scholarly journals Genetic Alteration Profiles and Clinicopathological Associations in Atypical Parathyroid Adenoma

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Xinxin Mao ◽  
Yan Wu ◽  
Shuangni Yu ◽  
Jie Chen
Keyword(s):  
Parathyroid Adenoma ◽  
De Novo ◽  
Sequencing Analysis ◽  
Sequencing Data ◽  
Genomic Alterations ◽  
Parathyroid Tumors ◽  
Formalin Fixed Paraffin ◽  
Parathyroid Adenomas ◽  
Formalin Fixed Paraffin Embedded ◽  
Atypical Parathyroid Adenoma

Genomic aberrations associated with atypical parathyroid adenoma (AA) are poorly understood. Thus, herein, we sought to expand our current understanding of the molecular basis of atypical parathyroid adenomas. We analyzed 134 samples that had been surgically obtained from parathyroid tumors, including parathyroid carcinomas, atypical parathyroid adenomas, and parathyroid adenomas. The tumors were harvested from formalin-fixed, paraffin-embedded tissues. Fifteen tumor-related genes from recently published genome sequencing data were subjected to targeted sequencing analysis, and an average sequencing depth of 500x was achieved. Sixteen (16/50, 32%) AA tumors harbored at least one of the following genomic alterations: CDC73 (12, 24%), EZH2 (4, 8%), HIC1 (1, 2%), and CDKN2A (1, 2%). Our study identified, for the first time, a relatively high frequency of genomic alterations in patients with AA in a Chinese population. This suggests that AA arises de novo, rather than developing from a parathyroid adenoma. Altogether, these findings will improve our understanding of the malignant potential of parathyroid tumors at the molecular level.

Sequencing Analysis and Phylogenetic Tree of HPV Isolated from Breast Cancer Patients at Thi-Qar Province/Iraq

2020 ◽  
pp. 37-40
Keyword(s):  
Nucleotide Sequence ◽  
Phylogenetic Tree ◽  
Evolutionary Relationship ◽  
Nucleotide Sequencing ◽  
Sequencing Analysis ◽  
Breast Cancer Patients ◽  
The North ◽  
Formalin Fixed Paraffin ◽  
Formalin Fixed Paraffin Embedded ◽  
History Of

Genetic variety examination has demonstrated fundamental to the understanding of the epidemiological and developmental history of Papillomavirus (HPV), for the development of accurate diagnostic tests and for efficient vaccine design. The HPV nucleotide diversity has been investigated widely among high-risk HPV types. To make the nucleotide sequence of HPV and do the virus database in Thi-Qar province, and compare sequences of our isolates with previously described isolates from around the world and then draw its phylogenetic tree, this study done. A total of 6 breast formalin-fixed paraffin-embedded (FFPE) of the female patients were included in the study, divided as 4 FFPE malignant tumor and 2 FFPE of benign tumor. The PCR technique was implemented to detect the presence of HPV in breast tissue, and the real-time PCR used to determinant HPV genotypes, then determined a complete nucleotide sequence of HPV of L1 capsid gene, and draw its phylogenetic tree. The nucleotide sequencing finding detects a number of substitution mutation (SNPs) in (L1) gene, which have not been designated before, were identified once in this study population, and revealed that the HPV16 strains have the evolutionary relationship with the South African race, while, the HPV33 and HPV6 showing the evolutionary association with the North American and East Asian race, respectively.

Do patients with atypical parathyroid adenoma need a close follow-up?

2021 ◽  
Author(s):  
Federica Saponaro ◽  
Elena Pardi ◽  
Laura Mazoni ◽  
Simona Borsari ◽  
Liborio Torregrossa ◽  
...  
Keyword(s):  
Parathyroid Adenoma ◽  
Serum Calcium ◽  
Good Prognosis ◽  
Histopathological Diagnosis ◽  
Symptomatic Disease ◽  
Asymptomatic Patients ◽  
Parathyroid Adenomas ◽  
Relevant Role ◽  
Atypical Parathyroid Adenoma

Abstract Context Atypical parathyroid adenomas (APAs) are neoplasms with uncertain malignant potential but lack unequivocal histological signs of malignancy. Objective To retrospectively evaluate the clinical and biochemical profiles of patients with APA, the outcome after parathyroidectomy (PTX), and the presence of CDC73 germline and somatic mutations. Design Monocentric study on consecutive patients undergoing PTX for primary hyperparathyroidism (PHPT) between June 2000 and December 2020. Patients Fifty-eight patients with a confirmed histopathological diagnosis of APA. Age and sex-matched controls with parathyroid adenoma (PA) were also included. Results Fifty-four patients had sporadic PHPT and four familial isolated hyperparathyroidism (FIHP). Thirty-four patients (59%) had a symptomatic disease. Serum calcium and PTH levels were significantly higher in symptomatic compared to asymptomatic patients (P=0.048 and 0.008, respectively). FIHP patients were younger than the sporadic counterpart (30±17yr vs. 55±13 yrs). APA patients had significantly higher serum calcium and PTH levels and lower 25(OH)D concentration, BMD and T-score at 1/3 distal radius compared to those with PA. Four of 56 APA patients displayed a CDC73 germline mutation. No somatic CDC73 mutation was identified in 24 tumor specimens. The mean follow-up after surgery was of 60±56.4 months. All but six patients (90%), five with apparently sporadic PHPT and one with FIHP, were cured after surgery. Conclusions The large majority of patients with APA, despite a moderate/severe phenotype, have a good prognosis. Germline CDC73 mutation-positive patients had a higher rate of persistent/recurrent disease. CDC73 gene alterations do not seem to have a relevant role in the tumorigenesis of sporadic APA.

Frequency of actionable genomic alterations in early-stage lung adenocarcinoma (LA) detected by next-generation sequencing (NGS).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e17541-e17541
Author(s):  
Kai Wang ◽  
Philip Stephens ◽  
Roman Yelensky ◽  
Jeffrey S. Ross ◽  
Vincent A. Miller ◽  
...  
Keyword(s):  
Early Stage ◽  
Mtor Inhibitors ◽  
Driver Mutations ◽  
Tumor Type ◽  
Genomic Alterations ◽  
Genomic Libraries ◽  
Formalin Fixed Paraffin ◽  
Formalin Fixed Paraffin Embedded ◽  
Ffpe Tissues ◽  
Risk Patients

e17541 Background: Early stage LA (≤T1N0) has a variable natural history. Although many patients are cured (~2/3) with surgery, many tumors recur and better methods are needed to distinguish these subsets and tailor therapy accordingly. We undertook a pilot study of NGS in such tumors to characterize the frequency and diversity of actionable genomic alterations in this setting. Methods: Formalin-fixed paraffin embedded (FFPE) tissues from 21 archival samples collected from 2007 to 2011 were obtained commercially with accompanying clinical and pathologic data. Clinical characteristics: female (17)/male (4); T1N0 (18), AIS (2), MIA (1). Pathologic LA subtype: acinar (n=8), mucinous (n=4), lepidic (n=4), and mixed (n=2) in addition to AIS (n=2) and MIA (n=1). Targeted NGS performed in a CLIA laboratory (Foundation Medicine) gave evaluable results in all cases. Genomic libraries were captured for 3230 exons in 182 cancer-related genes plus 37 introns from 14 genes often rearranged in cancer and sequenced to average median depth of 640X with 99% of bases covered >100X. Results: Forty-one driver mutations were identified in 17 genes among the 21 patients (avg= 1.9) including 28 base substitutions, 5 indels, 4 amplifications, 3 homozygous deletions and 1 rearrangement. Notably, 90% of cases (19/21) harbored at least one alteration that can be classified as actionable-linked to an approved therapy in LA or another tumor type or a clinical trial. Examples include alterations in EGFR (n=6), NF1 (n=2, PI3K/mTOR inhibitors), CDNK2A (n=1, CDK inhibitors), EML4-ALK (fusion, n=1, ALK inhibitor), ERBB2 (n=1, TKI inhibitors), STK11 (n=1, mTOR inhibitors), and MDM2 (n=1, nutlins). Conclusions: NGSidentified drivergenomic alterations in T1N0 LA, MIA and AIS. On average, two known driver mutations were identified per tumor, many of which are associated with existing or emerging targeted therapies. This provides rationale for future investigation of larger series of T1N0 LA, AIS and MIA, using NGS to evaluate the prognostic value of these changes and could presage adjuvant trials in higher risk patients.

scholarly journals Clinical Behaviors of Atypical Parathyroid Adenomas

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A258-A259
Author(s):  
Sarah S Pearlstein ◽  
Kim Eric ◽  
Chomsky-Higgins Kate ◽  
Elham Khanafshar ◽  
Quan-Yang Duh
Keyword(s):  
Parathyroid Adenoma ◽  
Disease Recurrence ◽  
Neck Mass ◽  
Recurrence Rates ◽  
Parathyroid Adenomas ◽  
Long Term Follow Up ◽  
Biochemical Cure ◽  
Atypical Parathyroid Adenoma

Abstract Background: Atypical parathyroid adenoma is a rare entity that share some pathology features of parathyroid carcinoma such as fibrosis. Little is known about the clinical behavior of atypical parathyroid adenomas. Pathologically, it is defined as a hypercellular parathyroid lesion with intratumoral banding fibrosis, mitotic figures, trabecular growth and presence of tumor in the surrounding capsule but lacks unequivocal evidence of invasion, such as invasion to peritumoral vessels, perineural invasion and surrounding structures. Methods: A retrospective study of 15 consecutive patients with atypical parathyroid adenoma treated at a single center between 2010 and 2020 was performed. Patient demographics, clinical characteristics, biochemical profile, indications for surgery, preoperative localization studies, intraoperative findings, histopathological characteristics, disease recurrence or persistence and survival were collected. Results: 7 of 15 were female with a median age of 62 (IQR: 52–67). Five of the 15 patients (33%) were re-operative. No patients presented with palpable neck mass. Presentations were consistent with usual primary hyperparathyroidism. Average calcium on presentation was 11.2, and average PTH was 199. One patient had known MEN1 syndrome and one patient had family history of hyperparathyroidism but had negative genetic testing. Most patients 12/15 had correctly localizing imaging pre-operatively with the other 3 having equivocal or non-localizing studies. Two patients did not have biochemical resolution of hyperparathyroidism, both were re-operative. Of the patients with biochemical cure, 6 did not have follow up beyond 6 months, and 7 patients had long term follow up with persistent biochemical resolution and no recurrence of disease for a median of 4 years (IQR: 3.75–9.25). On review of pathology, no patients had invasive features and all patients had presence of thick fibrous bands or capsule. Conclusion: Patients with atypical adenoma have good response to surgery and low recurrence rates. Reoperation with associated scarring and fibrous bands can confound pathological findings. Our experience shows that patients found to have atypical parathyroid adenoma at their primary operation with resulting biochemical cure can be followed long-term with seemingly indolent and nonaggressive behavior.

Multiple concurrent atypical parathyroid adenomas: a rare occurrence

2020 ◽  
Vol 13 (5) ◽  
pp. e234421
Author(s):  
Jack Faulkner ◽  
Kiran Varadharajan ◽  
Natasha Choudhury
Keyword(s):  
Parathyroid Adenoma ◽  
Vascular Invasion ◽  
Parathyroid Carcinoma ◽  
Postoperative Recovery ◽  
Rare Entity ◽  
Rare Occurrence ◽  
First Case ◽  
Parathyroid Adenomas ◽  
Atypical Parathyroid Adenoma ◽  
Histological Characteristics

We present a case of an 80-year-old patient with three concurrent multiple atypical parathyroid adenomas. The patient was managed with bilateral parathyroid exploration and concurrent parathyroidectomy. Postoperative recovery was uneventful. Atypical parathyroid adenomas are a rare entity that are clinically difficult to distinguish from parathyroid carcinoma. Histological characteristics are similar however atypical adenomas lack complete capsular or vascular invasion and cannot be considered malignant. All reported cases of atypical parathyroid adenoma are solitary lesions. We present the first case of multiple concurrent atypical parathyroid adenomas.

scholarly journals An Interesting Case of Life-Threatening Hypercalcemia Secondary to Atypical Parathyroid Adenoma versus Parathyroid Carcinoma

2014 ◽  
Vol 2014 ◽  
pp. 1-4 ◽  
Author(s):  
Ankur Mishra ◽  
David Newman
Keyword(s):  
Parathyroid Adenoma ◽  
Serum Calcium ◽  
Parathyroid Carcinoma ◽  
Interesting Case ◽  
High Serum ◽  
En Bloc ◽  
Severe Hypercalcemia ◽  
Parathyroid Adenomas ◽  
Life Threatening ◽  
Atypical Parathyroid Adenoma

Context.Severe hypercalcemia is a life-threatening condition. Atypical parathyroid adenoma and parathyroid carcinomas are uncommon causes which can be difficult to differentiate.Objective.We report a case of a 36-year-old male with very high serum calcium due to a possible atypical parathyroid adenoma versus parathyroid carcinoma.Case Illustration.A serum calcium level of 23.2 mg/dl was noted on admission. He was initially treated with IV hydration, pamidronate, and salmon calcitonin to lower his calcium levels. He also underwent a surgical en bloc resection of parathyroid mass. Pathology showed a mixed picture consistent with possible atypical adenoma versus parathyroid carcinoma. However, due to the possible involvement of the recurrent laryngeal nerve, parathyroid carcinoma was more likely. Also after operation the patient developed hungry bones syndrome and his calcium was replaced vigorously. He continues to be on calcium, vitamin D, and calcitriol supplementation.Results.A review of the literature was conducted to identify previous studies pertaining to parathyroid adenomas and parathyroid cancer.Conclusion.We thereby conclude that hypercalcemia requires very careful monitoring especially after operation. Also it can be very difficult to distinguish between atypical parathyroid adenomas and parathyroid carcinomas as in our case and no clear cut guidelines yet exist to differentiate the two based on histology.

scholarly journals Atypical Parathyroid Adenoma in a Young Man

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A182-A182
Author(s):  
Elizabeth R Bowen ◽  
Joseph Stephen Dillon
Keyword(s):  
Parathyroid Hormone ◽  
Parathyroid Adenoma ◽  
Mitotic Activity ◽  
Parathyroid Carcinoma ◽  
Sudden Onset ◽  
Lytic Lesion ◽  
Brown Tumor ◽  
Adjacent Structures ◽  
Parathyroid Adenomas ◽  
Atypical Parathyroid Adenoma

Abstract Patient is a 38-year-old man who developed sudden onset of pain in the upper left arm while carrying a case of water. The pain recurred periodically over the next few months. He presented to the emergency department where imaging showed a pathologic fracture in the proximal left humerus through a lytic lesion. Laboratory testing showed: calcium 13.8 mg/dL (8.5–10.1 mg/dL), 25-OH vitamin D 8 ng/mL (31–100 ng/mL), parathyroid hormone 1583.1 pg/mL (18.5–88 pg/mL). Neck ultrasound showed a complex nodule in the left neck measuring 4.2 x 1.7 x 2.5 cm. Subsequent biopsy of the left arm lesion showed a Brown tumor. The patient was referred to endocrinology. There was concern for parathyroid carcinoma given the elevated parathyroid hormone and large neck lesion. Technetium-99m sestamibi scan showed a 4.1 x 2.6 x 2.5 cm mass posterior to the left thyroid lobe. He subsequently underwent left hemithyroidectomy and parathyroidectomy. Pathology revealed a 3.1 cm parathyroid mass with scattered fibrous bands, foci of prominent nucleoli and foci of sheet-like trabecular and spindled architecture. It was without necrosis, lymphovascular invasion, perineural invasion, increased mitotic activity, atypical mitoses or invasion into adjacent structures. Thus, it was classified as an atypical parathyroid adenoma. Primary hyperparathyroidism is the third most common endocrine disorder, but fewer than 2% occur as a result of an atypical parathyroid adenoma. Patients with an atypical parathyroid adenoma tend to have a more dramatic clinical presentation compared to those with classic adenoma. We see higher calcium and parathyroid hormone levels. Atypical parathyroid adenomas are classified as such due to other features which place the lesion at a higher risk for malignant behavior including higher mitotic activity, adherence to adjacent structures, banding fibrosis and a growth pattern that is either solid or trabecular. In contrast to parathyroid carcinoma, atypical parathyroid adenomas do not show invasion into the surrounding tissues or lymphatic/vascular vessels, and there should be no evidence of metastatic disease. The exact definition of an atypical parathyroid adenoma varies among institutions, and recognition of the defining features (or lack thereof) necessitates an experienced endocrine pathologist. Due to their uncertain malignant potential, patients with an atypical parathyroid adenoma should undergo routine surveillance for recurrence. Routine follow-up of calcium, parathyroid hormone and imaging is indicated to detect for recurrence. A CDC73 germline mutation is associated with recurrence compared to CDC73-negative patients. Parafibromin expression is also thought to play a role although studies so far have had discrepant results.

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