Hot Trends in Pheochromocytoma and Paraganglioma: Are We Getting Closer to Personalized Dynamic Prognostication?

Pheochromocytoma and abdominal paraganglioma (PPGL) are rare catecholamine-producing, keratin-negative, non-epithelial neuroendocrine neoplasms characterized by a unique association with syndromic diseases caused by constitutional mutations in a wide range of susceptibility genes. While PPGLs are recognized for their malignant potential, the risk of metastatic disease varies depending on several clinical, histological, and genetic factors. Accurate diagnosis and prognosis of these tumors require a multidisciplinary approach, integrating insights from various medical specialties. Pathologists play a crucial role in this complex task, as numerous morphological, immunohistochemical, and genetic findings can be linked to worse outcomes. Therefore, it is vital to stay informed about the latest advancements in PPGL pathology. This brief review provides an overview of the challenges associated with PPGLs and highlights the most recent developments in tumor prognostication

Is there a relationship between age and side dominance of tubal ectopic pregnancies? – A preliminary report

Objectives: To determine whether there exists a relationship between age and side dominance of tubal ectopic pregnancies. Material and Methods: One hundred twenty patients were retrospectively analyzed. The sides of the tubal ectopic pregnancies were recorded on the basis of laparoscopy or laparotomy findings. Five age groups were created: 20-24, 25-29, 30-34, 35-39, and ≥40 years. Results: Of the patients who were ≥ 30 years of age, 46 (69%) and 21 (31%) had tubal ectopic pregnancies on the right and left sides, respectively (p=0.002). In the 35-39 years of age group, 17 of 20 patients (85%) had tubal ectopic pregnancies on the right, and 3 of 20 patients (15%) on the left side (p=0.002). In the 30-34 years of age group, 26 of 39 patients (67%) and 13 of 39 patients (33%) had tubal ectopic pregnancies on the right and left sides, respectively (p=0.037). In the ≥ 40 years of age group, 3 of 8 patients (37%) had tubal ectopic pregnancy on the right side, while 5 patients (63%) on the left side (p=0.48). Conclusions: Patients who are between the age of 30-40 years have a right-sided dominance of tubal ectopic pregnancy, however studies that involve larger numbers of subjects are needed to make definitive conclusions about women older than 40 years of age

Ocena łożyska całkowicie przodującego przy pomocy rezonansu magnetycznego i ultrasonografii w celu wykrycia łożyska wrośniętego i jego wariantów

Objective: To evaluate the importance of ultrasonography (US) and magnetic resonance imaging (MRI) in detecting placental adherence defects. Material and methods: Patients diagnozed with total placenta previa (n=40) in whom hysterectomy was performed due to placental adherence defects (n=20) or in whom the placenta detached spontaneously after a Cesarean delivery (n=20) were included into the study between June 2008 and January 2011, at the Department of Obstetrics and Gynecology, Ege University (Izmir, Turkey). Gray-scale US was used to check for any placental lacunae, sub-placental sonolucent spaces or a placental mass invading the vesicouterine plane and bladder. Intra-placental lacunar turbulent blood flow and an increase in vascularization in the vesicouterine plane were evaluated with color Doppler mode. Subsequently, all patients had MRI and the results were compared with the histopathologic examinations. Results: The sensitivity of MRI for diagnosis of placental adherence defects before the operation was 95%, with a specificity of 95%. In the presence of at least one diagnostic criterion, the sensitivity and specificity of US were 87.5% and 100% respectively, while the sensitivity of color Doppler US was 62.5% with a specificity of 100%. Conclusions: Currently, MRI appears to be the gold standard for the diagnosis of placenta accreta. None of the ultrasonographic criteria is solely sufficient to diagnose placental adherence defects, however, they assist in the diagnostic process.Cel pracy: Celem pracy była ocena przydatności ultrasonografii (US) i rezonansu magnetycznego (MRI) w wykrywaniu nieprawidłowości implantacji łożyska. Materiał i metoda: Do badania włączono pacjentki, które leczone były w Klinice Położnictwa i Ginekologii na Uniwersytecie Ege w Izmirze (Turcja), w okresie od czerwca 2008 do stycznia 2011, z powodu łożyska całkowicie przodującego (n=40). U 20 pacjentek wykonano histerektomię z powodu trudności w oddzieleniu łożyska a u 20 łożysko oddzieliło się samoistnie w trakcie cięcia cesarskiego. Zastosowano skalę Graya do oceny lakun w łożysku, wolnych przestrzeni pod płytą łożyska oraz masy łożyskowej naciekającej płaszczyznę pęcherzowo-maciczną oraz pęcherz moczowy. W badaniu USG z kolorowym Dopplerem oceniano turbulentny przepływ krwi w lakunach wewnątrzłożyskowych oraz wzrost unaczynienia w płaszczyźnie pęcherzowo-macicznej. Następnie wszystkie pacjentki miały wykonane badanie MRI a wyniki porównano z oceną histopatologiczną. Wyniki: Czułość badania MRI dla rozpoznania nieprawidłowości implantacji łożyska przed operacją wyniosła 95% a specyficzność również 95%. Przy obecnym przynajmniej jednym kryterium diagnostycznym, czułość i specyficzność badania USG wyniosły odpowiednio 87,5% i 100%, podczas gdy czułość kolorowego Dopplera wyniosła 62,5% a specyficzność 100%. Wnioski: Obecnie badanie MRI jest złotym standardem wykrywania łożyska wrośniętego. Żadne z ultrasonograficznych kryteriów nie jest wystarczające do rozpoznania nieprawidłowości implantacji łożyska, aczkolwiek pełnią funkcję pomocniczą w procesie diagnostycznym

Kombinacja wewnątrzczaszkowej przezierności i ultrasonografii 3D w diagnostyce wad cewy nerwowej w pierwszym trymestrze ciąży: opis przypadku i przegląd literatury

Neural tube defects are congenital defects of the central nervous system caused by lack of neural tube closure. First trimester screening for aneuploidy has become widespread in the recent years. Fetal intracranial translucency (IT) can be easily observed in normal fetuses in the mid-sagittal plane. The absence of IT should be an important factor taken into consideration in the early diagnosis of open spinal defects. 3D ultrasonography is especially useful in cases of spinal anomalies where the visualization of the fetal structure is insufficient due to fetal position. We present a combination of intracranial translucency and 3D sonography used in the first trimester diagnosis of a neural tube defect case.Wady cewy nerwowej są wrodzonymi defektami centralnego układu nerwowego spowodowanymi brakiem zamknięcia cewy nerwowej. Badania skriningowe w pierwszym trymestrze w kierunku aneuploidii stały się w ostatnich latach bardzo rozpowszechnione. Płodowa przezierność wewnątrzczaszkowa może być oceniona w prawidłowych płodach w płaszczyźnie pośrodkowej. Brak przezierności wewnątrzczaszkowej (IT) powinien być istotnym czynnikiem ryzyka branym pod uwagę we wczesnej diagnostyce otwartych wad cewy nerwowej. Ultrasonografia 3D jest szczególnie przydatna w przypadkach gdy uwidocznienie struktur płodu jest niewystarczające z uwagi na pozycję płodu. Przedstawiamy kombinację przezierności wewnątrzczaszkowej i ultrasonografii 3D w diagnostyce wad cewy nerwowej w pierwszym trymetrze ciąży

Prevalence of Papillary Thyroid Carcinoma is Significantly Higher in Graves Disease with Synchronous Thyroid Nodules

Objective: The association between autoimmunity-related tissue injury and thyroid cancer development remains an area of interest. Evidence suggests that patients with Graves disease (GD) may have an elevated risk for differentiated thyroid cancer. Multicenter studies are needed to gain insight into the correlates of papillary thyroid carcinoma (PTC) identified in this particular group of patients. This study aimed to investigate the prevalence of PTC and synchronous thyroid nodules in thyroidectomy specimens from GD patients in an endemic goiter region. Material and Methods: A retrospective review of institutional pathology records at two tertiary care centers identified 237 surgically treated patients with GD. Patients were categorized as having nodular Graves disease (N-GD) if synchronous nodular thyroid was identified by ultrasonography, while those without synchronous thyroid nodules were categorized as non-nodular or simple Graves disease (S-GD). The prevalence of PTC, histopathological correlates, and demographic characteristics were recorded and compared between groups N-GD and S-GD. Results: One hundred thirty-one and 106 patients were assigned to N-GD and S-GD, respectively. The mean age was significantly higher in N-GD (mean 45.52 years) compared to S-GD (mean 35.18 years) (p0.05). The group of S-GD was enriched in BRAF-like PTCs, whereas N-GD had equal distribution for RAS- and BRAF-like tumors. Conclusion: This study underscores that the majority of PTCs encountered in GD were enriched in low-risk subcentimeter PTCs with a prevalence that varies depending on the presence of underlying nodular thyroid tissue

Nomenclature revision for encapsulated follicular variant of papillary thyroid carcinoma:a paradigm shift to reduce overtreatment of indolent tumors

Although growing evidence points to highly indolent behavior of encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC), most patients with EFVPTC are treated as having conventional thyroid cancer

Severe Primary Hyperparathyroidism Caused by Parathyroid Carcinoma in a 13‐Year‐Old Child; Novel Findings From HRpQCT

Primary hyperparathyroidism is a condition that occurs infrequently in children. Parathyroid carcinoma, as the underlying cause of hyperparathyroidism in this age group, is extraordinarily rare, with only a few cases reported in the literature. We present a 13-year-old boy with musculoskeletal pain who was found to have brown tumors from primary hyperparathyroidism caused by parafibromin-immunodeficient parathyroid carcinoma. Our patient had no clinical, biochemical, or radiographic evidence of pituitary adenomas, pancreatic tumors, thyroid tumors, pheochromocytoma, jaw tumors, renal abnormalities, or testicular lesions. Germline testing for AP2S1, CASR, CDC73/HRPT2, CDKN1B, GNA11, MEN1, PTH1R, RET, and the GCM2 gene showed no pathological variants, and a microarray of CDC73/HRPT2 did not reveal deletion or duplication. He was managed with i.v. fluids, calcitonin, pamidronate, and denosumab prior to surgery to stabilize hypercalcemia. After removal of a single parathyroid tumor, he developed severe hungry bone syndrome and required 3 weeks of continuous i.v. calcium infusion, in addition to oral calcium and activated vitamin D. Histopathological examination identified an angioinvasive parathyroid carcinoma with global loss of parafibromin (protein encoded by CDC73/HRPT2).HRpQCT and DXA studies were obtained prior to surgery and 18-months postsurgery. HRpQCT showed a resolution of osteolytic lesions combined with structural improvement of cortical porosity and an increase in both cortical thickness and density compared with levels prior to treatment. These findings highlight the added value of HRpQCT in primary hyperparathyroidism. In addition to our case, we have provided a review of the published cases of parathyroid cancer in children

Inter-Observer Variation in the Pathologic Identification of Minimal Extrathyroidal Extension in Papillary Thyroid Carcinoma

Background: Extrathyroidal extension (ETE) is a significant prognostic factor in papillary thyroid carcinoma (PTC). Minimal extrathyroidal extension (mETE) is characterized by involvement of the sternothyroid muscle or perithyroid soft tissue, and is generally identified by light microscope examination. Patients with mETE, identified pathologically, are automatically upstaged to pT3. However, the prognostic implications of mETE have been a source of controversy in the literature. Moreover, there is also controversy surrounding the identification of mETE on pathological specimens. The objective of this study was to determine the level of agreement among expert pathologists in the identification of mETE in PTC cases. Methods: Eleven expert pathologists from the United States, Italy, and Canada were asked to perform a review of 69 scanned slides of representative permanent sections of PTC specimens. Each slide was evaluated for the presence of mETE. The pathologists were also asked to list the criteria they use to identify mETE. Results: The overall strength of agreement for identifying mETE was slight (??=?0.14). Inter-pathologist agreement was best for perithyroidal skeletal muscle involvement (??=?0.46, moderate agreement) and worst for invasion around thick-walled vascular structures (??=?0.02, slight agreement). In addition, there was disagreement over the constellation of histologic features that are diagnostic for mETE, which affected overall agreement for diagnosing mETE. Conclusions: Overall agreement for the identification of mETE is poor. Disagreement is a result of both variation in individual pathologists' interpretations of specimens and disagreement on the histologic criteria for mETE. Thus, the utility of mETE in staging and treatment of PTC is brought into question. The lack of concordance may explain the apparent lack of agreement regarding the prognostic significance of this pathologic feature.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140271/1/thy.2015.0508.pd

Inter-Observer Variation in the Pathologic Identification of Extranodal Extension in Nodal Metastasis from Papillary Thyroid Carcinoma

Background: Extranodal extension (ENE) in lymph node metastases has been shown to worsen the prognosis of papillary thyroid cancer (PTC). Despite the clinical significance of ENE, there are no stringent criteria for its microscopic diagnosis, and its identification is subject to inter-observer variability. The objective of this study was to determine the level of agreement among expert pathologists in the identification of ENE in PTC cases. Methods: Eleven expert pathologists from the United States, Italy, and Canada were asked to review 61 scanned slides of representative permanent sections of PTC specimens from Mount Sinai Beth Israel Medical Center in New York. Each slide was evaluated for the presence of ENE. The pathologists were also asked to report the criteria they use to identify ENE. Results: The overall strength of agreement in identifying ENE was only fair (??=?0.35), and the proportion of observed agreement was 0.68. The proportions of observed agreement for the identification of perinodal structures (fat, nerve, skeletal, and thick-walled vessel involvement) ranged from 0.61 to 0.997. Conclusions: Overall agreement for the identification of ENE is poor. The lack of agreement results from both variation in pathologists' identification of features and disagreement on the histologic criteria for ENE. This lack of concordance may help explain some of the discordant information regarding prognosis in clinical studies when this feature is identified.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140272/1/thy.2015.0551.pd