Atypical Adenoma Research Articles

PSAT202 A Rare Case of Four-Gland Parathyroid Adenomas

Abstract Background Amongst patients diagnosed with primary hyperparathyroidism, 80% have been identified to have a single parathyroid gland involvement, with 10% involving two glands or more. Case A 71-year-old female with medical history of hypothyroidism, multinodular goiter, CKD stage 3a, recurrent nephrolithiasis and hyperparathyroidism presented for evaluation of hypercalcemia. She was diagnosed with hyperparathyroidism 9 years prior to presentation however she preferred medical management with cinacalcet. For the past 5 months, she had been experiencing worsening fatigue, constipation, body aches and appetite loss. Further blood analysis revealed PTH 1176 pg/mL (14-64 pg/mL), TSH 2.69 uU/mL (0.35-4.94 uU/mL), free T4 1.12 ng/dL (0.60-1.89 ng/dL), vitamin D, 25-Hydroxy 24 ng/mL (30-80 ng/mL), serum calcium 12.6 mg/dl (8.9-10.4 mg/dL), ionized calcium 1.65 mmol/L (1.14-1.33 mmol/L), phosphorus 1.9 mg/dl (2.4-4.8 mg/dl), magnesium 1.0 mg/dl (1.8-3.0 mg/dL). Thyroid ultrasound revealed a left isthmus heterogenous solid nodule measuring up to 2.0 cm and a separate nodule superior to the isthmus measuring up to 0.6 cm. Subsequent NM parathyroid scan was limited due to diffuse uptake of enlarged nodular thyroid. Although limited, imaging did reveal a small focus of uptake lateral to the right lower pole concerning for parathyroid adenoma. A CT 4D neck with and without contrast demonstrated a suspicious parathyroid adenoma posterior to the inferior aspect of the left thyroid measuring up to 1.7 cm, an additional 0.8 cm questionable node, and a 4 cm multicystic mass inferior to the right thyroid lobe concerning for exophytic thyroid nodule or multi cystic parathyroid adenoma. Due to persistence of symptoms and significantly elevated PTH levels concerning for carcinoma, decision was made to undergo a four-gland parathyroid exploration and a right hemithyroidectomy. A right superior parathyroid adenoma was identified; after resection, intraoperative PTH levels failed to improve which prompted further exploration. Left superior and inferior parathyroid adenomas were identified and resected. An ectopic nodule located in the right superior mediastinum with surrounding normal parathyroid tissue was identified and dissected, leaving parathyroid tissue behind. Post operatively, PTH levels appropriately decreased to 54 pg/ml. Pathology of identified parathyroid glands had hypercellular parathyroid tissue with fibrous capsule, consistent with adenomas. Interestingly, the pathology of the presumed ectopic nodule was consistent with atypical parathyroid adenoma. Immunostatins with parafibromin demonstrated nuclear immunoreactivity in the lesional cells, consistent with a benign neoplasm. Patient developed symptomatic hypocalcemia following surgery. She was gradually weaned off calcitriol and is currently normocalcemic. Conclusion It is extremely rare to have adenoma of 4 parathyroid glands simultaneously in the absence of genetic conditions associated with hyperparathyroidism. Age of onset of hyperparathyroidism and absence of other endocrine abnormalities clinically was reassuring, however; further biochemical and genetic testing will be considered in this patient. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

Advances and Updates in Parathyroid Pathology.

Hyperparathyroidism is a common endocrine disorder characterized by elevated levels of parathyroid hormone and hypercalcemia and is divided into 3 types: primary, secondary, and tertiary. Distinction between these types is accomplished by correlation of clinical, radiologic, and laboratory findings with pathologic features. Primary hyperparathyroidism occurs sporadically in 85% of cases with the remaining cases associated with multiple familial syndromes. The pathologic manifestations of primary hyperparathyroidism include parathyroid adenoma, parathyroid hyperplasia, and parathyroid carcinoma. Recent advances in the understanding of the pathogenesis of parathyroid disease has helped to refine the diagnosis and classification of parathyroid lesions. The identification of multiple clonal proliferations in traditional multiglandular parathyroid hyperplasia has led to the adoption by the World Health Organization (WHO) of the alternate term of primary hyperparathyroidism-related multiglandular parathyroid disease. Additional nomenclature changes include the adoption of the term atypical parathyroid tumor in lieu of atypical parathyroid adenoma to reflect the uncertain malignant potential of these neoplasms. Clinical and morphologic features characteristic of familial disease have been described that can help the practicing pathologist identify underlying familial disease and provide appropriate management. Use of ancillary immunohistochemistry and molecular studies can be helpful in classifying parathyroid neoplasms. Parafibromin has proven useful as a diagnostic and prognostic marker in atypical parathyroid tumors and parathyroid carcinomas. This review provides an update on the diagnosis and classification of parathyroid lesions considering the recent advances in the understanding of the molecular and clinical features of parathyroid disease and highlights the use of ancillary studies (immunohistochemical, and molecular) to refine the diagnosis of parathyroid lesions.

PSUN76 Massive Four-Gland Parathyroid Hyperplasia: The Case of the Missing Glands

Abstract Introduction Parathyroid adenoma (PA) and parathyroid hyperplasia (PH) are common causes of primary hyperparathyroidism (PHPT) for which the only definitive treatment is surgical removal. Surgery is often preceded by imaging for localization, including by ultrasound (US), Sestamibi scan (MIBI), positron emission tomography/computer tomography (PET/CT), and four-dimensional computed tomography (4D-CT). While it is common for parathyroid pathology to not be visualized on imaging, non-visualization is more typical of adenomas and hyperplasia of smaller size. Clinical Case A 65-year-old male without history of kidney dysfunction or family history of parathyroid disease was referred to surgery for parathyroidectomy to manage longstanding PHPT. Serology showed a parathyroid hormone (PTH) level of 581 pg/mL (reference range: 12-65 pg/mL) and calcium of 11.8 mg/dL (reference range: 8.6-10.5 mg/dL). Preoperative parathyroid localization US revealed a large well-defined 1.5 cm PA. The patient underwent parathyroidectomy, which detected a large right inferior parathyroid gland, confirmed with pathology to be an atypical parathyroid adenoma weighing 1800 mg. Postoperative PTH level was 550 pg/mL and calcium was 12.6 mg/dL. MIBI did not display any definite parathyroid adenoma or ectopic parathyroid tissue. Further evaluation with PET/CT did not demonstrate any evidence of metabolically active residual or ectopic parathyroid adenoma or metastatic disease, and repeat US showed did not reveal evidence of any abnormal parathyroid tissue. Ultimately, 4D-CT detected a multiglandular parathyroid with a 1.8×1.4×3.0 cm right superior adenoma weighing approximately 3931 mg, 1.2×0.8×2.1cm left superior adenoma weighing approximately 1048 mg, and a 0.3×0.4×0.4cm left superior adenoma weighing approximately 25 mg. The patient underwent re-exploration parathyroidectomy with removal of the right superior adenoma weighing 3105 mg and left superior adenoma weighing 1100 mg. The remaining left inferior gland was biopsied and the majority of it was implanted into the arm. Repeat serology one week post-operatively showed improvement of PTH level to 5 pg/mL and of calcium to 8.9 mg/dL and serology one year post-operatively showed a PTH level of 82 pg/mL and a calcium of 9.4 mg/dL. Conclusion We present a patient with massive four-gland PH who initially presented with findings more typical of PA, but ultimately had additional hyperplasic glands that were identified after removal of the adenomatous gland. These glands were unusually large to be seen in PH and yet still be undetected on multiple imaging modalities; no previously reported non-ectopic hyperplastic glands of this size have been documented that were not detected on US or MIBI. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

PSAT198 Atypical Parathyroid Adenoma is an Unusual Cause of Primary Hyperparathyroidism

Abstract Background Atypical parathyroid adenomas (APA) are considered tumors of uncertain malignant potential and have a biochemical and clinical phenotype that is generally more aggressive than typical parathyroid adenomas (PA). Low incidence as an etiology of primary hyperparathyroidism (PHPT) presents a challenge in understanding the pathological features and natural history of APA. We present a case of PHPT due to an APA and review the published literature for these tumors. Case A 37 year-old male was referred for evaluation of hypercalcemia, with serum calcium level 13.6 mg/dL (8.6-10.3). Repeat serum calcium measurement was 12.7 mg/dL, and two measurements of intact PTH were 870 pg/mL and 919 pg/mL (12-88), respectively. The patient's laboratories raised concern for parathyroid carcinoma (PC), but there was no palpable neck mass and no enlarged parathyroid glands were visualized on ultrasonography. Parathyroid scintigraphy was notable for faint but persistent Tc-99 m sestamibi uptake in the left inferior neck. Additional preoperative evaluation revealed significantly reduced bone mineral density in the distal third of the radius (0.638 g/cm2, Z-score -3.2), silent nephrolithiasis of the right kidney, and vitamin D deficiency (25-OH vitamin D 13.4 ng/dL, 30-100). An unequivocally enlarged (175 mg, 2.5 cm in largest diameter) left inferior parathyroid gland was removed, with the remaining glands unremarkable by inspection. Extensive nuclear atypia and cellular pleomorphism indicated an APA, and invasive features of PC were absent. One month after surgery, serum calcium improved to 10.2 mg/dL and intact PTH was 40 pg/mL. Conclusions APA account for 1-2% of PHPT cases. This patient's case has several features that distinguish it from a PA including degrees of preoperative hypercalcemia and intact PTH elevation, low vitamin D level, significantly reduced bone density in the distal third of the radius, nephrolithiasis, relatively young age, and male gender. Fibrous bands, pseudocapsular invasion, and trabecular growth pattern are the most common histologic features of APA, but nuclear atypia and cellular pleomorphism are well established diagnostic criteria. APA may be biochemically similar to PC but are distinguished from PC by the absence of gross invasion into adjacent anatomic structures, distant metastases, and vascular or perineural invasion. Additionally, CDC73 mutations are present in nearly all cases of PC but not in APA. Over 90% of patients with APA are successfully treated by parathyroidectomy. Careful follow up of APA patients is recommended, though there are no specific guidelines regarding a minimum satisfactory duration of postsurgical monitoring. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

PSAT176 Molecular Analysis of AMBRA1 as a Candidate Tumor Suppressor in Sporadic Parathyroid Adenomas

Abstract Primary hyperparathyroidism is a common endocrine disorder that is most often caused by a sporadic single-gland parathyroid adenoma. Currently, the only known and experimentally validated oncoprotein for parathyroid adenomas is cyclin D1. The overexpression of cyclin D1 protein has been reported in twenty to forty percent of cases. Eight percent of this overexpression can be explained by DNA rearrangement involving the cyclin D1 locus. The remaining molecular mechanisms behind this overexpression have yet to be identified. In this study, we explored a potential parathyroid tumorigenic mechanism that could increase cyclin D1 stability through a defect in the AMBRA1 E3 ligase adaptor, a molecule responsible for its degradation. Evidence that AMBRA1 may be a tumor suppressor gene includes the accumulation of cyclin D with hyperproliferation in AMBRA1-deficient cells, the context-dependent growth of tumors in Ambra1-deficient mice, and the finding that low levels of AMBRA1 correlated with poor clinical outcomes in The Cancer Genome Atlas (TCGA). We have therefore proceeded examine AMBRA1 for evidence of tumor suppressor-type inactivation within a cohort of parathyroid adenomas. Genomic DNA from twenty-six typical sporadic parathyroid adenomas was subjected to PCR-amplification of all eighteen coding exons of AMBRA1, followed by Sanger sequencing. Sequences were analyzed by comparison to the normal reference sequence, seeking to assess any observed intragenic or splice-site variants as potential or likely loss-of-function mutations. Thus far, with ninety-seven percent of the coding region fully sequenced, no intragenic AMBRA1 inactivating mutations were observed. Three known single nucleotide polymorphisms, considered non-pathogenic, were identified: missense variant c.3028G>T, and 3' UTR variants c.*491T>C and c.*576A>T, each in a single tumor. Future study of increased numbers of parathyroid adenomas is needed to exclude the possibility that AMBRA1 inactivation could play a driver role in a small percentage of cases, and the possibility that AMBRA1 might contribute less directly e.g. via secondarily altered expression also warrants investigation. Nonetheless, our current observations strongly suggest that AMBRA1 does not have a frequent role as a classic 2-hit tumor suppressor gene in sporadic parathyroid adenomas. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

Parathyroid carcinoma during pregnancy: a novel pathogenic CDC73 mutation – a case report

BackgroundParathyroid carcinoma is an uncommon cause of PTH-dependent hypercalcemia. Only a handful of cases have been reported of parathyroid carcinoma during pregnancy.Case presentationTwenty-four – Year – old female presented with proximal myopathy was found to have hypercalcemia. Her serum corrected total calcium was – 15 mg/dl (8.5 – 10.3), serum phosphate – 2.3 mg/dl (2.5 – 4.5), intact PTH – 118 pg/ml (20 – 80), Vitamin D – 15 ng/ml and Urine Ca/Cr ratio – 2.1 (0.1 – 0.2). Her CECT–neck revealed a well-defined mass lesion posterior to the right lobe of the thyroid – 2.6 cm × 2.5 cm × 2.9 cm in size. She was started on vitamin D supplementation, and she underwent right lower focal parathyroidectomy. Her PTH levels normalized following surgery. Her histology revealed an atypical parathyroid adenoma. She was treated with calcium and vitamin D. Her follow up was uneventful.One year following initial surgery the patient became pregnant and at 16 weeks of POA, the patient presented with a rapidly enhancing neck mass for one week duration. Her biochemical investigations were suggestive of a recurrence of primary hyperparathyroidism. Her ultrasound scan of the neck revealed a well-defined discreate hypoechoic nodule, superior to the thyroid isthmus which was confirmed by a non-contrast MRI scan of the neck. She underwent an uncomplicated second trimester parathyroid tumour excision with normalization of post op PTH. Her histology revealed a parathyroid carcinoma with vascular and capsular invasion. Her genetic studies revealed a novel frameshift mutation of the CDC73 gene. She was treated with calcium and vitamin D supplementation and closely followed up with ionized calcium and PTH levels which were normal throughout the pregnancy. She had an uncomplicated caesarean section at a POA of 37 weeks. Currently she is twelve weeks post-partum, in remission of disease.ConclusionThis case shows the importance of stringent follow up of atypical parathyroid adenoma patients, the benefit of second trimester surgery in management of hypercalcemia due to parathyroid carcinoma during pregnancy and the importance of identifying the novel CDC73 gene mutation.

Recurrence Rate and Exploration of Clinical Factors after Pituitary Adenoma Surgery: A Systematic Review and Meta-Analysis based on Computer Artificial Intelligence System.

Background The first-line treatment for patients with any type of pituitary adenoma is trans-sphenoidal surgery. Considering the prevalence of the condition globally, the treatment is quite common. The recurrence of pituitary adenoma is a recognized occurrence in the medical field; however, there is limited comprehensive research and analysis of the predictive factors of recurrence rates and the clinical factors impacting relapse rates. Identifying the recurrence rates of pituitary adenomas and the clinical factors associated with them could help increase the remission rate by increasing focus on the specific aspects for early diagnosis and improved treatment. Objective The objective of the current systematic review and meta-analysis is to assess the recurrent rates based on previous studies and to explore the clinical factors after pituitary surgery. Methods A search was performed on PubMed, APA PsycINFO, Scopus, CENTRAL, and Google Scholar databases for English articles published from 1st January 2010 to 1st August 2022. Systematic reviews, meta-analysis, evidence syntheses, editorials, commentaries, preclinical studies, abstracts, theses, and preprints were excluded. Meta XL statistical software was used to conduct a prevalence meta-analysis. Results PubMed, PsycINFO, and Medline databases were searched. All of the articles were written between 2012 and 2022. In the beginning, 612 items were recognized. After removing duplicates and analyzing the remaining articles in terms of inclusion and exclusion criteria, 31 articles remained. Conclusion There is a relationship between recurrence rates and the follow-up period. There were conflicting results about the clinical factors after pituitary adenoma surgery, specifically age and tumor size. Some included studies that there was an association between macroadenomas and high recurrence rates. No study reported that gender was a clinical factor affecting pituitary adenoma surgery outcomes or the recurrence rate. Studies also reported that there was a correlation between the remnant tumor factor and the recurrence rates; adenoma remnants after surgery increased the risk of recurrence rates for patients.

Atypical metanephric adenoma: Shares similar histopathological features and molecular changes of metanephric adenoma and epithelial-predominant Wilms' tumor.

BackgroundMetanephric adenomas (MAs) are rare, benign renal tumors. Wilms’ tumors (WTs) are malignant embryonic tumors that originated from nephrogenic blastemal cells. However, some tumors have similar morphology to both MA and epithelial-predominant WT, which makes differential diagnosis difficult. We aimed to analyze the morphological, immunophenotypic and molecular changes in overlapping cases to explore their attribution.Methods and resultsTwenty MAs, ten WTs, and nine cases with MA/WT overlapping histological features were studied. Twenty tumors demonstrated the typical morphological spectrum of MA with high cellularity and were composed of tightly packed small, uniform, round acini with a lower Ki67 index. Almost all MAs (94.7%, 18/19) were detected with BRAF V600E mutation. The ten WTs were epithelial-predominant WTs with glands, rosettes and glomerular structures, which also showed a higher Ki-67 index (up to 60%), invasive growth patterns, and a lack of BRAF mutation. However, the other nine overlapping cases showed two components: typical MA-like areas and epithelial WT-like areas. The cells of the WT-like areas were tubular, columnar and showed marked cytological atypia, with a Ki-67 proliferative index of up to 30%. The immunophenotype of these overlapping lesions was not significantly different from that of typical MA and they positively expressed WT1 and CD57. The BRAF V600E mutation was detected in both WT-like and MA-like areas in nine overlapping tumors. The follow-up data of 31 patients were analyzed, with a median follow-up time of 66 months (range, 8-45 months). Even though most patients with WT underwent radiotherapy or chemotherapy after surgery, two died, and one had liver metastasis. No MA or overlapping cases showed any evidence of recurrence or metastasis after surgery.ConclusionsThe molecular changes in tumors with overlapping morphological features were the same as those of typical MA; thus, we think that these tumors should be classified as MA and further called atypical MA. It is important to note that atypical MA is not a neglected subtype of MA. It possesses different histological morphology and a higher Ki-67 index but has the common imaging characteristics, immunophenotype and gene expression as typical MA, and patients usually have a good prognosis.

Spontaneous Occurrence of Various Types of Hepatocellular Adenoma in the Livers of Metabolic Syndrome-Associated Steatohepatitis Model TSOD Mice.

Male Tsumura-Suzuki Obese Diabetes (TSOD) mice, a spontaneous metabolic syndrome model, develop non-alcoholic steatohepatitis and liver tumors by feeding on a standard mouse diet. Nearly 70% of liver tumors express glutamine synthetase (GS), a marker of hepatocellular carcinoma. In contrast, approximately 30% are GS-negative without prominent nuclear or structural atypia. In this study, we examined the characteristics of the GS-negative tumors of TSOD mice. Twenty male TSOD mice were sacrificed at 40 weeks and a total of 21 tumors were analyzed by HE staining and immunostaining of GS, liver fatty acid-binding protein (L-FABP), serum amyloid A (SAA), and beta-catenin. With immunostaining for GS, six (29%) tumors were negative. Based on the histological and immunohistological characteristics, six GS-negative tumors were classified into several subtypes of human hepatocellular adenoma (HCA). One large tumor showed generally similar findings to inflammatory HCA, but contained small atypical foci with GS staining and partial nuclear beta-catenin expression suggesting malignant transformation. GS-negative tumors of TSOD mice contained features similar to various subtypes of HCA. Different HCA subtypes occurring in the same liver have been reported in humans; however, the diversity of patient backgrounds limits the ability to conduct a detailed, multifaceted analysis. TSOD mice may share similar mechanisms of HCA development as in humans. It is timely to review the pathogenesis of HCA from both genetic and environmental perspectives, and it is expected that TSOD mice will make further contributions in this regard.

S182 Estimating the Prevalence and Characteristics of Colorectal Neoplastic Lesions in Young Patients Undergoing Colonoscopy

Introduction: Incidence of colorectal neoplasia (CRN) in patients < 50 years of age has been increasing. Although current guidelines recommend starting screening at age 45, data on the prevalence and characteristics of CRN in this cohort is sparse. We aim to determine the overall prevalence and characteristics of CRN lesions in patients < 50. Methods: All patients < 50 years who underwent colonoscopy for any indication between Jan 2012 and Dec 2018 were included. Data on demographics, comorbidities, risk factors and indications was obtained. Procedural data on number of polyps and polyp characteristics was collected. Patients with inadequate preparation, personal history of (h/o) colon polyps or cancer and inflammatory bowel disease were excluded. Logistic regression analysis was used to determine predictors of adenoma detection. Results: 4587 patients had diagnostic colonoscopy during the study period. Mean age was 38.1 years, with 61.2% females, 84% white. Abdominal pain (36%), family h/o CRC (29.5%), diarrhea (29.3%), hematochezia (25.7%) and constipation (21.2%) were the most common indications. Information on clinical characteristics based on age groups are shown in Table. 26.2% (n=1201) had at least one polyp; 14.8%, 31.9% and 39.4% were < 39, 40-44 and 45-49 years of age respectively. Overall adenoma prevalence was 15.8%; 7.81%, 19.9% and 24.9% were < 39, 40-44 and 45-49 respectively. ≥ 3 adenomas were observed in 6.9%; prevalence increased with age (Figure 1a). Majority of the polyps were tubular adenomas (45.6%), followed by sessile serrated adenomas (17.2%); tubulovillous adenomas were the least common (2.7%). High-grade dysplasia and carcinoma were observed in 0.4% and 0.8% (Figure 1b). On multivariate analysis of 1602 patients (801 with polyps and 801 age-sex matched controls), female sex (OR 0.79) and age < 39 (OR 0.63) were associated with lower odds, while family h/o polyps (OR 1.76) and BMI (1.04) were associated with higher odds of adenoma detection (Table). Conclusion: There was an increasing trend in the prevalence of polyps, adenomas, advanced adenomas and CRC with increasing age; our rates were similar to other published studies. Prevalence rates for all the above doubled between age groups < 39 and 40-44, but with a smaller proportion of increase between 40-44 and 45-49. Large population studies are needed to confirm this observation. Male gender, increasing age, obesity and family h/o colon polyps were independent predictors of adenoma detection in our cohort. Table 1. - Demographics, Clinical Characteristics and Logistic Regression Demographics Age < 39 Age 40-44 Age 45-49 All Age Groups p-value Total number of patients 2152 1036 1399 4587 Patients with ≥ 1 polyp, n 319 331 551 1201 Clinical Characteristics, Comorbidities and Risk Factors Mean BMI (+/-SD) 32 (10.1) 32.4 (9.5) 32.7 (9.4) 32.4 (9.6) 0.3128 Diabetes, n (%) 16 (5) 29 (8.8) 42 (7.6) 87 (7.3) 0.1591 Hypertension, n (%) 37 (11.6) 55 (16.7) 146 (26.6) 238 (19.9) < .0001 Tobacco use, n (%) 112 (35.2) 107 (32.4) 180 (32.9) 399 (33.4) 0.7137 NSAID use, n (%) 76 (23.9) 73 (22.3) 128 (23.3) 277 (23.2) 0.8904 Statin use, n (%) 7 (2.2) 20 (6.1) 67 (12.2) 94 (7.9) < .0001 Multivariate Analysis Predictor Reference OR 95% CI (UL, LL) p-value Age 40-44 ≤ 39 45-4945-49 0.490.63 0.75, 1.180.5, 0.79 0.59 < 0.001 Gender Male 0.79 0.65, 0.95 0.011 BMI Per each unit ↑ 1.04 1.03, 1.05 < 0.001 Diabetes No 0.81 0.56, 1.19 0.29 Hematochezia No 0.96 0.77, 1.19 0.71 Anemia No 1.22 0.87, 1.71 0.25 Family h/o colon polyps No 1.76 1.03, 1.05 < 0.01 Family h/o colon cancer No 1.18 0.94, 1.48 0.15 Figure 1.: Prevalence rates of polyps, adenomas and advanced adenomas (1a) and different types of adenomas, high grade dysplasia and carcinoma (1b)

CASE REPORT: POST-MEGASTENT DUODENAL POLYP

Introduction&#x0D; Most duodenal polyps are non-neoplastic. Instead, they represent regenerative/hyperplastic nodules of foveolar epithelium or Brunner gland proliferation (38%). Other less common polyps include heterotopic (6%) and neoplastic lesions (11%) (1). Adenomas of intestinal type are the most common (89%), followed by adenomatous lesions that present a gastric phenotype: PGAs (8%) and foveolar-type adenomas (3%) (2).&#x0D; Non-neoplastic duodenal polyps, most of which represent regenerative inflammatory (pseudo) polyps, are predominantly localized in the bulb (80%) (1). The majority are associated with duodenitis, especially in the setting of peptic injury, and are less commonly associated with inflammatory bowel disease or rare conditions such as primary immunodeficiencies. (3). Histologically, non-neoplastic duodenal polyps may resemble gastric hyperplastic polyps and frequently show metaplastic foveolar epithelium with active inflammation and/or erosion, reactive epithelial changes, seamless transition with the surrounding epithelium, and surface maturation. They may also simply be composed of granulation tissue. It is worth underscoring that some of these polyps are neoplastic. Some hyperplastic polyps harbor KRAS and BRAF mutations and tend to show serrated features, similar to their microvascular colonic counterparts (4). Duodenal hyperplastic polyps with KRAS mutation may represent precursor lesions of duodenal traditional serrated adenomas (4). The polypoid heterotopic gastric mucosa is another frequent type of duodenal polyps. As opposed to the peptic injury-induced foveolar metaplasia, lesions of this type also contain clusters of oxyntic glands under the surface of the foveolar epithelium. Duodenal gastric heterotopia is associated with FGPs and PPI therapy.

The roles of the tumor suppressor parafibromin in cancer.

In this review, we discuss parafibromin protein, which is encoded by CDC73. A mutation in this gene causes hyperparathyroidism-jaw tumor (HPT-JT) syndrome, an autosomal dominant disease. CDC73 is transcriptionally downregulated by the Wilms’ tumor suppressor gene WT1 and translationally targeted by miR-182-3p and miR-155. In the nucleus, parafibromin binds to RNA polymerase II and PAF1 complex for transcription. Parafibromin transcriptionally increases the expression of c-Myc, decreases CPEB1 expression by interacting with H3M4, and reduces cyclin D1 expression by binding to H3K9. The RNF20/RNF40/parafibromin complex induces monoubiquitination of H2B-K120, and SHP2-mediated dephosphorylation of parafibromin promotes the parafibromin/β-catenin interaction and induces the expression of Wnt target genes, which is blocked by PTK6-medidated phosphorylation. Parafibromin physically associates with the CPSF and CstF complexes that are essential for INTS6 mRNA maturation. In the cytosol, parafibromin binds to hSki8 and eEF1Bγ for the destabilization of p53 mRNA, to JAK1/2-STAT1 for STAT1 phosphorylation, and to actinin-2/3 to bundle/cross-link actin filaments. Mice with CDC73 knockout in the parathyroid develop parathyroid and uterine tumors and are used as a model for HPT-JT syndrome. Conditional deletion of CDC73 in mesenchymal progenitors results in embryos with agenesis of the heart and liver while its abrogation in mature osteoblasts and osteocytes increases cortical and trabecular bone. Heterozygous germline mutations in CDC73 are associated with parathyroid carcinogenesis. The rates of CDC73 mutation and parafibromin loss decrease from parathyroid adenoma to atypical adenoma to carcinoma. In addition, down-regulated parafibromin is closely linked to the tumorigenesis, subsequent progression, or poor prognosis of head and neck, gastric, lung, colorectal, and ovarian cancers, and its overexpression might reverse the aggressiveness of these cancer cells. Therefore, parafibromin might be useful as a biological marker of malignancies and a target for their gene therapy.

Case of clinically "aggressive" course of primary hyperparathyroidism, algorithm of differential diagnosis

Primary hyperparathyroidism (PHPT) is a significant endocrine disease caused by increased production of parathyroid hormone (PTH) by altered parathyroid glands and violation of the mechanisms of regulation of serum calcium concentrations. These changes can lead to nephrolithiasis, osteoporosis, erosive and ulcerative lesions of the gastrointestinal tract, a number of less specific symptoms (nausea, vomiting, weakness, fatigue, etc.). Etiologically, in more than 85% of cases, PHPT is a consequence of sporadic solitary adenoma or hyperplasia parathyroid glands, however, in 1-3% of cases, the cause is carcinoma of parathyroid glands , including as part of various genetic syndromes. The importance of timely examination for PHPT of patients with characteristic clinical manifestations of this disease and - with an aggressive course - alertness towards carcinomas of parathyroid glands was noted. At the same time, the severity of the clinical picture and even the presence of suspicious signs characteristic of hereditary forms of carcinomas of parathyroid glands are not always a consequence of the malignant process. We present a description of a young patient with a severe course of PHPT, multiple fractures and a voluminous tumor of the upper jaw, developed as a result of a typical adenoma of parathyroid glands. Additionally, the algorithm of pre- and postoperative differential diagnosis for such patients is highlighted.

Evaluation of autoantibody signatures in pituitary adenoma patients using human proteome arrays.

To identify the specific diagnostic biomarkers related to pituitary adenomas (PAs), we performed serological antibody profiles for three types of PAs, namely Acromegaly, Cushing's and Nonfunctional Pituitary Adenomas (NFPAs), using the human proteome (HuProt) microarray. This is the first study describing the serum autoantibody profile of PAs. We performed serological autoantibody profiling of four healthy controls, four Acromegaly, three Cushing's and three NFPAs patient samples to obtain their autoantibody profiles, which were used for studying expression, interaction and altered biological pathways. Further, significant autoantibodies of PAs were compared with data available for glioma, meningioma and AAgAtlas for their specificity. Autoantibody profile of PAs led to the identification of differentially expressed significant proteins such as AKNAD1 (AT-Hook Transcription Factor [AKNA] Domain Containing 1), NINJ1 (Nerve injury-induced protein 1), L3HYPDH (Trans-3-hydroxy-L-proline dehydratase), RHOG (Rho-related GTP-binding protein) and PTP4A1 (Protein Tyrosine Phosphatase Type IVA 1) in Acromegaly. Protein ABR (Active breakpoint cluster region-related protein), ST6GALNAC6 (ST6 N-acetylgalactosaminide alpha-2, 6-sialyltransferase 6), NOL3 (Nucleolar protein 3), ANXA8 (Annexin A8) and POLR2H (RNA polymerase II, I and III subunit H) showed an antigenic response in Cushing's patient's serum samples. Protein dipeptidyl peptidase 3 (DPP3) and reticulon-4 (RTN4) exhibited a very high antigenic response in NFPA patients. These proteins hold promise as potential autoantibody biomarkers in PAs.

CARCINOMA EX-PLEOMORPHIC ADENOMA: A CASE REPORT

A 37-year-old afrodescendant man presented a nodular lesion on the palate, with 2 years of evolution and history of pain and ulceration in the last 6 months. The provisional diagnosis was salivary gland neoplasia. An incisional biopsy revealed areas of typical pleomorphic adenoma (PA) associated with mucous, clear and atypical squamous cells, and cystic spaces. Immunohistochemical positivity for AE1/AE3, CK 7, CK14, CK19, p63, and Ki-67 (30%) was observed. The diagnosis was carcinoma ex-pleomorphic adenoma (CEPA). The tumor was resected, with a safety margin, and complementary chemo and radiotherapy were performed. No recurrence was observed after 1 year of follow-up. CEPA represents a malignant change in a pre-existing PA, which is extremely uncommon in minor salivary glands. Despite the rarity, this tumor must be considered in the differential diagnosis of intraoral salivary gland tumors with sudden changes in their clinical behavior.

Glucocorticoids and mineralocorticoids in blood plasma as markers of early diagnostic adrenal cortical tumors

Adrenocortical tumours of the adrenal glands are formed when the cells of the cortical layer grow. The morphological and histological structure of benign adrenal tumours is variable, which complicates their early diagnosis. The study of the levels of hormones in the adrenal cortex along with the analysis of the symptoms of the disease will allow not only to differentiate hormone-producing tumours, but also to predict the direction of metabolic processes, which will make it possible to choose the right treatment regimen and prevent complications from other organs.&#x0D; The aim of the study is to determine the level of cortisol and aldosterone and assess the state of the pituitary-adrenal and renin-aldosterone systems in patients with various types of adrenocortical adenomas.&#x0D; Materials and methods. The state of the hormonal status of the adrenal cortex was assessed by determining the level of glucocorticoids - cortisol and mineralocorticoids - aldosterone using a direct quantitative enzyme immunoassay. The level of adrenocorticotropic hormone (ACTH) and renin was determined by immunochemical methods using monoclonal antibodies specific for ACTH and renin.&#x0D; Research results. An increase in the level of cortisol was detected against the background of a decrease in the level of ACTH in patients with cortisol-producing adrenocortical adenomas. It is shown that the aldosteronism we discovered in patients with aldosterone-producing adenomas develops against the background of an unchanged renin level and an increase in the aldosterone/renin ratio.&#x0D; Conclusions. The development of hormone-dependent adenomas of the adrenal cortex is accompanied by an imbalance in the work of the pituitary-adrenal and renin-aldosterone systems, the direction of changes of which can serve as a criterion for early diagnosis of adrenocortical adrenal adenomas

Innovative Approach of Endosonographic Radioactive Labeling of an Ectopic Parathyroid Adenoma by Technetium-99m Human Serum Albumin: A Case Report

Primary hyperparathyroidism caused by parathyroid adenoma requires surgical resection. To confine the extent of surgery to the very minimum and to exclude an atypical adenoma location, preoperative imaging aims at identifying the suspicious gland. For this purpose, Technetium-99m (99mTc)-sestamibi scintigraphy and SPECT have become the international imaging standard, in inconclusive cases also with C-11 methionine and F-18 choline PET/CT. We present a case of surgery for an ectopic retroesophageal adenoma resected under gamma probe guidance after preoperative radioactive targeting. A 73-year-old patient, who was diagnosed with primary hyperparathyroidism, presented to our outpatient clinic. The patient was symptom-free, but during a routine check-up, parathormone levels of 127 pg/ml (normal range 15-65) were detected. Parathyroid MIBI scintigraphy, including SPECT/CT, failed to locate an adenoma. Therefore, a PET/MRI scan with 164 MBq F-18 choline was applied and a single parathyroid adenoma was detected in a very untypical retroesophageal and prevertebral position, respectively. Due to its esophageal proximity and to enable a very confined surgery, endosonography was performed and the adenoma was transesophageally injected with 75 MBq 99mTc-human serum albumin (HSA). The next day gamma probe-guided minimally invasive resection was performed without any intra- or postoperative complications. Minimally invasive resection of parathyroid adenomas should be the standard but may be difficult in deep collar and atypical locations. Marking the adenoma with a radioactive nanocolloid tracer for gamma probe-guided surgery can be considered an innovative approach to maintain minimal invasive therapy for ectopic adenomas.

Frequency of Functional and Non-Functional Pituitary Adenomas in Patients Presented at Ayub Teaching Hospital, Abbottabad

Objective: Pituitary lesions cause morbidity and mortality in all age groups due to their hormonal hypersecretion, its mass effects, and post-surgery complications. The present study determined the frequency of functional and non-functional pituitary adenomas.&#x0D; Materials &amp; Methods: The study included patients (n = 114) presenting with functional and non-functional pituitary adenoma. Pituitary adenomas were diagnosed based on MRI brain with contrast and the size of the tumor was noted a tumor having a size of 10 mm or more was labeled as macro adenoma and a tumor having a size less than 10 mm was labeled as microadenoma. Pituitary adenomas were stratified among age, gender, duration of symptoms, types of adenomas, types of functional adenoma, and type of the tumor on a size basis.&#x0D; Results: Most of the patients had TSH- secreting adenoma (21.9%). 52.6% were found with microadenoma and 47.4% had macro adenoma. Patients with functional adenoma were 30.7% and with non-functional adenoma 32.5% were male while patients with functional adenoma were 26.3% and with non-functional adenoma 10.5%were female (p = 0.018). Patients with functional adenoma (43.9%) and non-functional adenoma (8.8%) were found to have microadenoma, whereas patients with functional adenoma (13.2%) and non-functional adenoma (34.2%) were found to have macroadenoma (p = 0.000). Patients with functional adenoma having a duration of symptoms below 1 year were 11 (9.6%), 1 to 3 years were 25 (21.9%), 17 (14.9%) were 4 to 6 years, and 12 (10.5%) above 6 years duration of symptoms.&#x0D; Conclusion: Patients with pituitary adenomas should be diagnosed early to receive successful therapy.

Case Report: Functioning adrenal adenoma presenting with atypical imaging findings

The most common adrenal lesion is an adrenal adenoma in adults. Adrenal adenomas can have a variety of imaging features due to their widespread prevalence. As a result, distinguishing between typical and atypical imaging features of adrenal adenomas is critical, as is distinguishing atypical adrenal adenomas from potentially malignant lesions. Here, we present a case of adrenal adenoma with atypical imaging findings presenting as Cushing’s syndrome.

Hyperprolactinemia following traumatic myelopathy

Abstract Prolactin, an anterior pituitary gland hormone, is necessary for breast development in pregnancy and initiation of lactation. Prolactinomas constitute a pathological cause of elevated serum prolactin levels and are the most common type of pituitary adenomas. Excess prolactin could result from physiological causes that include pregnancy, lactation, sleep, and coitus. The usual presentation of hyperprolactinemia is galactorrhea. There are reports of elevated prolactin levels following other pathological causes such as chest wall lesions, chest wall trauma, and medications. We report the rare association of hyperprolactinemia with traumatic injury to the spinal cord in a Nigerian patient, and a brief review of the relevant literature.