Psammoma Research Articles

Insulinoma

A B S T R A C TInsulinoma is a functional neuroendocrine neoplasm consisting of insulin-producingcells, which produce insulin uncontrollably, causing a hypoglycemic syndrome. TheHypoglycemic syndrome is a result of hyperinsulinemia which causes adrenergicsymptoms and neuroglycopenia. The clinical diagnosis is based on the Whipple triad,insulin, and C peptide levels in a 72-hour fasting state. Generally, insulinoma is abenign neoplasm with a proliferation index of Ki-67 <2%. On histological features, thegrowth pattern of the insulinoma is usually trabecular or solid. Some insulinomas showa tubuloacinar growth pattern with psammoma bodies. We reported one case ofinsulinoma in a 65-year-old woman, who had experienced fainting, cold sweats for 3years, especially when the patient ate late or at midnight while sleeping. A CT scanshowed a tumor mass in the pancreas possibly an insulinoma and a pancreatectomywas performed. The results of the histopathological examination are bu following peerunder Insulinoma.

Clinicopathological Features as Prognostic Predictors of Poor Outcome in Papillary Thyroid Carcinoma.

Simple SummaryThyroid cancer incidence is increasing, with overdiagnosis being the major driver of the thyroid cancer “epidemic”. Papillary thyroid carcinoma, usually with excellent prognosis, sometimes has an aggressive metastatic pattern. This heterogeneity in progression makes it difficult to tailor treatment strategies for an individual patient. We aimed to identify clinicopathological factors associated with papillary thyroid carcinoma recurrence, persistence, and specific mortality. Our study supports that both pre-surgical factors, such as male gender, presence of psammoma bodies, gross extra-thyroidal extension, and lateral compartment lymph node metastases, as well as lymph vessel invasion, venous invasion, presence of necrosis, and incomplete surgical resection, should be taken into consideration regarding treatment and follow-up of PTC patients. The same is true when analysis is restricted to stage I patients. The importance of this report is to emphasize clinical and imaging pre-surgical thyroid cancer patients’ evaluation for an appropriate surgical treatment and patient prognosis.Papillary thyroid cancer (PTC) has an indolent nature and usually excellent prognosis. Some PTC clinicopathological features may contribute to the development of aggressive metastatic disease. In this work, we want to evaluate PTC clinicopathological features that are presurgical prognostic predictors of patients’ outcomes and find which indicators are more adequate for tailoring surgical procedures and follow-up. We studied a series of 241 PTC patients submitted to surgery. All patients’ files and histological tumor samples were reviewed. The 8th edition AJCC/UICC (American Joint Committee on Cancer/Union for International Cancer) Controlstaging system and the 2015 American Thyroid Association risk stratification system were used. Total thyroidectomy was performed in 228 patients, lymphadenectomy in 28 patients. Gross extrathyroidal extension (ETE) was present in 10 patients and 31 tumor resection margins were incomplete. Cervical lymph node metastases (LNMs) were present in 34 patients and distant metastases at diagnosis in four patients. In multivariate analysis, male gender (OR = 15.4, p = 0.015), venous invasion (OR = 16.7, p = 0.022), and lateral compartment LNM (OR = 26.7, p = 0.004) were predictors of mortality; psammoma bodies (PBs) (OR = 4.5, p = 0.008), lymph vessel invasion (OR = 6.9, p < 0.001), and gross ETE (OR = 16.1, p = 0.001) were predictors of structural disease status; male gender (OR = 2.9, p = 0.011), lymph vessel invasion (OR = 2.8, p = 0.006), and incomplete resection margins (OR = 4.6, p < 0.001) were predictors of recurrent/persistent disease. Our study supports that the factors helping to tailor patient’s surgery are male gender, presence of PBs, gross ETE, and lateral compartment LNM. Together with pathological factors, lymph vessel invasion, venous invasion, necrosis, and incomplete surgical resection, should be taken into consideration regarding treatment and follow-up of patients.

Molecular Aspects of Thyroid Calcification.

In thyroid cancer, calcification is mainly present in classical papillary thyroid carcinoma (PTC) and in medullary thyroid carcinoma (MTC), despite being described in benign lesions and in other subtypes of thyroid carcinomas. Thyroid calcifications are classified according to their diameter and location. At ultrasonography, microcalcifications appear as hyperechoic spots ≤ 1 mm in diameter and can be named as stromal calcification, bone formation, or psammoma bodies (PBs), whereas calcifications > 1 mm are macrocalcifications. The mechanism of their formation is still poorly understood. Microcalcifications are generally accepted as a reliable indicator of malignancy as they mostly represent PBs. In order to progress in terms of the understanding of the mechanisms behind calcification occurring in thyroid tumors in general, and in PTC in particular, we decided to use histopathology as the basis of the possible cellular and molecular mechanisms of calcification formation in thyroid cancer. We explored the involvement of molecules such as runt-related transcription factor-2 (Runx-2), osteonectin/secreted protein acidic and rich in cysteine (SPARC), alkaline phosphatase (ALP), bone sialoprotein (BSP), and osteopontin (OPN) in the formation of calcification. The present review offers a novel insight into the mechanisms underlying the development of calcification in thyroid cancer.

A CASE OF NONTUBERCULOUS MYCOBACTERIA ASSOCIATED WITH BRONCHIAL ATRESIA

SESSION TITLE: Fellows Chest Infections Posters SESSION TYPE: Fellow Case Report Posters PRESENTED ON: October 18-21, 2020 INTRODUCTION: This case report describes an extremely rare condition of nontuberculous mycobacteria associated with bronchial atresia. To the best of our knowledge, there has been only one case report which described this condition. CASE PRESENTATION: A 35-year-old woman presented to the previous hospital for right back pain and dry cough that persisted for two days. Chest radiograph showed a mass-like shadow in the right lower lung field. Initially, she was diagnosed with pneumonia and antibiotic treatment (clavulanate/amoxicillin and azithromycin) was started. On the eighth day of antibiotic treatment, the abnormal shadow in the right lower lung field on chest radiograph enlarged and she was referred to our hospital for a detailed examination and treatment. On admission, her body temperature was 37.6℃, blood pressure was 145/87mmHg, and other vital signs were normal. Laboratory test values, including serum interleukin-2 receptor, antinuclear antibody, PR3-ANCA and MPO-ANCA, were within normal limits. Contrast-enhanced chest computed tomography (CT) revealed irregular consolidation in the lower lobe of the right lung with internal calcification, emphysematous changes around the lesion, a Y-Shaped opacity considered to be an obstructed bronchus. Fiberoptic bronchoscopy showed no abnormal findings. From these findings, some infectious disease associated with congenital lung malformation was suspected. Her slight fever persisted and the lesion in the right lower lobe did not improve despite antibiotic treatment. Therefore, she underwent right lower lobectomy for the definitive diagnosis and treatment. Histological examination of the surgical specimen revealed multiple granulomas with multinucleated giant cells, necrosis, and psammoma bodies. BCG stain and Auramine O fluorescence microscopy stain were positive. Finally, PCR of the surgical specimen revealed positive results for Mycobacterium avium. From these findings, the patient was diagnosed with nontuberculous mycobacteria associated with bronchial atresia, and her condition was stable after the surgery without any treatment. DISCUSSION: Nontuberculous mycobacteria complicated with bronchial atresia is an extremely rare condition. To the best our knowledge, there is only one case report describing this condition in the English literature (1). For making a definitive diagnosis, necrotizing sarcoid granulomatosis (NSG) was a very important differential disease. NSG is also an extremely rare disease characterized by pulmonary infiltrations with pathological findings, consisting of granulomas with variable extent of necrosis and vasculitis (2). In our patient, BCG stain and PCR identified Mycobacterium avium, and NSG was excluded. CONCLUSIONS: We herein described a rare case of nontuberculous mycobacteria associated with bronchial atresia. We believe that our case will add to our understanding and recognition of the spectrum of this rare condition. Reference #1: Matsuoka K, Ueda M, Miyamoto Y. Mycobacterium avium infection complicating congenital bronchial atresia. Asian Cardiovasc Thorac Ann 2016 Oct;24(8):808-810. Reference #2: Liebow AA. The J. Burns Amberson lecture--pulmonary angiitis and granulomatosis. Am Rev Respir Dis 1973 Jul;108(1):1-18. DISCLOSURES: No relevant relationships by Yuri Hiramatsu, source=Web Response No relevant relationships by Takafumi Kawabata, source=Web Response No relevant relationships by Yosuke Murakami, source=Web Response No relevant relationships by Saori Nishizawa, source=Web Response No relevant relationships by Mitsukuni Sakabe, source=Web Response No relevant relationships by TAKUTO SUEYASU, source=Web Response No relevant relationships by Kazunori Tobino, source=Web Response

The suitability of NONO-TFE3 dual-fusion FISH assay as a diagnostic tool for NONO-TFE3 renal cell carcinoma

NONO-TFE3 RCC is a subtype of Xp11.2 translocation renal cell carcinoma (RCC). So far, only a small amount of NONO-TFE3 RCC have been reported owing to lack of effective diagnosis methods. Utilizing the novel dual-fusion fluorescence in situ hybridization (FISH) probe reported here, 5 cases of NONO-TFE3 RCC were identified and were ultimately confirmed by RT-PCR. Histopathology, all 5 cases were consisted by sheets of epithelial cells and papillary architecture. The cytoplasm was abundantly clear, and nucleoli was not prominent. Besides, the nuclear palisading, subnuclear vacuoles and psammoma bodies were identified. The most distinctive features were strong positive TFE3 staining but equivocal split signals of the TFE3 probe, which might lead to the misdiagnosis of Xp11.2 translocation RCC. The median age and median tumor size of the five patients were 41.2 years and 3.6 cm, respectively. A median following follow-up of 27 months showed moderate disease progression and prognosis in NONO-TFE3 RCC patients. In conclusion, the present study demonstrates the effectiveness and reliability of the NONO-TFE3 dual-fusion FISH probe for diagnosing NONO-TFE3 RCC. Suspected cases of Xp11.2 translocation RCC showing biphasic pattern, strong positive TFE3 staining, and equivocal split signals in the TFE3 FISH assay indicated a possibility of NONO-TFE3 RCC.

Determining the significance of psammoma bodies in pelvic washings: A 10-year retrospective review.

Pelvic washing specimens are relatively common and are submitted for patients undergoing gynecologic surgery to evaluate them for metastatic or occult disease. Psammoma bodies are a relatively uncommon finding in these specimens. To date, large-scale studies of their cytologic-histologic correlates and thus clinical significance have been limited. A 10-year retrospective search for all pelvic washing specimens was performed, and all cases were reviewed for the presence of psammoma bodies. The findings for the corresponding surgical pathology specimens were then catalogued. Psammoma bodies were present in 138 cases (3.6% of 3840 total pelvic washings). More than half of the cases (n=73 [53%]) were associated with benign processes, including mesothelial hyperplasia (n=44), endosalpingiosis (n=11), endometriosis (n=11), and ovarian cystadenoma/cystadenofibroma (n=7). Nineteen cases (14%) were associated with serous borderline tumors. Malignancies were noted in a third of the cases (n=46 [33%]) and were most frequently low-grade serous adenocarcinomas (n=15), high-grade serous adenocarcinomas (n=11), or endometrioid endometrial carcinomas (n=8). Patients found to have benign processes (median age, 50 years) or borderline disease (median age, 56 years) were significantly younger than patients with malignancies (median age, 65 years; P<.0001). In addition, the correlation of cytologic interpretation categories with concurrent histopathologic findings showed that cytologic analysis was highly sensitive and specific in determining the nature of underlying processes. The majority of psammoma bodies noted in pelvic washings were associated with benign processes or borderline tumors, with approximately a third of the cases associated with malignancies. Psammoma bodies in pelvic washings from younger patients were significantly more likely to be associated with benign processes or borderline tumors.

GORLIN SYNDROME SYNCHRONIC WITH ORAL SQUAMOUS CELL CARCINOMA: A CASE REPORT

The nevoid basal cell carcinoma syndrome (NBCCS) is a genetic disorder that affects the PTCH gene, which is highly associated with tumor suppression. It presents a case of NBCCS diagnosed in a 49-year-old Caucasian male. His medical history has shown a great number of surgical procedures for the removal of lesions that are common to the syndrome. One of the lesions was removed from the mandible and sent for biopsy. The patient was diagnosed by means of a jaw biopsy conducted by a buccomaxillofacial surgeon, and histopathologic sections showed a diagnosis of odontogenic keratocyst (OKC) and squamous cell carcinoma (SCC). Also, in the same section, some calcified materials were found that refer to psammoma bodies. The patient is still under care with an oncologic surgeon for future surgeries given the nature of the disorder. This case illustrates the importance of a multidisciplinary team in the diagnosis and treatment of patients with NBCCS. The nevoid basal cell carcinoma syndrome (NBCCS) is a genetic disorder that affects the PTCH gene, which is highly associated with tumor suppression. It presents a case of NBCCS diagnosed in a 49-year-old Caucasian male. His medical history has shown a great number of surgical procedures for the removal of lesions that are common to the syndrome. One of the lesions was removed from the mandible and sent for biopsy. The patient was diagnosed by means of a jaw biopsy conducted by a buccomaxillofacial surgeon, and histopathologic sections showed a diagnosis of odontogenic keratocyst (OKC) and squamous cell carcinoma (SCC). Also, in the same section, some calcified materials were found that refer to psammoma bodies. The patient is still under care with an oncologic surgeon for future surgeries given the nature of the disorder. This case illustrates the importance of a multidisciplinary team in the diagnosis and treatment of patients with NBCCS.

On the chemical composition of psammoma bodies microcalcifications in thyroid cancer tissues

Recently the knowledge of chemical composition of pathological mineralizations is an important topic extensively studied because it could give more in-depth information to understand pathologies themselves and to improve prevention methods. In this work, psammoma bodies (PBs) microcalcifications in thyroid cancer tissue are investigated by different and complementary analytical methods as: micro-Fourier transformed spectroscopy, X-ray fluorescence spectroscopy, Inductively Coupled plasma Optical Emission Spectroscopy (ICP-OES) and scanning electron microscopy (SEM) with energy dispersive X-ray spectroscopy imaging (EDX). For the first time the micro-FTIR analysis of the only inorganic phase isolated from PBs was reported. Signals of the recorded spectrum showed that the main component of the calcifications is the amorphous carbonated calcium phosphate, and the IR spectrum of thyroid PBs is strongly consistent with that of PBs in human ovarian tumors. The XRF and the ICP analysis detected also the presence of iron ad zinc in thyroid PBs. These results are validated by scanning electron microscopy (SEM) with energy dispersive X-ray spectroscopy imaging (EDX) carried out on tissue samples of the papillary thyroid carcinoma. By these analytical methods magnesium and sodium were detected within PBs while the presence of iron was confirmed by the Perls test. Summarizing the results of applied analytical methods, the main detected elements within the thyroid psammoma bodies are Ca, P, Mg, Na, Fe and Zn. Magnesium and sodium are found in malignant breast cancer microcalcifications, thus they seem correlated to neoplastic transformation. The Fe and Zn elements could give information about the origin of these pathological microcalcifications.

Abstract 3525: Epidemiology and clinicopathology prognostic factors of TFEB translocation renal cell carcinoma (TBRCC): Analysis of updated pooled database

Abstract Renal cell carcinomas harboring the t(6;11) (p21;q12) translocation with a specific Alpha(MALAT1)-TFEB gene fusion is a recognized rare subtype of the Microphthalmia Transcription factor (MiT) family of translocation RCC. TBRCC is an indolent disease that occurs at a younger age. Though it may take on a wide spectrum of morphology, TBRCC has been classically characterized by distinctive biphasic morphology with larger epithelioid cells and smaller cells clustered around eosinophilic spheres formed by basement membrane material. This analysis was conducted to update and expand our existing knowledge of this rare disease. In order to study the demographic characteristics, cytogenetic and molecular signatures, survival, and prognostic factors, we compiled a pooled database of 140 cases. Kaplan-Meier survival curves were constructed. Cox proportional-hazards model and Log-rank tests were used to assess the influence of demographic and clinicopathologic factors on survival. The median age was 32 (3-78) years with a peak incidence between ages 17 and 30 years. Males and females were afflicted equally. The median overall survival (OS) of the whole group was not reached with more than 78% alive at 10 years. The group's median disease-free survival (DFS) was 96 months. Six percent of this cohort recurred. Among patients who recurred, the median time to recurrence was 24(6-75) months. Sex did not impact OS or DFS. Similarly, the molecular partner of the TFEB gene fusion, Alpha (MALAT1) versus others, did not seem to impact OS or DFS. The presence of necrosis seemed to adversely impact OS (HR:14.3, p&amp;lt;0.0001) and DFS (HR:14.4, p&amp;lt;0.0001). Nuclear grade negatively impacted DFS, the higher the grade the worse the DFS. The presence of eosinophilia, psammoma bodies, and pigmentation did not affect OS or DFS. Similarly, the histologic morphology, biphasic vs others, did not affect OS or DFS. Multivariate analysis revealed older age (HR:1.08, p=0.01) and larger tumor size (HR:10.12, p=0.002) adversely impacted OS. This study presents an updated epidemiologic and clinicopathologic data from a pooled cohort of patients with TBRCC. Age, size, and necrosis were found to adversely impact the OS. However, higher nuclear grade only adversely impacted the cohort's DFS. Citation Format: Philip A. Haddad, Dalia Hammoud, Kevin Gallagher. Epidemiology and clinicopathology prognostic factors of TFEB translocation renal cell carcinoma (TBRCC): Analysis of updated pooled database [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3525.

RET, NTRK, ALK, BRAF, and MET Fusions in a Large Cohort of Pediatric Papillary Thyroid Carcinomas.

Background: Pediatric papillary thyroid carcinoma (PTC) is a rare malignancy, but with increasing incidence. Pediatric PTCs have distinct clinical and pathological features and even the molecular profile differs from adult PTCs. Somatic point mutations in pediatric PTCs have been previously described and studied, but complex information about fusion genes is lacking. The aim of this study was to identify different fusion genes in a large cohort of pediatric PTCs and to correlate them with clinical and pathological data of patients. Methods: The cohort consisted of 93 pediatric PTC patients (6-20 years old). DNA and RNA were extracted from fresh frozen tissue samples, followed by DNA and RNA-targeted next-generation sequencing analyses. Fusion gene-positive samples were verified by real-time polymerase chain reaction. Results: A genetic alteration was found in 72/93 (77.4%) pediatric PTC cases. In 52/93 (55.9%) pediatric PTC patients, a fusion gene was detected. Twenty different types of RET, NTRK3, ALK, NTRK1, BRAF, and MET fusions were found, of which five novel, TPR/RET, IKBKG/RET, BBIP1/RET, OPTN/BRAF, and EML4/MET, rearrangements were identified and a CUL1/BRAF rearrangement that has not been previously described in thyroid cancer. Fusion gene-positive PTCs were significantly associated with the mixture of classical and follicular variants of PTC, extrathyroidal extension, higher T classification, lymph node and distant metastases, chronic lymphocytic thyroiditis, and frequent occurrence of psammoma bodies compared with fusion gene-negative PTCs. Fusion-positive patients also received more doses of radioiodine therapy. The most common fusion genes were the RET fusions, followed by NTRK3 fusions. RET fusions were associated with more frequent lymph node and distant metastases and psammoma bodies, and NTRK3 fusions were associated with the follicular variant of PTC. Conclusions: Fusion genes were the most common genetic alterations in pediatric PTCs. Fusion gene-positive PTCs were associated with more aggressive disease than fusion gene-negative PTCs.

Detailed characterization of metastatic lymph nodes improves the prediction accuracy of currently used risk stratification systems in N1 stage papillary thyroid cancer.

The characteristics of metastatic lymph nodes (MLNs) have been investigated as important predictors of recurrence and progression in papillary thyroid cancer (PTC). However, clinically applicable risk stratification systems are limited to the assessment of size and number of MLNs. This study investigated the predictive value of detailed characteristics of MLNs in combination with currently used risk stratification systems. We retrospectively characterized 2811 MLNs from 9014 harvested LNs of 286 patients with N1 PTC according to the maximum diameter of MLN (MDLN), maximum diameter of metastatic focus (MDMF), ratio of both diameters (MDMFR), lymph node ratio (LNR, number of MLNs/number of total harvested LNs), presence of extranodal extension (ENE), desmoplastic reaction (DR), cystic component, and psammoma body. Factors related to the size and number of MLNs were associated with increased risk of recurrence and progression. Extensive presence of ENE (>40%) and DR (≥50%) increased the risk of recurrence/progression. The combination of MDLN, LNR, ENE, and DR had the highest predictive value among MLN characteristics. Combination of these parameters with ATA risk stratification or 1-year response to therapy improved the predictive power for recurrence/progression from a Harrell's C-index of 0.781 to 0.936 and 0.867 to 0.960, respectively. The combination of currently used risk stratification systems with detailed characterization of MLNs may improve the predictive accuracy for recurrence/progression in N1 PTC patients.

Primary ovarian serous psammocarcinoma-a case report with mini literature review

Serous psammocarcinoma is a rare subtype of serous carcinoma in which a significant number of psammoma bodies are present histologically. Because it is an extremely rare disease, the pathogenesis of the disease remains unclear. Here we present a case of primary ovarian serous psammocarcinoma in which computed tomography (CT) imaging of the abdomen was useful for the diagnosis. A female patient was referred to our department with a complaint of abdominal distention. Pelvic magnetic resonance imaging revealed a multifocal tumor with a papillary enhancement in the right appendicular region, and abdominal CT imaging exhibited marked calcification of the enhancement. She underwent a laparotomy for suspected right ovarian cancer. As postoperative pathological examination revealed dominant stromal infiltration of psammoma bodies beneath peritoneum, this case was diagnosed as primary ovarian serous psammocarcinoma at FIGO Stage IIB. The patient was treated with six courses of paclitaxel plus carboplat in after the surgery. She is currently under outpatient observation without any signs of recurrence after 8 years of treatment. The case of significant calcification of the intra cystic enrichment on CT imaging is considered to be a case of this disease.

Histopathological Spectrum of Meningiomas with Emphasis on Prognostic Role of Ki67 Labelling Index.

Background & Objective:Meningiomas are the most frequently encountered primary non-glial tumors of the central nervous system (CNS). The Ki67 labelling index (Ki67LI) is a proliferation marker that may prove useful in determining the histological grade. This study aims at: 1) Studying the frequency, grade and histomorphological spectrum of meningiomas, 2) Evaluating 20 histological parameters and determining its utility in grading meningiomas and 3) Comparing the Ki67LI in the various subtypes and WHO grades.Methods:The cases of meningiomas diagnosed in our Department from June 2009 to May 2014 were included. The clinical details, grade and 20 histological parameters: mitosis, vesicular nuclei, macronucleoli, nuclear pleomorphism, scattered bizarre nuclei, hypercellularity, sheeting, lymphocytes, small cell change, foam cells, ossification, necrosis, papillary change, lipidization, psammoma bodies, vascularization, brain invasion, dural invasion, bone invasion and other soft tissue invasion were recorded for each case. The average and highest Ki67LI was recorded as percentage and number per high power field. Results:A total of 175 cases of meningioma were included: grade I (145), grade II (30). Atypical histological features like hypercellularity, sheeting, etc. were common in grade II tumors. Increased vascularity, lymphocytes and psammoma bodies were common in grade I tumors. Ki67LI (highest) ranged from 1-6% in grade I and 5-12% in grade II tumors.Conclusion:Among different methods showing mitotic activity, Ki67% (highest) was the most statistically significant LI in differentiating grade I and grade II tumors. The median Ki67% (highest) was 4% for grade I and 7% for grade II tumors.

A Clinicopathologic Study and Descriptive Analysis of "Atypical Endosalpingiosis".

"Atypical endosalpingiosis" (AE) is a diagnostic term used variably among pathologists to denote peritoneal lesions exhibiting architectural changes and/or cytologic atypia intermediate between endosalpingiosis and primary peritoneal serous borderline tumor (SBT). AE is a contentious entity and is not recognized in the current World Health Organisation Classification. We report a series of 10 cases classified as AE, in attempt to further characterize this lesion. The patients ranged in age from 24 to 72 yr (mean, 39.7 yr) and the commonest presenting complaint was abdominal pain. Operative findings usually comprised small peritoneal nodules and/or fibrous adhesions, predominantly involving the pelvis. The lesions were either mesothelial or submesothelial in location and typically exhibited mixed tubular and papillary architecture, sometimes with minor components of solid, cribriform or single cell growth. Epithelial multilayering was present in all cases but usually involved <25% of the lesion. There was mild nuclear atypia and mitoses were infrequent or absent. No infiltrative growth was seen. The stroma was usually inflamed and psammoma bodies were consistently present. Features which prompt a diagnosis of AE rather than endosalpingiosis include architectural alterations, usually in the form of papillae, epithelial multilayering, and mild nuclear atypia. While the extent of these findings is often less than occurs in primary peritoneal SBT or in extraovarian implants in association with an ovarian SBT, robust histologic criteria for distinction of AE from SBT do not exist. Despite this, the term AE may be of use when dealing with atypical peritoneal proliferations resembling SBT but which are limited in extent or fall just short of criteria for an unequivocal diagnosis of primary peritoneal SBT. In our series, lesions diagnosed as AE did not result in adverse clinical outcome (follow-up in 8 patients from 4 to 84 mo). Further study is required to determine whether a diagnostically reproducible and clinically relevant intermediate lesion exists between endosalpingiosis and SBT.

Psammoma bodies in Papanicolaou tests and associated factors to predict an underlying malignancy: a clinicopathological analysis of 10 cases

Psammoma bodies (PBs) are rarely encountered in Papanicolaou tests. They have been described in benign and malignant conditions of the gynecologic tract and peritoneum. The aim of our study was to reveal the associated factors with PBs in Papanicolaou tests to predict an underlying malignancy, particularly in the absence of atypical glandular cells (AGCs). From 1987 to 2018, all gynecologic cytology reports with PBs were identified from the computerized pathology database of Baystate Medical Center, Springfield, Massachusetts. Patients with previous history of gynecologic and/or peritoneal malignancy were excluded. Clinical information and follow-up data were obtained from chart review. PBs were found in 10 of the 1,497,540 Papanicolaou tests (0.0006%). Six patients with age ranging from 19 to 58 years (mean age, 37.6 years) had benign outcome (eg, endometritis, ovarian serous cystadenofibroma). Four patients with age ranging from 31 to 54 years (mean age, 41.7 years) had borderline/malignant outcome (eg, ovarian borderline serous tumor, peritoneal serous psammocarcinoma). All patients with borderline/malignant outcome had family history of cancer and/or gene mutation (eg, sister with breast cancer, father with BRCA-1 mutation). PBs were accompanied by AGCs in 2 of 4 borderline/malignant cases. PBs should not be ignored in Papanicolaou tests because of their possible association with an underlying malignancy. To our knowledge, this is the first study demonstrating that relevant family history of cancer and/or gene mutation may be a helpful clue regarding an underlying malignancy, especially in the absence of accompanied AGCs with PBs.

BRAF Exon 15 Mutations in Papillary Carcinoma and Adjacent Thyroid Parenchyma: A Search for the Early Molecular Events Associated with Tumor Development.

BRAF exon 15 mutations are the most common molecular alterations found in papillary thyroid carcinoma (PTC). To date, there is no information regarding BRAF alterations in the thyroid parenchyma surrounding the tumor. To explore the early events associated with the development of PTC, we used massively parallel sequencing to investigate BRAF exon 15 in 30 PTCs and in 100 samples from the thyroid parenchyma surrounding the tumor. BRAF p.V600E was identified in 19/30 PTCs (63.3%). BRAF p.V600E mutations were identified in the tissue adjacent the PTC only in samples containing psammoma bodies. The other samples were either BRAF wild type (WT) or carried BRAF non p.V600E mutations. Specifically, BRAF p.G593D, -p.A598T, -p.V600M, -p.R603Q, -p.S607F, and -p.S607P were identified in 4 of 36 (11.1%) samples with follicular cell atypia, in 2 of 16 (12.5%) with follicular cell hyperplasia, and in 1 of 33 (3.0%) histologically normal samples—Only in tissue surrounding BRAF p.V600E mutated PTCs. These mutations are predicted to affect protein function in silico but, in vitro, have kinase activity and BRAF phosphorylation levels similar to BRAF WT. No BRAF exon 15 mutations were identified in samples adjacent to PTCs that were BRAF WT. A mutagenic process affecting BRAF exon 15 occurs in a subset of thyroid glands that develop BRAF p.V600E mutated PTCs.

Predictive Risk-scoring Model For Central Lymph Node Metastasis and Predictors of Recurrence in Papillary Thyroid Carcinoma

There are about half of papillary thyroid carcinoma (PTC) patients with the experience of central lymph node metastasis (CLNM), while the model to predict high-risk groups of CLNM from PTC patients is uncertain. The aim of this study was to evaluate candidate risk factors of CLNM and identify risk factors of recurrence to guide the postoperative therapeutic decision and follow-up for physicians and patients.A total of 4107 patients(4884 lesions) who underwent lymph node dissection in two hospitals from 2005 to 2014 were evaluated. CLNM risk was stratified and a risk-scoring model was developed on the basis of the identified independent risk factors for CLNM. Cox’s proportional hazards regression model was used to investigate the risk factors for recurrence.CLNM was proved in 37.96% (1559/4107) of patients and 33.96% (1659/4884) of lesions. In the multivariate analysis, Male, Age ≤35 years, Tumor size >0.5 cm,Lobe dissemination (+), Psammoma body (+), Multifocality and Capsule invasion (+) were independent risk predictors of CLNM (P < 0.01). A 14-point risk-scoring model was built to predict the stratified CLNM in PTC patients and the area under receiver operating characteristic curve of the model for the prediction of CLNM was 0.672 (95% CI: 0.656–0.688) (P < 0.01). COX regression model showed that Tumor size >0.5 cm, Lobe dissemination (+), Multifocality and CLNM were significant risk factors associated with poor outcomes. The research suggested that prophylactic CLN dissection could be performed in patients with total score ≥4 according to the risk-scoring model, and more aggressive treatment and more frequent follow-up should be considered for patients with Tumor size >0.5 cm, Lobe dissemination (+), Multifocality and CLNM.

Carcinoma papilar difuso de tiroides: Microcalcificaciones fuera del nodulo tiroideo

Abstract INTRODUCTION: The incidence of thyroid papillary cancer (PTC) has increased from 1975 to 2015. Ultrasound is effective for predicting thyroid malignancy based on published criteria. All of these criteria focus on thyroid nodules but also 2% of the cases may appear as diffuse punctuate echogenic foci without an identifiable nodule. CASE: A 17-year-old female with a 3-month history of a palpable mass on the right anterior side of the neck without any further symptoms. Neck ultrasound revealed multiple punctuate echogenic foci scattered along the thyroid parenchyma with a 6 mm nodule TI-RADS 5 on the left lobe, lymph nodes with cystic and solid components, loss of echogenic hilum and punctuate echogenic foci. The patient underwent a total thyroidectomy with bilateral lymphadenectomy. The pathology report revealed diffuse distribution of papillary cancer with a nodule on the left lobe and metastatic disease on the lymph nodes. DISCUSSION: Microcalcifications are highly suggestive of PTC. Punctuate echogenic foci correlate in pathology with a form of dystrophic calcifications, called Psammoma bodies, which are deposited in nonviable tissue. Chronic thyroiditis may also present dystrophic calcifications. Thus, a normal thyroid parenchyma with microcalcifications should encourage the radiologist perform a fine-needle aspiration biopsy (FNAB). Recent studies suggest that lobectomy is a viable option and should be pursued in the setting of localized PTC (&lt;2cm). A lobectomy should not be performed in patients with diffuse microcalcifications since it would result in an unfavorable outcome. CONCLUSIONS: Diffuse microcalcifications should immediately make the radiologist to suspect diffuse PTC as a first diagnostic option. Key words: Thyroid papillary cancer (PTC), Ultrasound (US), Psammoma, Chronic thyroiditis

Histopathological and Clinical Features as Prognostic Factors of Atypical Meningiomas.

To analyze the correlation of clinicopathologic prognostic parameters with atypical meningiomas (AMs) and recurrence development as well as progression-free survival (PFS). The neuropathology archive and hospital records of 75 patients with AM who underwent surgery in our institution between 2010 and 2019 were retrospectively reviewed. The pathological revision was performed according to the 2016 World Health Organization (WHO) criteria. Other clinicopathological parameters, such as age, gender, tumor location, preoperative tumor size, degree of resection, Psammoma body, nuclear atypia, main histological pattern, Ki67 labeling index (LI), radiotherapy, and dura and bone invasion, were also analyzed. Statistically, univariate and multivariate analyses were assessed to determine their potential impact on recurrence-related prognostic factors. Recurrence occurred in 20 patients. The mean PFS and follow-up time were 38.9 and 44.8 months, respectively. In univariate analysis, clinical and pathological features such as age of ?55 years, female sex, skull base tumor location, larger preoperative tumor size, increased mitotic count, small cells, hypercellularity, sheeting, necrosis, and dura and bone invasion were remarkable in patients with recurrence, but were not statistically significant. In multivariate analysis, increased mitotic activity and brain invasion either considered alone or combined were significantly associated with PFS. Nuclear atypia was also not associated with both tumor recurrence and PFS. However, clinical features did not significantly influence the PFS. This study found that recurrence could not be predicted by the presence of any of the clinicopathological features of AMs. We believe that molecular variables determined through routine neuropathological analysis will be needed in the future.

Pulmonary-derived papillary adenomatoid proliferation arising in ovarian mature cystic teratoma

Introduction: Primary lung papillary neoplasms are very rare and less than 30 cases of papillary adenomas have been described. Lung-derived papillary lesions arising in ovarian mature cystic teratoma are extremely rare and, to the best of the authors’ knowledge, only one case has been reported. Herein they report the second case and discuss the differential diagnoses. Case Report: A 32-year-old woman presented with bilateral ovarian mature cystic teratoma (MCT) (“dermoid”). The right side teratoma, very close to the thyroid tissue (struma ovarii), presented a morphologically benign mass, with complex papillary structures and psammoma bodies, which mimicked a thyroid papillary carcinoma (TPC). Immunohistochemistry showed diffuse positive staining with EMA, cytokeratins, and patchy positive staining with TTF1 and surfactant apoprotein A. Thyroglobulin, PAX-8, HMBE1, chromogranin, synaptophysin, CD56, CEA, p63, and BRAF were negative. The work-up for metastasis was negative. Close clinical and instrumental follow-up was decided following consultation with the lung and gynaecological multidisciplinary team. Conclusion: This is the second case of benign appearing, lung-derived papillary neoplasm arising in an ovarian MCT. In view of the clinical context, histological criteria used in lung pathology cannot be applied with confidence in this case. The most appropriate term would be pulmonary-derived papillary adenomatoid proliferation. This novel entity will be useful for pathologists and clinicians in diagnosing and differentiating this very rare disease from other lesions arising in ovarian teratomas.