Papillary Architecture Research Articles

HPB P54 First Reported Case of Primary Serous Cystadenocarcinoma of the Spleen

Abstract Background Tumours of the spleen are uncommon, and the majority are metastases from primary malignancies in other organs. The two main subdivisions of primary malignancies of the spleen are lymphoid and non-lymphoid. Primary splenic cystadenocarcinomas are extremely rare, and only tumours of the mucinous subtype have been recorded. The spleen usually exhibits secondary infiltration from primary cystadenocarcinomas in other organs such as the ovaries and pancreas. Methods We present the case of an elderly white female who was found to have an incidental splenic tumour. This showed interval increase in size on serial imaging and was confirmed to be a complex mass with a cystic component on MRI. After MDT discussion and further investigations, including FDG-PET, EUS and diagnostic laparoscopy, she underwent a distal pancreatectomy, partial gastrectomy and splenectomy for a presumed tail of pancreas adenocarcinoma. Results The splenic hilum contained a large partly cystic tumour conglomerate measuring up to 5.8cm in maximum dimension, which contained thick, dark red, gelatinous material. It was well-circumscribed and demarcated from the rest of the splenic parenchyma, and the distal pancreas appeared to be uninvolved. Histology showed low columnar to cuboidal cells with moderate to patchy marked nuclear pleomorphism, and no cytoplasmic mucin was identified. The tumour had a predominantly papillary and focal tubular architecture, with hierarchical branching of papillae. The neoplastic cells stained positive for CK7, ER and WT1 expression and negative for CK20 and CA. Conclusions Histological and immunohistochemical analyses were consistent with the first recorded case in the literature of primary serous cystadenocarcinoma of the spleen, which we believe developed through malignant transformation of a benign epidermoid cyst. This is the commonest type of true cysts of the spleen and one which has tumorigenic potential, being able to undergo metaplasia and dysplasia. The patient remains well as per her latest follow-up with no evidence of recurrence or metastases. However, given the rarity of splenic cystadenocarcinomas, uncertainty remains on the long-term prognosis and optimal management of such cancers, including adjuvant treatment options.

Role of magnetic resonance imaging to differentiate between borderline and malignant serous epithelial ovarian tumors.

We aimed to differentiate serous borderline ovarian tumors (SBOT) from serous epithelial ovarian carcinomas (SEOC) using morphological and functional MRI findings, to improve the patient management. We retrospectively investigated 24 ovarian lesions diagnosed with SBOT and 64 ovarian lesions diagnosed with SEOC. Additional to the demographic and morphological findings T2W signal intensity ratio, mean apparent diffusion coefficient (ADCmean) and total apparent diffusion coefficient (ADCtotal) values were analyzed and compared between two groups. Bilaterality, pelvic free fluid presence, serum CA-125 level (U/mL), presence of pelvic peritoneal implant were in favor of SEOC. Lower maximum size of solid component and solid size to maximum size ratio, dominantly cystic and solid-cystic appearance, exophytic growth pattern, presence of papiller projection and papillary architecture and internal branching pattern, higher T2W signal intensity ratio, ADCmean and ADCtotal values were in favor of SBOT. Our study revealed that morphological and functional imaging findings were valuable in differentiating BSOT from SEOC.

SAT550 Warthin-like Variant of Papillary Thyroid Carcinoma: An Even Rarer Presentation

Abstract Disclosure: J. Kunadia: None. S. Chablani: None. Introduction: We present a rare case of Warthin-like variant of papillary thyroid carcinoma (WLPTC) with later development of a second primary malignancy. Clinical Case: A 56 year old female with hypertension, hyperlipidemia, ulcerative colitis, asthma, and a strong family history of cancer presented in 2017 for evaluation of an enlarged thyroid gland noted by her primary care provider. Patient was asymptomatic and denied prior thyroid disease and head or neck radiation. Labs demonstrated normal TSH and free T4 levels. TPO antibodies were elevated to 1,155 IU/mL (reference range 0.0 – 5.5 IU/mL). Thyroid US was notable for a diffusely enlarged thyroid gland containing a 1.4 x 0.6 x 1.0 cm solid, hypoechoic nodule without calcifications in the upper pole of the right lobe. Shared decision-making resulted in a plan for continued surveillance. Repeat thyroid US in 2018 demonstrated that this nodule had increased in volume by 56.25%, now measuring 1.4 x 0.75 x 1.25 cm. Fine needle aspiration (FNA) biopsy was performed and positive for papillary thyroid carcinoma (PTC). Patient underwent total thyroidectomy; pathology revealed a 1.2 x 1 x 0.9 cm WLPTC and 0.2 cm papillary thyroid microcarcinoma. There was no evidence of extrathyroidal extension, angioinvasion, or lymph node involvement. Follow-up neck US in 2020 demonstrated a 0.4 cm hypoechoic ovoid structure in the left thyroid bed and an enlarged but morphologically normal-appearing right level II lymph node. Repeat neck US in 2021 showed the appearance of a new 2.8 cm right level II lymph node; FNA was positive for malignancy with negative thyroid transcription factor-1 staining and undetectable thyroglobulin. Patient underwent an excision biopsy of the lymph node, and pathology was consistent with metastatic adenoid cystic carcinoma (ACC). A right submandibular gland lesion detected on subsequent MRI head and neck was resected and confirmed to be the primary source of ACC. Patient was treated with adjuvant radiation therapy with adequate response to therapy. Conclusion: WLPTC is a rare subtype of PTC that accounts for 0.2-1.9% of cases and carries a strong association with Hashimoto’s thyroiditis. It is histologically characterized by papillary architecture, oncocytic changes, nuclear features of PTC, and dense lymphoplasmacytic infiltration of the papillary cores. WLPTC is considered to have a favorable prognosis given its low frequency of lymphovascular invasion and low recurrence risk. This case also highlights the importance of keeping a broad differential when evaluating new findings on neck US in patients with a history of thyroid cancer. Metastases to cervical lymph nodes most commonly occur from head and neck tumors. However, to date, only one other case of PTC with second primary malignancy of salivary ACC has been reported. Presentation Date: Saturday, June 17, 2023

Papillary renal neoplasm with reverse polarity: a clinicopathologic study of 43 cases with a focus on the expression of KRAS signaling pathway downstream effectors

Papillary renal neoplasm with reverse polarity (PRNRP) is a renal tumor with frequent KRAS mutations. In this study, we aimed to report the clinical, histological, and immunohistochemical characteristics of PRNRP and the protein expression of various KRAS signaling pathway downstream effectors in PRNRP. PRNRP samples from patients who underwent surgical resection at Seoul National University Hospital over an 11-year period (January 2011 to December 2021) were analyzed. We identified 43 PRNRPs, defined as papillary renal tumors with a thin papillary architecture, eosinophilic finely granular cytoplasm, and apical nuclear position. Immunohistochemistry revealed typical characteristics of PRNRP, including exclusively positive GATA3 (43/43); highly positive L1CAM (43/43), PAX8 (43/43), and EMA (43/43); and low positive AMACR (4/43), RCC (1/43), and vimentin (1/43). KRAS signaling pathway effectors, such as p-ERK, RalA, and RalB, were highly expressed in PRNRP compared to papillary renal cell carcinoma (pRCC) with low or high nuclear grade (P<.001, all). Compared to pRCC with high nuclear grade, patients with PRNRP exhibited significantly longer progression-free survival (P<.001). PRNRP showed the best clinical outcome, with no disease progression in any of the cases. Our study analyzed the largest number of PRNRP cases and is the first to analyze the association between PRNRP and the KRAS downstream signaling pathway. PRNRP was found at a high frequency among all papillary renal tumors (43/207) and demonstrated a very good prognosis. PRNRP showed high GATA3, L1CAM, PAX8, and EMA protein expression as well as high p-ERK, RalA, and RalB protein expression.

Positive GPNMB Immunostaining Differentiates Renal Cell Carcinoma With Fibromyomatous Stroma Associated With TSC1/2/MTOR Alterations From Others.

Renal cell carcinoma with fibromyomatous stroma (RCCFMS) include ELOC/TCEB1 -mutated renal cell carcinoma (RCC) and those with TSC1/2 / MTOR alterations. Besides morphologic similarity, most of these tumors is known to be diffusely positive for carbonic anhydrase IX and cytokeratin 7 by immunohistochemistry. We previously showed strong and diffuse expression of GPNMB (glycoprotein nonmetastatic B) in translocation RCC and eosinophilic renal neoplasms with known TSC1/2/MTOR alterations. We retrospectively identified molecularly confirmed cases of TCEB1/ELOC -mutated RCC (7 tumors from 7 patients), and RCCFMS with alterations in TSC1/2/MTOR (6 tumors from 5 patients, 1 patient with tuberous sclerosis syndrome). In addition, we included 7 clear cell papillary renal cell tumors (CCPRCTs) and 8 clear cell RCC, as they can also present morphologic overlap with RCCFMS. Morphologically, RCCs with TSC1/2/MTOR alterations and those with TCEB1/ELOC mutations were indistinguishable and characterized by papillary, nested, or tubular architecture, with tumor cells with clear cytoplasm and low nuclear grade. By immunohistochemistry, cytokeratin 7 was positive in 5/7 (71%) of TCEB1/ELOC -mutated RCCs, 6/6 (100%) of RCCs with TSC1/2/mTOR alterations, and 7/7 (100%) of CCPRCTs ( P =not significant). Carbonic anhydrase IX was positive in 7/7 TCEB1/ELOC -mutated RCCs, 6/6 (100%) of RCCs with TSC1/2/MTOR alterations, and 7/7 (100%) of CCPRCTs ( P =NS). GPNMB was strongly and diffusely positive in all tumors with TSC1/2/MTOR alterations (6/6), while negative in all TCEB1/ELOC -mutated RCCs (0/6), or CCPRCTs (0/7) ( P =0.002). Two of 8 clear cell RCC showed focal weak staining, while 6/8 were negative. In conclusion, the results support the use of GPNMB to distinguish RCCFMS with TSC1/2/MTOR alterations from others with similar morphology.

Diagnostic clues for hyalinizing trabecular tumor on fine needle aspiration cytology.

The hyalinizing trabecular tumor (HTT) is a rare benign neoplasm of the thyroid gland. This neoplasm has overlapping cytological features with Papillary Thyroid Carcinoma, Medullary Carcinoma and Follicular Neoplasm with Nuclear Features of Papillary Carcinoma. This can lead to misdiagnosis of malignancy in fine needle aspiration (FNA) cytology specimens with unnecessary total thyroidectomy. The aim of this study is to determine if there are some cytological features that could help us to suspect HTT on FNA specimens and avoid radical surgery. With this purpose we have collected 6 cases diagnosed of HTT in Hospital Clínico San Carlos of Madrid (Spain) in the last 10 years and reviewed the cytological specimens. We conclude that the presence of hyaline material in FNA specimens of HTT is a constant feature being a diagnostic clue. We must be cautious not to confuse it with dense colloid or amyloid material, the latter seen in Medullary Carcinoma. Papillary architecture and fibrovascular cores are not present in a HTT. Special stains as ki-67, calcitonin and Congo Red staining could help us in achieving the correct diagnosis. We feel the cytopathologists must be aware of the distinguishing features of this lesion, mainly the typical hyaline material to achieve a proper diagnosis and be able to reduce unnecessary aggressive management of these patients.

DICER1 Mutations Do Not Always Indicate Dismal Prognosis in Pediatric Poorly Differentiated Thyroid Carcinomas.

Progress in the field of pediatric thyroid pathology has linked DICER1 mutations to benign follicular cell-derived thyroid tumors (e.g., follicular adenoma with papillary architecture, follicular nodular disease), low-risk follicular cell-derived differentiated thyroid carcinomas and PDTCs enriched in fatal or recurrent/progressive disease. The dismal outcome of DICER1-harboring pediatric PDTCs stems from a limited number of reported patients' data given the rarity of pediatric PDTCs. In light of the former observations, the current study assessed clinicopathological variables of a series of 5 pediatric (≤ 18 years old) PDTCs using the Turin criteria (WHO 2022) and also examined the status of DICER1 and TERT promoter mutations. Five PDTCs (3 males, 2 females) were included in the study. The mean age at the time of diagnosis was 15.4 years. No patients had a history of DICER1 syndrome-related tumors or other clinicopathological diagnostic features of DICER1 syndrome. The mean tumor size was 3.9 cm. All tumors were completely submitted for microscopic examination. There was increased mitotic activity ranging from 3 to 10 mitoses per 2 mm2. Tumor necrosis was present in two cases. No PDTC harbored TERT promoter mutation. DICER1 hot spot mutation was identified in one (20%) tumor. The DICER1-mutant tumor had neither associated differentiated thyroid carcinoma component nor other pathological findings in the adjacent thyroid parenchyma. The DICER1-mutant PDTC showed widely invasive growth confined to the thyroid parenchyma. Despite the widely invasive growth, the tumor lacked vascular invasion. Two DICER1 wild-type PDTCs had lymphocytic thyroiditis and another one had underlying follicular nodular disease and/or follicular adenomas. Three DICER1 wild-type PDTCs also had an associated differentiated thyroid carcinoma component with no high-grade features. No abnormal p53 expression (overexpression or global loss) was recorded in all tested tumors. Four patients had follow-up data with a mean follow-up time of 60.25 months (range: 18-86 months). One patient with no evidence of disease recurrence died of anunrelated cause after 18 months of the initial surgery, all remaining patients were alive with no distant metastasis at their last visit. Of the 4 patients with lymph node (LN) dissection, one DICER1 wild-type PDTC had recurrent nodal disease. During the follow-up period (72 months), no local recurrence or distant metastases was detected in the DICER1-mutant PDTC. Taken together all reported findings from earlier series, DICER1 mutations alone may not necessarily indicate dismal outcome in a subset of pediatric PDTCs. The occurrence of additional genomic alterations as discussed in some earlier reports may be contributing to tumor progression or aggressivity of pediatric PDTCs. The lack of vascular invasion in the current DICER1-mutant pediatric PDTC may also explain an indolent biologic outcome. The risk escalation of DICER1 mutations should integrate the status of additional genetic events and well-established pathologic variables in order to ensure predictive dynamic risk stratification in DICER1-mutant pediatric PDTCs. Additional studiesare needed to corroborate the findings of this study and advance our knowledge in pediatric thyroid neoplasia.

The Impact of En-bloc Transurethral Resection of Bladder Tumour on Clinical, Pathological and Oncological Outcomes: A Cohort Study.

Background En-bloc transurethral resection of bladder tissue (ETURBT) has recently been proposed as a good alternative technique to trans-urethral resection of bladder tissue (TURBT) in terms of outcomes for bladder carcinoma. This study aims to assess the effectiveness of the technique in terms of clinical, pathological and oncological outcomes. Methodology In this prospective study, data was collected from patients who underwent ETURBT for bladder space-occupying lesions between June 2021 and June 2022. Demographic characteristics, tumour characteristics, and postoperative outcomes were recorded. Results A total of 52 patients were studied with the majority being male and a mean age of 50.87 years. Smoking was recorded in 22 (38.5%) patients and 8 (15.4%) were on antiplatelet therapy. The majority fell in the American Society of Anesthesiology (ASA) class I (59.6%). Most of the tumours were solitary (90.4%), primary (82.8%), papillary architecture (73.1%), and between 1-3 cm in size. The lateral wall was the most common position, and detrusor muscle was seen in 98.1% of the specimens. T1 stage (57.7%) and low grade (67.3%) were the common characteristics noted. 76.9% of the ETURBT was conducted using monopolar cautery. Recurrence was noted in 3 (5.8%) and bladder perforation in 1 patient (1.9%). Cautery artifact was seen in six patients (11.5%) and obturator jerk in nine patients (17.3%). Conclusion Our study suggests thatETURBT is atechnique with a good success rate for bladder tumours less than 3 cm in size. The benefitsincludehigh chances of detrusor sampling while minimising crush artefacts and cautery damage. Specimen retrieval was challenging when the bladder tumour was solid and over 2 cm.

Computed tomography (CT) characteristics and pathologic basis of ciliated muconodular papillary tumors of the lung.

Ciliated muconodular papillary tumor (CMPT) is a rare pulmonary tumor with papillary architecture. Most studies have focused on the clinicopathological features of CMPT, while computed tomography (CT) characteristics have rarely been systematically described. A cohort of 27 patients with surgically resected CMPT were identified. Clinical and demographic features were recorded. Preoperative CT images of the CMPTs and the corresponding histopathological basis were also retrospectively analyzed. All of the tumors appeared as solitary nodules. Pure ground glass, part-solid nodules and solid nodules were detected in 2/27 (7.4%), 17/27 (63.0%), and 8/27 (29.6%) patients, respectively. Twenty-one tumors (77.8%) were located in the lower lobe. The average tumor size was 1.21±0.74 (range, 0.44-3.46) cm. Eighteen (66.7%) of the 27 patients had tumors with well-defined margins and lobulated contours. Fifteen patients (55.6%) had air bronchograms in the tumor, and 19 patients (70.4%) had air-containing space. There were two patients whose tumor size was enlarged and accompanied by an increase in solid components, and one patient simply had an increase in tumor size at the preoperative follow-up duration. Notably, one patient with solid tumor components was finally diagnosed with CMPT accompanied by adenocarcinoma. CMPTs of the lung mostly manifest as solitary, lobulated, well-defined tumors with air-containing spaces on CT and often occur in the periphery of the pulmonary lower lobe. When CT findings meet these criteria, the possibility of CMPT should be considered. Additionally, CMPT can coexist with adenocarcinoma. Further investigation will contribute significantly to the biological properties of CMPT and its relationship to the potential for malignant transformation.

Follicular Thyroid Adenoma with Papillary Architecture

A 23-year-old woman underwent left thyroid lobectomy and isthmusectomy for a 2 cm diameter firm mass on the left side of the neck that was also visualized on ultrasonography. The specimen consisted of a 22-gram thyroid gland composed of the left lobe, isthmus and a pyramidal lobe. Cut section of the left lobe showed a 3.5 cm diameter solitary, discrete and encapsulated mass with a tan lobulated and solid cut surface. The rest of the thyroid tissues had red-brown meaty cut surfaces.&#x0D; Microscopic section shows a follicular-patterned proliferation enclosed by a thin fibrous capsule with frequent Sanderson polster-like papillary excrescences. (Figures 1 and 2) Both the follicular and the papillary structures are lined by cuboidal to columnar follicular epithelial cells that had ample eosinophilic to pale cytoplasm and uniformly sized, minimally enlarged, generally round, and monolayered nuclei without nuclear grooving, folds, pseudoinclusions, and chromatin clearing. There are no mitotic figures seen. Some of the papillary structures have delicate vascular cores. (Figure 3) There are no psammoma bodies noted. The follicles contain variable amounts of pale eosinophilic colloid ranging from colloid-poor crowded follicles to those with ample colloid that have frequent peripheral scalloping. (Figure 4) Exhaustive sections failed to disclose capsular or vascular invasion. Based on the microscopic features, a diagnosis of follicular adenoma with papillary architecture was rendered.

Brunner’s gland hyperplasia as a cause of gastric outlet obstruction in a seven year old boy

Link of Video Abstract: https://youtu.be/9-ynkRS_wo8 Introduction: Brunner’s glands are acinotubular glands which are located mostly in the deep mucosal or submocosal layers of the proximal duodenum. Hyperplasia of these glands is reported in almost 1 in 50 upper gastrointestinal endoscopies and accounts for approximately 5 to 10 percent of all benign duodenal tumors. Brunner’s gland hyperplasia is usually asymptomatic. It can take form of polypoid or mass lesions and precipitate pyloric obstruction, gastrointestinal hemorrhage, and intussusception in children. Due to its rarity in pediatric population, it tends to be misdiagnosed. Case Description: This case report presents a case of seven year old boy with Brunner’s gland hyperplasia presented with recurrent vomiting. A seven year-old boy was admitted to the hospital due to of worsening of intractable vomiting since five months prior to admission. He also felt abdominal discomfort, bloating, and early satiety since he was 3 years old. The patient had been treated with several medications without significant improvement. Epigastric pain was observed on abdominal palpation. Gastroscopy showed partial gastric outlet obstruction (pyloric obstruction), erosive gastritis, multiple ulcers, and erosive esophagitis. Histopatologic results from biopsy revealed chronic gastritis and positive for Helicobacter pylori. Abdominal CT scan showed protrusion solid lesion intraluminal with diameter 1.18 x 1 x 1.25 cm in part II duodenum. Patient was consulted to pediatric surgeon for laparotomy exploration and duodeno-duodenostomy. Excision of Brunner’s gland dan biopsy were performed. Surgical report showed gastric dilatation with duodenal wall hypertrophy on part I-II of duodenum. Histopathological from biopsy revealed Brunner’s gland hyperplasia with lymphoid tissue. Post surgery patient recovered well and eventually discharged without any complains. The prognosis was good. Conclusion: Generally, Brunner’s gland hypertrophy is benign and has a good prognosis. However, with the growth of benign proliferative lesions of Brunner’s glands, mucosal ulcers may develop, thereby leading to the repair of gastric foveolar metaplasia with papillary architecture and then malignant transformation.

Well-Differentiated Papillary Mesothelial Tumor: An Unusual Radiologic Presentation: A Case Report

Well-differentiated papillary mesothelial tumor (WDPMT) is an uncommon tumor, formerly named well-differentiated papillary mesothelioma in the 2015 World Health Organization classification. It has a characteristic papillary architecture, bland cytologic features, a tendency toward superficial spread without invasion, and a good prognosis due to its clinically indolent behavior with prolonged survival. Rare cases with superficial invasion are termed WDPMT with invasive foci. WDPMT occurs primarily in the peritoneum of reproductive-age women, but also rarely in the pleura. We report a case of a 60-year-old woman who developed WDPMT with minimal invasion in the pleura with atypical radiological features and a family history of mesothelioma and indirect asbestos exposure.

Multidisciplinary management in the treatment of intrahepatic cholangiocarcinoma.

Multidisciplinary management in the treatment of intrahepatic cholangiocarcinoma.

Exploration of Morphological Features of Clear Cell Renal Cell Carcinoma With PBRM1, SETD2, BAP1, or KDM5C Mutations.

The last decade has seen great advances in genomic profiling and prognosis-associated factors of clear cell renal cell carcinoma (RCC), the most common entity in kidney cancer. Following VHL, PBRM1, SETD2, BAP1, and KDM5C have been validated as the most common co-occurring gene mutations in clear cell RCC by multicenter studies. However, the morphological features of clear cell RCC with co-occurring gene mutations remain unclear. In this study, we presented 20 clear cell RCCs that underwent next-generation sequencing, of which 1 tumor was reclassified as ELOC-mutated RCC. PBRM1, SETD2, BAP1, and KDM5C were the most common mutations, following VHL. Morphologically, clear cell RCC with PBRM1 or KDM5C mutation usually displayed a low-grade pattern. Cystic changes and hyalinized stroma were often observed. The Ki67 index was <10%. These observations indicated good prognosis. However, mutated SETD2 may increase the malignancy of clear cell RCC with PBRM1 mutation. Two clear cell RCCs with mutated PBRM1 and SETD2 developed local or distant metastases. Clear cell RCC with BAP1 mutations always had high-grade patterns, and rhabdoid differentiation was also observed, indicating that BAP1 mutation was associated with poor outcomes. Papillary architecture was often a feature of BAP1 mutation, which is uncommon in clear cell RCC. PDL1 was positive in only one tumor with BAP1 mutation, and the positivity rate was limited to 5%. B7H3 was negative in all tumors. Morphologic findings in this small cohort may suggest why PBRM1 mutation does not correlate with decreased survival, whereas BAP1 mutation usually predicts poor outcomes.

Two distinct pathogenic pathways of digital papillary adenocarcinoma - BRAF mutation or low-risk HPV infection.

Digital papillary adenocarcinoma (DPA) is a rare neoplasm that can exhibit local recurrence and distant metastasis. We present a series of eight cases of DPA showing two distinct clinical presentations, morphologies, immunophenotypes, and molecular features. Four cases were characterized by painless, slow-growing nodules located on the digits. The lesions were small, well-defined, and confined in the dermis. Histopathologically, these tumors were composed of glandular structures lined by cuboidal epithelium with luminal papillary infoldings. Only rare mitotic figures and minimal squamoid differentiation were present, and cellular necrosis was absent. All four cases were positive for the BRAF V600E immunohistochemistry but negative for p16, low-risk and high-risk HPV in situ hybridization (ISH). In contrast, the remaining four cases were characterized by painful, rapidly growing masses on the digits. These four lesions were located in the deep dermis and consisted of a solid, tightly packed papillary architecture lined by atypical epithelioid cells with inconspicuous nucleoli. Cellular necrosis, numerous mitotic figures, and prominent squamoid differentiation were seen. All cases were negative for the BRAF V600E IHC. However, they showed strong, patchy to diffuse reactivity for p16 and were positive for low-risk HPV ISH and negative for high-risk HPV ISH. Our findings suggest that the current classification of DPA encompasses tumors that show two discrete pathogenic pathways - BRAF mutation or low-risk HPV infection. DPAs with low-risk HPV infection exhibit aggressive clinical features, high-grade morphology, marked squamoid differentiation, and wild-type BRAF. DPAs with BRAF V600E have less aggressive clinical features, low-grade morphologic findings, mild to absent squamoid differentiation, and negative HPV infection.

The cytologic diagnosis of mesothelioma: are we there yet?

Mesothelioma is a rare but highly aggressive malignancy with poor prognosis that frequently present with recurrent effusions. Establishing the diagnosis by cytology can lead to early diagnosis and treatment and consequently improve prognosis. This review examines the cytological diagnosis of mesothelioma in the context of its historical and morphologic evolution and provides an update of the current reporting systems. Clues to identify the mesothelial and malignant nature of the sample are detailed as well as the supporting ancillary tests. Cytologically, the samples are overwhelmingly cellular and malignancy is recognized by both architectural and cytological atypia. Numerous variably sized clusters and enlarged cells are easily identified, some with papillary architecture and collagen cores. Recognizing the mesothelial nature of the cells and supportive immunostains are essential to rule out the differential diagnosis of metastatic carcinomas and reactive mesothelium. Current ancillary tests such as homozygous deletion of CDKN2A, loss of BRCA1-associated protein, and methylthioadenosine phosphorylase expression can provide further support of malignancy. At this time with the aid of current ancillary tests and in the hands of cytopathologists with adequate experience with the interpretation of effusions, the diagnosis of mesothelioma can be established with accuracy in most cases.

The Presence of Typical "BRAFV600E-Like" Atypia in Papillary Thyroid Carcinoma is Highly Specific for the Presence of the BRAFV600E Mutation.

Papillary thyroid carcinomas (PTCs) are driven by a variety of molecular abnormalities including BRAF, RAS, ALK, RET, and NTRK alterations. PTCs driven by the BRAFV600E mutation, or tumours which demonstrate a similar gene expression profile to PTCs driven by this mutation, have been reported to demonstrate specific morphological features sometimes termed "BRAFV600E-like" atypia. BRAFV600E-like atypia is characterised by a well-developed papillary architecture, infiltrative growth, marked nuclear clearing, prominent intranuclear pseudoinclusions, abundant eosinophilic cytoplasm, and scattered psammoma bodies. We sought to investigate the sensitivity and specificity of these morphological features for the presence of BRAFV600E mutation in PTCs as determined by mutation specific immunohistochemistry. An unselected cohort of 495 PTCs was reviewed by a single pathologist and categorised into three groups: typical BRAFV600E-like atypia (145 cases, 29%), possible BRAFV600E-like atypia (166 cases, 33%) and little/no BRAFV600E-like atypia (184 cases, 37%). The specificity and sensitivity of typical BRAFV600E-like atypia for the BRAFV600E mutation was 97.2% and 44.3%, respectively. When typical and possible BRAFV600E-like atypia were analysed together, the specificity was 70.6% and the sensitivity was 81.7%. In the morphologically little/no BRAFV600E-like atypia group, 58 cases (31.5%) had a BRAFV600E mutation. We conclude that typical BRAFV600E-like atypia is highly specific for the presence of the BRAFV600E mutation; however, the absence of BRAFV600E-like atypia does not exclude this mutation.

Primary cutaneous endocrine mucin-producing sweat gland carcinoma: a rare case report

Background: Endocrine mucin-producing carcinoma is a rare adnexal tumour of the skin with low-grade cytological features and neuroendocrine differentiation. It has a predilection for skin of the eyelid, but has also been reported in the face and rarely extra-facial locations. The tumour is seen more frequently in women affecting the elderly. It is histologically and immunohistochemically analogous to solid papillary carcinoma of breast/ductal carcinoma in situ with nodular, solid, papillary, and /or cribriform architecture, neuroendocrine differentiation and mucin production with preserved myoepithelial cell layer.

Malignant Meningioma: Two Cases Observed at the Hospital Center of Soavinandriana, Antananarivo

Introduction: Meningiomas are tumors formed by arachnoid cells, typically attached to the inner surface of the dura mater. Malignant forms are rare and no case has been reported in the Malagasy literature. The objective of our study is to report two Malagasy cases of malignant meningioma and to discuss the epidemiological and anatomical-clinical particularities of this tumor. Observation: The first patient, a 41-year-old woman, presented with a rapidly progressive intracranial hypertension syndrome. The patient had undergone surgery two years earlier for a grade II meningioma and had no family history of meningioma, neurofibromatosis, or personal history of brain irradiation or head trauma. Her brain scan showed a heterogeneous polylobed left parieto-occipital mass with a meningeal implantation base. The anatomopathological examination of the samples revealed a malignant meningioma. The second patient was a 33-year-old man, operated for grade I meningioma eleven months before admission, with no other personal or family history. The patient was hospitalized for tumor recurrence with signs of intracranial hypertension. The brain computed tomography (CT) scan showed a heterogeneous extra-axial tumor in right temporo-parietal lobe. Surgical excision was performed. On histological examination, a proliferation of tumor cells of meningothelial appearance with papillary architecture was observed, leading to the diagnosis of malignant meningioma. Conclusion: Malignant meningioma is a rare and serious entity. The clinical manifestations are nonspecific and imaging may mimic a low-grade meningioma. The diagnosis of certainty is histological and is based on essentially morphological criteria. The latter condition the overall survival of the patient and the therapeutic conduct.

Challenges in Risk Stratification of Solid Atypical Mixed Echogenicity Thyroid Nodules.

Background: To determine the prevalence and risk of malignancy (ROM) in solid atypical mixed echogenicity thyroid nodules (SAMENs) with sonographic patterns not classifiable by the 2015 American Thyroid Association Ultrasound Risk Stratification System (NC ATA). Methods: We searched our prospectively collected endocrine surgery thyroid nodule (TN) database, with particular attention to those solid nodules that were NC ATA. An algorithm assigned each into one of the five ATA risk groups per the 2015 American Thyroid Association Ultrasound Risk Stratification System (ATA USRSS). TNs that the algorithm could not assign to a risk group were deemed NC ATA and were subsequently analyzed. Additionally, we categorized this group using an algorithm based on the 2017 American College of Radiology Thyroid Imaging Reporting and Data System (ACR-TIRADS). We were specifically interested in the characteristics that resulted in non-classification by the 2015 ATA USRSS and the fine needle aspiration biopsy (FNAB) cytology and surgical pathology results from the group. Results: We evaluated data from 5,040 nodules, of which 1,772 had surgical pathology. There were 150 solid nodules not classified by 2015 ATA USRSS, all of which demonstrated atypical features along with iso-, hetero-, hyper-and mixed echogenicity (solid atypical mixed echogenicity nodules-SAMENs). Sixty of these nodules were excised and sent for surgical pathology, while 90 were followed without surgical excision. Out of the 90 that did not undergo surgery, 82 underwent FNAB with cytologic evaluation. Of our 150 SAMENs, 40 were malignant by surgical histology and six were likely malignant by cytology (total SAMEN ROM without noninvasive follicular thyroid neoplasm with papillary-l ike nuclear features 31%). The most common sonographic pattern present in our SAMEN group consisted of an isoechoic solid component with microcalcifications (28/40-70% of all excised malignant nodules). In our excised malignant SAMENs, 50% demonstrated follicular-patterned neoplastic architecture while 48% displayed papillary architecture. Conclusion: Our study demonstrates that SAMENs with at least one suspicious sonographic feature: including (1) microcalcifications; (2) irregular or other suspicious margins,;opulation, and a higher ROM (31%) than the intermediate-risk group of the 2015 ATA USRSS (10-20%).