumors is a subtype of sex-stromal tumors that is found in < 1% of all ovarian tumors. They are typically benign, unilateral, and secrete androgens which causes virilization. Below we present the case of a postmenopausal woman who presented with signs of virilization and was diagnosed with an ovarian Leydig cell tumor. Case: A 62-year-old postmenopausal woman, with a history of partial hysterectomy with right oophorectomy presented to Endocrinology clinic for evaluation of thyroid nodules. However, clinically she had signs of virilization noted by the provider on examination. She reported progressive androgenic alopecia, cystic acne, oily skin, hoarseness of voice and hirsutism, with increase hair growth over upper lip, chin and jaw line requiring daily shaving. She denied taking any supplements. She reported embarrassment of these physical changes and prior providers had attributed this to aging, therefore not prompting further testing. This caused significant emotional distress to the patient, leading to isolation. Biochemical testing confirmed elevated bioavailable testosterone (193.1 ng/dL) and total testosterone levels (579 ng/dL), with no evidence of hypercortisolemia. Magnetic resonance imaging (MRI) revealed a heterogenous soft tissue mass (2.9 x 2.1 x 2.1 cm) in the left ovary. She underwent a left salpingo-oophorectomy and pathology confirmed a well-differentiated 2.4 cm Leydig cell tumor. Post-operatively, she reported improvement in facial and body hirsutism, reduced shaving frequency decrease in androgenic hair loss, with noticeable hair growth in her frontal scalp, and her skin became less oily with reduced acne. Post-operative labs confirmed cure of hyperandrogenism (Bioavailable testosterone < 2.6 ng/dL; Total testosterone: < 10ng/dL; and Free androgen index < 0.5%). She has been referred to genetics for evaluation. Discussion: Post-menopausal hyperandrogenism poses a diagnostic challenge as it can be mistaken for hormonal imbalances seen with aging. Often times, patients do not report symptoms due to embarrassment unless specifically addressed by provider. Initial testing consists of total and free testosterone and dehydroepiandrosterone sulfate (DHEAS) levels to assess the source of hyperandrogenism. Ruling out hypercortisolemia and assessment for ingestion of testosterone or DHEA supplements is vital. Pelvic ultrasound or cross-sectional imaging (CT or MRI) of abdomen and pelvis can identify structural abnormalities in the ovaries or adrenal glands. Prompt evaluation and management can alleviate significant distress to the patient. Leydig cell tumors represent a rare but important consideration in the differential diagnosis of postmenopausal hyperandrogenism, such as in our patient. Presentation: 6/2/2024

8063 Cystic Parathyroid Adenoma: A Rare Cause Of Severe Hypercalcemia

Abstract Disclosure: M. Owrangi: None. F. Hasan: None. Introduction: Parathyroid adenomas are the most common cause of primary hyperparathyroidism, but within this category, a rare subtype exists - cystic parathyroid adenomas (CPAs). Comprising only 0.5-1% of all parathyroid lesions, CPAs present unique diagnostic and therapeutic challenges. We report a case of a female patient presenting with severe hypercalcemia caused by a CPA. Case presentation: A 44-year-old African American female with a history of nephrolithiasis presented with abdominal pain and signs of dehydration. Labs were remarkable for serum calcium 13.2 mg/dL, albumin 4.0 g/dL, phosphorus 1.8 mg/dL, iPTH 617.7 pg/mL, 25-OH vit D 12.1 ng/mL, creatinine 0.85 mg/dL. She was initially resuscitated aggressively with IV fluids resulting in an improvement in serum calcium level to 10.3 mg/dL. Thyroid US showed a cystic nodule deep to the left thyroid lobe. Sestamibi parathyroid scan was consistent with a left superior parathyroid adenoma. She underwent 2 gland parathyroidectomy 3 months after the initial presentation. Intraoperatively serum PTH decreased by 91% after resection of the 2 parathyroid adenomas. Pathology confirmed the presence of 2 parathyroid adenomas, the larger one measuring 2.8 cm and weighing 3.8 g. Discussion: We describe a case of a middle-aged female presenting with severe hypercalcemia due to CPA. Her initial presentation was concerning for parathyroid carcinoma given the severity of hypercalcemia. However, the radiologic findings, coupled with surgical pathology, indicated that she had CPA. CPAs can be either functional, causing primary hyperparathyroidism (PHPT) with elevated serum calcium levels, or non-functional, remaining asymptomatic. Clinical features of PHPT associated with CPAs are similar to those with solid adenomas and include fatigue, GI symptoms, nephrolithiasis, bone pain, and neuropsychiatric manifestations. However, CPAs may exhibit certain distinct presentations: i) higher pre-operative serum calcium levels; and ii) increased risk of symptomatic hypercalcemia. Despite their rarity, CPAs deserve special attention due to their unique presentation, challenging diagnosis, and potential for severe hypercalcemia. Surgical parathyroidectomy is the definitive treatment for functional CPAs. Accurate localization and complete excision of the adenoma are crucial to avoid recurrence. Most CPAs occur in the fourth and fifth decade of life and are more common in women (female to male ratio of 2.5:1). 65-85% of cases are located in the neck and the majority arise from the inferior parathyroid glands and are left-sided, and may very rarely be intrathyroidal. Presentation: 6/2/2024

6450 Leydig Cell Tumor: A Rare Cause of Post-menopausal Hyperandrogenism

Abstract Disclosure: R. Nakdali: None. S. Athimulam: None. Introduction: Ovarian steroid cell tumors are a rare subtype of sex-cord stromal tumors. Leydig cell tumors is a subtype of sex-stromal tumors that is found in < 1% of all ovarian tumors. They are typically benign, unilateral, and secrete androgens which causes virilization. Below we present the case of a postmenopausal woman who presented with signs of virilization and was diagnosed with an ovarian Leydig cell tumor. Case: A 62-year-old postmenopausal woman, with a history of partial hysterectomy with right oophorectomy presented to Endocrinology clinic for evaluation of thyroid nodules. However, clinically she had signs of virilization noted by the provider on examination. She reported progressive androgenic alopecia, cystic acne, oily skin, hoarseness of voice and hirsutism, with increase hair growth over upper lip, chin and jaw line requiring daily shaving. She denied taking any supplements. She reported embarrassment of these physical changes and prior providers had attributed this to aging, therefore not prompting further testing. This caused significant emotional distress to the patient, leading to isolation. Biochemical testing confirmed elevated bioavailable testosterone (193.1 ng/dL) and total testosterone levels (579 ng/dL), with no evidence of hypercortisolemia. Magnetic resonance imaging (MRI) revealed a heterogenous soft tissue mass (2.9 x 2.1 x 2.1 cm) in the left ovary. She underwent a left salpingo-oophorectomy and pathology confirmed a well-differentiated 2.4 cm Leydig cell tumor. Post-operatively, she reported improvement in facial and body hirsutism, reduced shaving frequency decrease in androgenic hair loss, with noticeable hair growth in her frontal scalp, and her skin became less oily with reduced acne. Post-operative labs confirmed cure of hyperandrogenism (Bioavailable testosterone < 2.6 ng/dL; Total testosterone: < 10ng/dL; and Free androgen index < 0.5%). She has been referred to genetics for evaluation. Discussion: Post-menopausal hyperandrogenism poses a diagnostic challenge as it can be mistaken for hormonal imbalances seen with aging. Often times, patients do not report symptoms due to embarrassment unless specifically addressed by provider. Initial testing consists of total and free testosterone and dehydroepiandrosterone sulfate (DHEAS) levels to assess the source of hyperandrogenism. Ruling out hypercortisolemia and assessment for ingestion of testosterone or DHEA supplements is vital. Pelvic ultrasound or cross-sectional imaging (CT or MRI) of abdomen and pelvis can identify structural abnormalities in the ovaries or adrenal glands. Prompt evaluation and management can alleviate significant distress to the patient. Leydig cell tumors represent a rare but important consideration in the differential diagnosis of postmenopausal hyperandrogenism, such as in our patient. Presentation: 6/2/2024

Macrofollicular subtype of papillary thyroid carcinoma: Ultrasonographic findings and clinical implications.

The macrofollicular subtype of papillary thyroid cancer (MFS-PTC) is a rare subtype often leading to a challenging diagnosis. To evaluate the ultrasonographic (US) features and clinical implication of MFS-PTC. Records of 14 patients histologically diagnosed with MFS-PTC at our institution over a period of 16 years were retrospectively reviewed. Preoperative US features, Bethesda categories determined by fine-needle aspiration (FNA) or core needle biopsy (CNB), and final pathology were assessed in all patients with MFS-PTC. Of the 14 MFS-PTC cases, most nodules were noted as smooth marginated, solid or predominantly solid isoechoic on US and were categorized as low suspicion in 12 cases and intermediate suspicion in 2 cases. The median tumor size was 1.2 cm (range, 0.6-5.6 cm). Of 11 cases that underwent FNA or CNB, 4 (36.4%) with Bethesda category II or III underwent the follow-up because of benign-looking appearance on US and benign results in subsequent CNBs. However, the patients underwent delayed surgery (31.3 months, range 12-41 months) because of serially increased tumor size. Seven patients diagnosed with Bethesda type IV, V, and VI subsequently underwent surgery. Gross extrathyroidal extension into subcutaneous fat tissue and lateral lymph node metastasis were noted in a patient who underwent follow-up. No distant metastases or recurrence was detected. MFS-PTC is representative of a benign sonographic appearance of PTC subtypes. Tumor growth on serial US images is the only suspicious finding for MFS-PTC because FNA or CNB is often false negative.

Anorectal melanoma: systematic review of the current literature of an aggressive type of melanoma.

Anorectal melanoma (ARM) is a rare malignancy often associated with a poor prognosis due to its late diagnosis and aggressive biological behavior. This review aims to comprehensively investigate ARM's diagnosis, management, and treatment, emphasizing its clinical characteristics, laboratory findings, and implications for patient prognosis. A systematic literature search was conducted in PubMed, Embase, and Cochrane CENTRAL databases from inception to 1 July 2024. This review synthesizes existing literature to provide a comprehensive understanding of this rare primary malignancy. A total of 110 articles reporting on 166 patients were included. Gender data were available for 131 cases, comprising 67 females (51.1%) and 64 males (48.9%). The median age was 66 years. The overall median time to diagnosis was 4 months for anal melanoma, 3 months for rectal melanoma, and 4 months for anorectal junction melanoma. The clinical presentation was nodular in 98.2% of cases. Pre-diagnosis symptoms included bleeding in 84.9% of cases, mucous elimination (6%), pain (68.7%), tenesmus (16.9%), and changes in bowel movements (28.5%). Overall survival (OS) was reported in 82 cases, with a median OS of 11 months: 11 months for anal melanoma, 7 months for rectal melanoma, and 12 months for anorectal junction melanoma. ARM is a rare and aggressive melanoma subtype often diagnosed at an advanced stage, leading to a poor prognosis. A female predominance was observed, consistent with other mucosal melanomas. Anal melanoma exhibited better progression-free survival, and OS compared to rectal and anorectal junction melanoma.