Atypical Adenoma Research Articles

P-19 A PATIENT WITH ATYPICAL PARATHYROID ADENOMA

Abstract Introduction Primary hyperparathyroidism is most frequently caused by a parathyroid adenoma, occasionally by parathyroid hyperplasia, rarely by atypical parathyroid adenoma and parathyroid carcinoma. Here, we present a case diagnosed as PHPT pathology revealed atypical parathyroid adenoma. Clinical Case A 49-year-old male patient was referred to our endocrinology clinic because of hypercalcemia identified for the investigation of nephrolithiasis. The patient reported no hypercalcemia-related symptoms. His physical checkup was unremarkable. The results of the laboratory investigations were as follows: calcium 10.9 mg/dL (8.8–10.6), albumin 4.2 g/dL (3.5–5.2), phosphorus 2.15 mg/dL (2.5–4.5), 25-OH vitamin D 13 μg/L, PTH 142 ng/L (15–65), creatinine 0.59 mg/dL (0–1.2), and 24-hour urine calcium 647.4 mg/day (0–300). Neck ultrasonography revealed two hypoechoic nodules, the biggest measuring 13.5 x 9 mm in the right thyroid lobe. Parathyroid scintigraphy revealed no typical signs consistent with a parathyroid adenoma in the neck or mediastinum. Four-dimensional computed tomography of the neck revealed an 8 mm, well-circumscribed, bilobed lesion in the posterior-inferior region of the right thyroid lobe, that did not augment with intravenous contrast and was regarded as an exophytic thyroid nodule. A fine-needle aspiration biopsy was done and the results were reported as follicular lesions of uncertain significance. A PTH washout test was performed on the same nodule, resulting in a value of almost 5000 ng/L. A choline PET/CT scan revealed a 13 mm soft tissue lesion with enhanced radiotracer uptake (SUV max: 5.39) posterior to the lower pole of the right thyroid lobe, indicating a parathyroid adenoma. The patient underwent a right thyroid lobectomy and the right inferior pole parathyroid adenoma was excised. The surgical specimen's histopathological investigation revealed neoplastic parathyroid tissue with lack of reticulin architecture and fibrotic bands, abnormal lack of parafibromin staining indicating an atypical parathyroid adenoma. The postoperative calcium level was 9.7 mg/dL, the phosphorus level was 2.8 mg/dL, and the PTH level was 65.2 ng/L. Conclusion Atypical parathyroid adenoma is very rare and hard to diagnose. Its prognosis is unclear, so regular surveillance is crucial. The patient is closely monitored for recurrence.

PI3K/AKT/mTOR Activation is Associated with Malignant Severity and Poorer Prognosis in Parathyroid Carcinomas.

Parathyroid carcinoma (PCa) is a rare endocrine neoplasm known for its high recurrence. The specific molecular properties influencing the prognosis of PCa remain largely elusive. The present study was designed to explore the significance of PI3K/AKT/mTOR activation in PCa. Over a 10-year period, 64 PCa patients were recruited from dual centers. We analyzed mTORC1 activity in 64 PCa patients and 29 controls, comprising atypical parathyroid tumor (APT), parathyroid adenoma (PAd) and normal parathyroid (PaN) tissues. A panel of selected genes targeting the PI3K/AKT/mTOR pathway (PIK3CA, PTEN, MTOR, TSC1, and TSC2) and CDC73 was performed in 66 available tumor tissues from 64 patients with PCa. Follow-up lasted up to 117 months. There was intertumoral heterogeneity in mTORC1 activity in parathyroid tumors. Notably, we observed significantly elevated mTORC1 activity in PCa patients compared with controls, as assessed by immunohistochemical staining of tissue sections. Further analysis showed that 48.5% of PCa tumors were classified as 'High mTORC1' (above the predefined threshold), while only 22.7% of tumors in the PAd/APT group met this criterion. Additionally, we detected PI3K/AKT/mTOR variants in 16/66 (24.2%) PCa samples, with the majority lacking CDC73 variants. Higher mTORC1 activity was noted in PCa with PI3K/AKT/mTOR variants than in those without. Compared with those without any targeted variants, the PI3K/AKT/mTOR-mut group presented higher levels of serum PTH, ALP and creatinine, and was associated with significantly lower disease-free survival (DFS) and overall survival (OS) (DFS, p < 0.001; OS, p < 0.01). Our findings highlight that the activation of the PI3K/AKT/mTOR pathyway in PCa patients suggests their degree of malignancy, possibly leading to poor outcomes.

Medical therapy of pituitary adenomas

The physiologic experiments of the 1950s and 1960s that established the hypothalamic regulation of pituitary function led to the biochemical characterization of the various release and inhibiting hormones and their receptors over the next two decades and ultimately to the development of medical therapies for the various pituitary adenoma types. The paradigm of medical therapy is the extremely successful use of dopamine agonists (DA) for the treatment of prolactinomas, which built upon the basic knowledge that dopamine is the physiologic prolactin (PRL) inhibitor factor. The discovery of somatostatin and its receptors led to the development of somatostatin receptor ligands (SRLs) for the treatment of acromegaly and thyrotropin (TSH)-secreting adenomas, Knowledge of how growth hormone (GH) interacts with its receptor led to the development of pegvisomant, which blocks the binding of GH to its receptor. Early clinical observations of patients with acromegaly have led to the use of estrogens and selective estrogen receptor modulators to aid in its treatment. DAs and SRLs have only modest activity in Cushing's disease and most therapies involve enzymatic blockade of the various steps in cortisol synthesis, the two most recent being osilodrostat and levoketoconazole. Blockade of the cortisol receptor by mifepristone was found accidentally but then was established as a good treatment for Cushing's syndrome. The finding that clinically nonfunctioning adenomas had dopamine receptors led to the use of DA in these patients as well. Finally, an understanding of some of the abnormal molecular pathways underlying the rare aggressiveness of some adenomas and carcinomas has led to the use of temozolomide and now other chemotherapies and immunotherapies in such patients.

Pituitary adenomas in children: surgical course and functional outcome. Lille cohort retrospective study.

Pituitary Neuroendocrine Tumors are rare in children, but challenging, implying the two purposes to cure the child, and preserve pituitary function. In this paper, we describe our population of children who underwent endoscopic endonasal resection of a pituitary adenoma, in Lille University Hospital. Between 2007 and 2021, all children undergoing EEN surgery for pituitary adenoma were included. Age at surgery, surgical course, type of adenoma, knosp grade and extent of resection were collected. 26 patients were included. 88% were female. All adenomas were functioning. 15 patients had prolactine-secreting adenomas (58%), 9 patients had ACTH-secreting adenomas (35%) and 2 patients had GH-secreting adenomas (8%). Visual disturbance was present at diagnosis in 5 patients. Among them, visual function was improved after surgery in 4 patients and stable in one. Surgical course was always easy. 66% of prolactinomas, all Cushing disease were in remission after surgery. The two patients with acromegaly had to undergo complementary treatment. Follow up was maintained at least 5 years. Surgical treatment remain mainstay in pituitary adenomas. In the pediatric population, surgery can be performed safely and efficiently via en EEN approach.

Prolactinomas

Prolactinomas are the most common type of pituitary adenomas and the most common cause of hyperprolactinemia. There are several pitfalls in the evaluation of hyperprolactinemia, which should be recognized as they affect management decisions. Medical therapy with dopamine agonists is the first-line treatment for prolactinomas. Transsphenoidal surgery is indicated in cases of intolerance or resistance to dopamine agonist therapy.

48-Year clinical experience and genetic analysis of pediatric primary hyperparathyroidism from a single center in China.

This study aims to investigate the clinical and genetic features and change of clinical spectrum of primary hyperparathyroidism (PHPT) in children and adolescents. The clinical and follow-up data of 74 pediatric patients (onset age ≤ 18 years) with PHPT during 1975-2022 were retrospectively analyzed. For comparison, patients were divided into four subgroups according to their time of diagnosis. Genetic analysis was conducted in 40 patients. Pediatric PHPT cases increased largely over time [34 cases (45.9%) in 2015-2022]. The rate of asymptomatic PHPT increased by time (14.7% in 2015-2022 vs. 0% before 2015), in accordance with routine screening of serum calcium becoming a more frequent reason for clinic visit (17.6% in 2015-2022 vs. 0% before 2015). Skeletal manifestation significantly decreased in recent years (64.7% in 2015-2022 vs. 100.0% in 1975-1994, P < 0.05). Sixty-seven patients (90.5%) of the whole cohort underwent parathyroidectomy. Atypical parathyroid adenoma and parathyroid carcinoma occurred in 13.4% and 4.5% of the surgical cases, respectively. Recurrence and persistence of PHPT were observed in 17.9% of postsurgical patients. Germline rare variations (RVs) of PHPT-related genes were found in 42.5% (17/40) of all cases with genetic testing. Compared with no-variation group, the variation group had higher incidence of multiple parathyroid lesions (42.8% vs. 4.3%, P = 0.014), and lower rate of benign lesions and higher rate of recurrence and persistence. Milder cases of Pediatric PHPT are coming to clinical attention probably due to routine lab testing. Genetic testing is recommended for pediatric PHPT patients.

HPB SO50 - A comprehensive review of clinical practice guidelines for managing hepatic adenoma

Abstract Background Hepatic adenoma(HCA) are increasingly diagnosed as incidentalomas. Clinical implications and management vary across and within the different types of Hepatic adenomas. Practice guidelines are needed, because of the many variation, diagnostic tools, and conservative and invasive management protocols. Therefore, our aim was to systematically search for available clinical practice guidelines on hepatic adenoma, critically appraise them, and compare management recommendations. Method Systematic literature search was performed by two investigators using appropriate prespecified search terms within the bibliographic databases of MEDLINE, EMBASE, and PubMed. All HCA guidelines published in peer-reviewed, and English language journals were eligible for inclusion. Clinical practice guidelines on HCA were analysed, compared, and critically appraised using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses recommendations (PRISMA) 2020 checklist. Results The literature search yielded unique 199 papers, 187 were excluded after screening of title/abstract, and 9 after full-text screening. Guidelines included were: (EASL; 2016, (ACG; 2014), (SBH; 2015),). There were no set standards in the assessment methods for grading and gravity of recommendations between guidelines. Observed differences were: (1) indications for biopsy; (2) advices on contraceptive pills and follow-up; (3) use of an lesion centred approach to HCA; (4) lack of adequate treatment recommendations of HCA in male population ; and (5) approach to HCA depending on subtype varaition on magnetic resonance imaging. Conclusion Recognising differences in recommendations can assist in formulating practice standards and identify needs for research.

Somatostatin receptors in pituitary somatotroph adenomas as predictors of response to somatostatin receptor ligands: A pathologist's perspective.

There are five subtypes of somatostatin receptors (SST1-5), which are expressed in several types of solid neoplasms, neuroendocrine tumors, and pituitary adenomas. Most commonly, SST2 and SST5, are of interest regarding diagnostic, treatment, and prognostic purposes. In this article the basic biological characteristics of SST are briefly reviewed, and focus given to the immunohistochemical evaluation of SST2 and SST5 in growth hormone (GH)-secreting pituitary tumors, and their quantification as predictors of response to treatment with somatostatin receptor ligands (SRL), the mainstay of the pharmacological therapy available for these tumors. Although many different scoring systems for SST2 immunohistochemistry showing correlation with SRL response have been reported, among which the immunoreactivity score (IRS) has been the most consistently used, a universally validated immunohistochemical technique and scoring scheme is lacking. Efforts should be made on collaborative multicenter studies aiming at validating homogeneous immunostaining protocols and a scoring system for SST2 and SST5 expression, to help clinicians to define the optimal therapeutic strategy for the patients with somatotroph tumors.

Co-expression of multiple transcription factors is associated with clinical features and endocrine prognosis in growth hormone-secreting pituitary adenomas.

The types of growth hormone-secreting pituitary adenomas are diverse, we have found that there are significant differences in clinical features and prognosis between PIT-1 single-cell spectrum growth hormone adenomas and growth hormone phenotypic polyhormonal adenomas. This study examined a cohort of 193 patients with growth hormone-secreting pituitary adenoma (GHPA), stratifying them into two groups: PIT-1 single transcription factor positive growth hormone adenoma (STF-GHPA) and Multiple transcription factor-positive growth hormone-secreting adenomas (MTF-GHPA). The objective was to compare these two groups' clinical characteristics. Within the MTF-GHPA group, we further subtyped them based on transcription factors to evaluate potential variations in clinical manifestations. Logistic regression analyses were employed to develop a risk factor model for investigating factors influencing hormone remission. There were no statistically significant differences in terms of age, gender, serum GH, and IGF-1 levels between patients diagnosed with MTF-GHPA and STF-GHPA. However, patients with MTF-GHPA exhibited a higher proportion of hypopituitarism compared to those with STF-GHPA. Furthermore, MTF-GHPA were characterized by smaller tumor size and less invasiveness, as indicated by lower Knosp classes. However, patients with MTF-GHPA have a lower rate of hormonal remission (30.8%) and more postoperative complications (31.0%), which means that STF-GHPA (hormonal remission:71.6%; postoperative complications:13.4%) has a better endocrine outcome than MTF-GHPA patients. Between the PIT-1 + SF-1+ and PIT-1 + TPIT+ subtypes within MTF-GHPA, significant differences were also observed in tumor size, endocrine outcomes, and postoperative complications. Risk factors influencing hormonal remission for GHPA included preoperative GH level, primary/recurrent, extent of resection, and transcription factor expression. Co-expression of multiple transcription factors is an important factor associated with clinical behavior and endocrine outcomes in patients with GHPA.

Elucidating Clinical Queries for Tailored Therapy in Patients with Prolactinoma.

Prolactinomas are the most prevalent type of pituitary neuroendocrine adenomas, primarily affecting women of reproductive age. Unlike other pituitary tumors, the first-line management has traditionally been pharmacological rather than surgical. This preference is due to the effectiveness of dopamine agonists (DAs), which typically reduce tumor size and normalize prolactin levels in most patients. However, this does not imply that there is no room for improvement; the duration of treatment and medication side effects often lead to compliance issues among patients. Recent advances in surgical techniques and molecular biology have paved the way for the development of precision medicine, allowing for more flexible and personalized treatment strategies for prolactinomas. This review aims to enhance clinical decision-making and patient care for endocrinologists by focusing on several key factors: predictive markers of DA sensitivity, clinical characteristics and suitability for transsphenoidal adenomectomy as a potential first-line treatment, factors determining the successful withdrawal of DAs after prolonged use, safety concerns during pre/post-pregnancy and breastfeeding, and determinants of tumor aggressiveness. Through tailored therapy-a patient-focused, multidisciplinary approach- we aim to improve the management of prolactinoma patients.

Long term outcomes of pituitary adenomas in Multiple Endocrine Neoplasia type 1: a nationwide study.

Historically, Multiple Endocrine Neoplasia type 1 (MEN1)-related pituitary adenomas (PAs) were considered more aggressive and treatment-resistant than sporadic PAs. However, recent studies suggest similarities in their behavior. This study aimed to evaluate the long-term outcomes of MEN1 PAs and identify predictive factors. Nationwide multicenter retrospective cohort study of MEN1-related PAs with a minimum 1-year follow-up, collecting patient demographics, germline MEN1 pathogenic variants (PV), PA size, secretory profile, radiological characteristics, treatments, and outcomes. We analyzed 84 PAs, 69%in females and 31% in males (P<0.001), diagnosed at a mean age of 35.2±14.9 years, mostly through screening (60.7%). Median follow-up was 9 years (IQR:4-16). Prolactin-secreting PAs (PRLomas) (53.5%) and microadenomas (65.5%) were most common. Dopamine agonist treatment was first line for 16 macroPRLomas and 25 microPRLomas, 60.9% of them achieved PRL normalization. There was no significant association observed with tumor size, sex, treatment duration or MEN1 PV. The risk of progression from micro-PA to invasive macro-PA was 7.2% (4/55), after 8 years (IQR:4-13), all of them were microPRLomas. Kaplan-Meier estimation curve showed significantly higher progression probability in microPRLomas than in other microadenomas subtypes (P=0.017) or microNFPAs (P=0.032). No differences were found between sex, age, or germline MEN1 PV. MEN1-related micro-PAs have a low risk of progressing to invasive macro-PAs, regardless of sex, age at diagnosis, or MEN1 germline PV. The risk is higher for microPRLomas over the long term. Therefore, long-term surveillance with reduced frequency, rather than intensive short-term monitoring, may be appropriate for patients with MEN1-related PAs.

7254 An Unusual Case Of Hypercalcemia

Abstract Disclosure: S. Shushtarian: None. M. Balogun: None. T. Kaur: None. Hypercalcemia varies depending on severity. Higher serum calcium levels and more severe symptoms may indicate primary hyperparathyroidism or a malignant cancer. This is a case of a 32 year old female who presented with recurrent history of nephrolithiasis, found to have hypercalcemia of 13.4 mg/dL and parathyroid hormone of 1928.9 pg/mL, with phosphorus of 1.5 mg/dL. Ultrasound of her thyroid revealed a complex nodule arising from the right parathyroid gland measuring 2.2 X 2.0 cm. CT chest revealed diffuse osseous sclerosis secondary to metabolic disorder. Sestamibi scan did not localize any parathyroid adenoma. MRI of the thoracic and lumbar spine showed multiple small enhancing lesions throughout the pelvis and in the left rib, likely brown tumors related to hyperparathyroidism. X-ray of bony prominence on the patient’s left knee revealed a large lytic lesion of the proximal tibial diaphysis measuring 5.1 X 1.9 cm, concerning for aggressive neoplasm. Subsequent left tibial bone biopsy revealed giant cell rich lesions consistent with brown tumor of hyperparathyroidism. Due to our patient’s high calcium levels and large nodule size, she was referred to a tertiary center as the concern for parathyroid carcinoma and post-op hungry bone syndrome was high. Pre-op PTH level was 1408 pg/mL and post-op PTH was 96 pg/mL. The tumor removed was 2.1 cm. Post surgical pathology was consistent with atypical parathyroid adenoma. Patient was referred for genetic testing. An atypical parathyroid adenoma (APA) only accounts for 1.2 to 1.3% of cases of primary hyperparathyroidism. 80-85% of primary hyperparathyroidism is due to typical adenoma, and 10 to 15% of cases are due to hyperplasia or multiple gland disease. APA can often be confused with parathyroid carcinoma (PC), as they both have a 1:1 male to female ratio, high serum calcium levels, symptomatic hypercalcemia, high PTH levels, and fragility fractures. There are studies showing that both APA and PC have loss of nuclear parafibromin immunoreactivity. In addition, neither APA nor PC have any correlation with menopause, hormones, or gene deletions, unlike typical adenomas. Biopsy is necessary for diagnosis as the histological and immunohistochemical differences can differentiate APA vs PC. Histological features include pseudo-capsular invasion, bands of fibrosis, pronounced trabecular growth, nuclear atypia, and prominent nucleoli. Also, APA has a strong membranous staining pattern of E-cadherin, whereas PC has a loss of membranous staining. These differences are essential as although APA and PC clinically present similarly, APA lacks the invasive growth and possibility for metastatic disease that PC has. The likelihood for relapse of APA is low. Presence of malignancy criteria are indicative that a mass is actually PC and not APA. Despite this, APA is still considered a tumor of uncertain malignant potential and requires follow up. Presentation: 6/3/2024

7508 Primary Hyperparathyroidism Caused By A CDC73-related Atypical Parathyroid Tumor

Abstract Disclosure: R. Cardenas: None. S. Tariq: None. R. Habibi: None. N. Ebrahimi: None. E. Astiazaran-Symonds: None. Background: Primary hyperparathyroidism (PHPT) is a common endocrine disease, causes include: parathyroid adenomas (80-85%), parathyroid hyperplasia (10-15%), atypical parathyroid adenomas (APA) (1.2 %) and parathyroid carcinomas (PC) (1%). APA share many anatomic and histopathologic features with PC making the distinction between the two challenging. Although most are sporadic, some APA are caused by germline mutations in the CDC73 gene, which is associated with hyperparathyroidism-jaw tumor (HPT-JT) syndrome PC and familial isolated PHPT with APA. Clinical Case: A 42-year-old female presented to the clinic for evaluation of recurrent PHPT. She was diagnosed at age 22 when she experienced fatigue, polydipsia with hypercalcemia (12.9mg/dl). She underwent superior bilateral parathyroidectomy with pathology consistent with parathyroid adenoma. Twenty years later, symptoms recurred and tests showed hypercalcemia (13.0 mg/dl), elevated PTH (252 pg/dl), kidney function preserved (GFR: 82.5 ml/min), normal vitamin D 25 OH (31 ng/dl). Patient denied history of nephrolithiasis or fractures. Family history was positive for kidney stones in father and siblings, also history of a jaw tumor in niece. Sestamibi scan showed a left inferior parathyroid adenoma. Patient underwent resection of the adenoma; pathology revealed a left parathyroid adenoma with atypical parathyroid tumor, &amp;gt;95% cellularity with cytologic features concerning for malignancy, prominent macronucleoli, necrosis, elevated mitotic activity and Ki67 with 15% tumor cells without vascular invasion. Post-op Calcium and PTH normalized (9.6 mg/dl and 10.8 pg/ml, respectively). Genetic testing via multi-gene panel identified a whole gene deletion of CDC73, consistent with hyperparathyroidism-jaw tumor syndrome. Panoramic jaw x-rays did not show jaw tumors. Genetic testing for family members is underway. Conclusion: Although somatic mutations in CDC73 are frequently found in sporadic APA and PC, germline mutations are a rare cause of PHPT associated with these tumors. Histopathological examination is necessary to confirm the diagnosis of APA and to differentiate it from PC, which has a recurrence rate &amp;gt;50%. APA should be treated as a “tumor of uncertain malignant potential” and needs to be carefully and periodically followed up with measurement of Ca, PTH and vitamin D. Confirmation of a CDC73 mutation by genetic testing helped identify the increased risk for other associated tumors in jaw, kidneys and uterus prompting initiation of surveillance with panoramic jaw x-rays with neck shielding, renal US and pelvis US. Genetic testing of family members will allow timely detection and treatment of individuals at risk. Presentation: 6/3/2024

7330 Acute Hypercalcemic Renal Failure As A Presenting Manifestation Of Primary Hyperparathyroidism Due To Atypical Adenoma

7330 Acute Hypercalcemic Renal Failure As A Presenting Manifestation Of Primary Hyperparathyroidism Due To Atypical Adenoma

Diagnosis and management of pituitary adenomas in children and adolescents.

Pituitary adenomas (PAs)-also now called pituitary neuroendocrine tumours or Pit-NETS-are rare in children and adolescents and exceptional below the age of 10. Most evidence-based high-quality data are derived from larger studies in adult patients. We will review recent knowledge on the epidemiology, clinical features, diagnosis, and treatment modalities of the different types of pituitary adenomas diagnosed in children and adolescents, emphasizing the many reasons why these cases should be discussed within pituitary-specific multidisciplinary teams with experts from both paediatric and adult practice. Paediatric PA presents multiple peculiarities that may challenge their adequate management. They are overall proportionally larger and more aggressive than in adults, with potential mass effects including hypopituitarism. Hormonal hypersecretion is frequent, resulting in clinical syndromes affecting normal growth and pubertal development. Prolactinomas represent the most frequent subtype of PA found during childhood, followed by adrenocorticotropin (ACTH) and growth hormone (GH)-secreting adenomas, while clinically non-functioning adenomas are exceptionally diagnosed before the age of 16. The occurrence of a pituitary tumour in a young individual should also prompt genetic testing in each case, searching for either germline mutations in one of the known genes that may drive inherited/familial PA (such as the multiple endocrine neoplasia type 1 or MEN1 gene, or the aryl hydrocarbon receptor interacting protein or AIP gene), or for a mosaic activating mutation of GNAS as found in the McCune-Albright syndrome.

Drug induced hypoprolactinemia.

Prolactin levels can be influenced by multiple medications primarily through the interaction with dopamine receptors which regulate its secretion. Unlike hyperprolactinemia which has a well-defined clinical phenotype, the effects of hypoprolactinemia beyond inability to lactate are incompletely understood. Recent studies have raised concerns regarding detrimental changes in glucose metabolism, sexual function and psychological profile in patients with low prolactin levels. In contrast with anatomic and genetic etiologies, drug-induced hypoprolactinemia is usually reversible after dose reduction of the offending medication. The most common clinical scenario of drug-induced hypoprolactinemia in the endocrine clinic pertains to patients treated with cabergoline or bromocriptine for prolactin-secreting or other types of pituitary adenomas. Also, data has accumulated regarding hypoprolactinemia in patients receiving aripiprazole for schizophrenia and other psychiatric disorders. These patients warrant careful evaluation for comorbidities. This review aims to increase awareness about the potentially detrimental effects of drug-induced hypoprolactinemia, which should be considered in clinical practice decisions.

The 2022 WHO classification of tumors of the pituitary gland: An update on aggressive and metastatic pituitary neuroendocrine tumors.

The vast majority of pituitary neuroendocrine tumors (PitNETs) are benign and slow growing with a low relapse rate over many years after surgical resection. However, about 40% are locally invasive and may not be surgically cured, and about one percentage demonstrate an aggressive clinical behavior. Exceptionally, these aggressive tumors may metastasize outside the sellar region to the central nervous system and/or systemically. The 2017 (4th Edition) WHO Classification of Pituitary Tumors abandoned the terminology "atypical adenoma" for tumors previously considered to have potential for a more aggressive behavior since its prognostic value was not established. The 2022 (5th Edition) WHO Classification of the Pituitary Tumors emphasizes the concept that morphological features distinguish indolent tumors from locally aggressive ones, however, the proposed histological subtypes are not consistent with the real life clinical characteristics of patients with aggressive tumors/carcinomas. So far, no single clinical, radiological or histological parameter can determine the risk of growth or malignant progression. Novel promising molecular prognostic markers, such as mutations in ATRX, TP53, SF3B1, and epigenetic DNA modifications, will need to be verified in larger tumor cohorts. In this review, we provide a critical analysis of the WHO guidelines for prognostic stratification and diagnosis of aggressive and metastatic PitNETs. In addition, we discuss the new WHO recommendations for changing ICD-O and ICD-11 codes for PitNET tumor behavior from a neoplasm either "benign" or "unspecified, borderline, or uncertain behavior" to "malignant" neoplasm regardless of the clinical presentation, histopathological subtype, and tumor location. We encourage multidisciplinary initiatives for integrated clinical, histological and molecular classification, which would enable early recognition of these challenging tumors and initiation of more appropriate and aggressive treatments, ultimately improving the outcome.

A National Cancer Database Analysis of the Characteristics and Outcome of Colon Cancer According to Type of Preexisting Adenoma

BackgroundThe vast majority of colon cancers occur in pre-existing adenomas. Little is known about the impact of adenoma type on behavior and outcome of subsequent carcinomas. The present study aimed to assess characteristics, behavior, and outcome of colon adenocarcinoma based on histologic type of pre-existing adenoma. MethodsUS-National Cancer Database was searched between 2005 and 2019 for patients with colonic adenocarcinoma with known adenoma type who underwent colectomy. Patients were divided into 3 groups according to type of adenoma in which carcinoma developed: tubular adenoma (TA), villous adenoma (VA), and tubulovillous adenoma (TVA)-associated carcinomas. The main outcome of the study was 5-year overall survival (OS). Results66,854 patients were included. 79.3% of carcinomas originated from TVA, 10.2% from VA, and 0.5% from TA. Patients with adenocarcinoma in VA were more often female whereas carcinomas in TA affected patients of Asian race more often. Approximately one-third of carcinomas in villous and tubulovillous adenomas were in the cecum whereas one-third of carcinomas in tubular adenomas were in the sigmoid colon. More TA-associated carcinomas were of clinical T1-2 stage (30.2% vs. 20.8%; P < .001), clinical N0 stage (69% vs. 62.2%, P < .001), and high grade (15.9% vs. 11.5%, P < .001) compared to VA-associated carcinomas. Patients with TA-associated carcinomas had longer mean OS than patients with VA and TVA-associated carcinomas (130.1 vs. 116.9 vs. 123.5 months, P < .0001). ConclusionsAdenocarcinomas that arose in TA had more T1-2 stage and N0 stage, higher grade, and longer OS than did adenocarcinomas that arose in VA and TVA.

Early identification of postoperative remission for thyrotropin-secreting adenomas.

Thyrotropin-secreting adenoma (TSHoma) is a rare type of pituitary adenoma, occurring in one per million people. Little is known about TSHoma. We summarized the demographic, clinical and hormonal characteristics of TSHoma based on a single-centre experience. Moreover, we explored the predictive value of postoperative thyroid function for long-term remission. We retrospectively analysed 63 patients who were diagnosed as TSHoma and surgically treated at our hospital from January 2015 to June 2021. The preoperative clinical characteristics were analysed and compared between remission and nonremission groups. Thyroid function was measured at 1 day, 1 month, 3 months, 6 months, 12 months and over 12 months after surgery to determine whether they could predict long-term remission. The male to female ratio for TSHoma was 1.25. The mean age at diagnosis was 45 ± 12 years. Clinical presentation was varied, presenting with hyperthyroidism (68.25%), space-occupying effect (15.87%), amenorrhea (7.14% of female patients) and nonsymptoms (22.22%). 88.14% of patients achieved postoperative endocrinological remission. Larger tumour size and tumour invasion into cavernous sinus and suprasellar with chiasmal compression were strong predictors of lower rates of endocrinological remission. Postoperative thyroid function at 3 months was a viable diagnostic predictor for postoperative remission, especially for FT4 level with a 20.65 pmol/L cutoff. Tumour size and extent are major prognostic factors for remission. Postoperative thyroid function at 3 months could be used as a clinical prediction tool for long-term endocrinological remission.

Severe Hypercalcemia as Presentation of Atypical Cystic Parathyroid Adenoma: A Case Report

Severe Hypercalcemia as Presentation of Atypical Cystic Parathyroid Adenoma: A Case Report