Psammoma Research Articles

Psammomatous calcifications in thyroid oncocytic (Hürthle cell) follicular tumors

Concentric calcifications, also known as psammoma bodies, are a relatively frequent finding in certain types of tumors, particularly papillary thyroid carcinoma (PTC). In the thyroid, they have been assigned a significant role in the diagnosis of PTC and in distinguishing between these tumors and other types of thyroid neoplasms. Concentric calcifications have also less commonly been noted in other processes in the thyroid, such as in tumors characterized by cells containing abundant oxyphilic cytoplasm (i.e., Hürthle cells). We have studied 12 patients with oncocytic thyroid follicular tumors that contained scattered psammomatous calcifications that led to difficulties in diagnosis. The patients were 9 women and 3 men, aged 34 to 63 years. 10 cases corresponded to benign, non-invasive oncocytic tumors and 2 cases were minimally invasive follicular carcinomas of oncocytic (so called Hürthle cell) type. The psammomatous calcifications were randomly scattered throughout the lesions and were present as a focal, incidental finding in 8 cases and were diffuse in 4 cases. They were composed of concentrically laminated deposits of dense basophilic material closely resembling psammoma bodies, often associated with more homogeneous deposits of lightly eosinophilic material without concentric lamination that were interpreted as precipitated thyroglobulin. Seven patients with clinical follow-up, including one with minimally invasive carcinoma, were alive and well between 5 and 12 years after diagnosis. Concentric laminated calcifications may be encountered in oncocytic (Hürthle cell) follicular tumors and should not be interpreted as indicative of PTC in the context of oncocytic neoplasms of the thyroid.

A para-aortic malignant melanotic nerve sheath tumor mimicking a gastrointestinal stromal tumor: a rare case report and review of literature

BackgroundMalignant melanotic nerve sheath tumor (MMNST), formerly called melanotic schwannoma, is a rare tumor of neural crest derivation which most frequently arises from the region of spinal or autonomic nerves near the midline. Recent studies have reported malignant behavior of MMNST, and there still has no standard management guidelines. Intra-abdominal MMNST, which has never been reviewed as an entity, is even rarer. In this study, we present a rare case of a cystic MMNST arising from the para-aortic region and mimicking an intra-abdominal gastrointestinal stromal tumor (GIST), and review the literature regarding MMNSTs located in the abdominal cavity.Case presentationA 59-year-old female was incidentally found a tumor located in the left para-aortic area by non-contrast computed tomography. A Magnetic Resonance Imaging showed a cystic mass originated from the inferior mesenteric artery (IMA) territory. A GIST was initially diagnosed. The tumor was resected en bloc by laparoscopic surgery and was found between mesocolon and Gerota’s fascia with blood supply of IMA. Grossly, dark brown materials were noted at the inner surface of the cystic wall. Microscopically, the tumor cells were melanin-containing, and no psammomatous bodies were present. Immunohistochemically, the tumor showed positivity for MART1, HMB45, collagen IV, and SOX10, and negativity for AE1/AE3. MMNST was favored over malignant melanoma, since the tumor was located near ganglia and had cells with less atypical cytology and a low mitotic rate, and subsequent adjuvant radiotherapy was performed. The patient was alive with no evidence of recurrent or metastatic disease 11 months after radiotherapy.ConclusionsOur review of abdominal MMNST cases showed a female predominance, with an average age of 54.8 years, and a trend toward being a larger tumor showing cystic or necrotic changes. Local recurrence and metastasis rate were reviewed, and both showed a low rate. Diagnosis of MMNST should combine all the available findings, and complete excision of the tumor should be performed, followed by long-term patient monitoring.

Malignant psammomatous melanotic schwannoma mimicking adrenal cyst: case report

BackgroundMelanotic schwannoma is a melanin producing nerve sheath tumors. Rarely, it can be associated with psammoma bodies, called psammomatous melanotic schwannoma. Psammomatous melanotic schwannomas are associated in up to 10% of the cases with Carney’s syndrome. The rarity of the lesion, which may present at different localizations create difficulty in placing a correct initial diagnosis. Definitive diagnosis is made after complete tumor excision and pathomorphological evaluation. The prognosis depends on the anatomical localization, local invasion and presence of a high mitotic index. The main pathomorphological differential diagnosis includes schwannomas and other melanin producing tumors as melanoma.Case presentationWe present a case of an 11-year-old female with cystic lesion adjacent to right adrenal gland, mimicking adrenal cyst. Ultrasound guided biopsy was undertaken due to the cystic appearance of the formation and the lack of certain diagnosis from the non-invasive diagnostic tests. No signs of cellular and nuclear atypism were observed. The diagnosis of benign endothelial cyst with spontaneous hemorrhage was suggested. The patient underwent transabdominal laparoscopic adrenalectomy en-bloc with the cyst to prevent spillage of the cyst content due to the intimate adhesion of the lesion to the adrenal gland and vena cava inferior. Pathomorphological examination revealed malignant psammomatous melanotic schwannoma. The adrenal gland was intact with no tumor infiltration. The patient was followed up on the 1st and 2nd month afterwards the surgery by MRI with no signs of local recurrence and postoperative complications.ConclusionPsammomatous melanotic schwannoma near adrenal gland are rare and present difficulty with exact preoperative diagnosis. Complete resection should always be provided. Laparoscopic surgery is feasible if radical excision is not compromised. Long-term follow-up and Carney’s syndrome surveillance after complete excision are recommended especially in young patients.

Anaplastic Pleomorphic Xanthoastrocytoma versus Pleomorphic Xanthoastrocytoma

Pleomorphic xanthoastrocytoma (PXA), WHO grade II, is a rare entity accounting for <1% of all astrocytic tumors. It affects children and young adults and is commonly found in the temporal lobe. Anaplastic PXA (APXA) has a similar location and clinical manifestation as that of PXA but has a significantly worse prognosis than the latter. WHO 2016 defined PXA as having >5/10 HPF mitosis and with or without necrosis as APXA (grade III). Herein, we present two such cases with unusual locations and ages: (1) APXA inside lateral ventricle, in a 10-year-old female child and (2) PXA in a 39-year adult male. Histologically, both cases revealed a tumor comprised a highly pleomorphic heterogeneous population of cells, eosinophilic granular bodies, and psammoma bodies, however, necrosis and increased mitosis (>5/10 HPF) were appreciated only in the first case. Immunohistochemistry is supported by strongly positive glial fibrillary acidic protein, vimentin, and synaptophysin. This study analyzed all the characteristics of both these entities with their unusual presentations to prevent future misdiagnoses.

Cytologic presentation and clinicopathologic correlation of Mullerian carcinosarcoma on serous fluid samples.

Limited data are present to study the cytologic findings of Mullerian carcinosarcoma (MCS) in serous fluid samples and clinicopathologic features that are associated with cytology yield. We studied 30 MCS patients diagnosed on surgical resection samples, and reviewed their cytomorphology and immunophenotypes on concurrent serous fluid cytology samples. Clinicopathologic features were also compared between cases with positive or negative cytology. Fourteen out of 30 patients showed positive cytology, including 12 patients with only carcinomatous components and 2 with sarcomatous cells. Cytomorphology of MCS was mostly consistent with adenocarcinoma, with psammoma bodies occasionally present. The 2 cases with sarcomatous cells showed spindle cells without signs of heterologous differentiation. PAX8 was positive in 10 of 11 cases, and WT1 was positive in 8 of 11 cases including the case with negative PAX8. In 1 case, PAX8 and WT1 were only positive in the sarcomatous but not in carcinomatous cells. MOC31 showed consistent positivity in carcinomatous cells, which appeared to be more sensitive than B72.3 (positive in 72.7%). In addition, sarcomatous cells showed CD10 positivity in 1 case. Clinically, patients who developed body cavity effusions or with higher stage diseases were more likely to have positive cytology. Cytologic diagnosis of MCS in the serous fluid is challenging due to the rare presence of sarcomatous component. Staining both PAX8 and WT1 is recommended to confirm their Mullerian origin, although both markers may be positive only in sarcomatous cells. Cytology yield of MCS is highly associated with the disease stage.

Liesegang rings in the setting of end‐stage renal disease

Liesegang rings are acellular, lamellar, concentric rings of organic or inorganic material naturally formed in both biologic and environmental systems. Description in human tissue is scarce. Liesegang rings have exclusively been identified in association with pathologic disease processes and thus are not typically considered in differential diagnosis. They are usually described with cystic or inflammatory lesions. Histologically, Liesegang rings show features that are also seen in sections of parasitic ova, larvae, psammoma bodies, and by radiology as calcifications in cystic diseases of the breast and kidney. We noted at autopsy of a 59-year-old diabetic woman multiple black "stones" in the renal medulla. Microscopic examination demonstrated these to contain Liesegang rings. Liesegang rings formation should be considered in the differential diagnosis of atypical appearing deposits in the kidneys and other tissues. They may play a role in the pathogenesis of kidney stones.

Case Report: Fortuitous discovery of primary peritoneal psammocarcinoma

Psammocarcinoma is an uncommon subtype of low-grade serous carcinoma. It is characterized by the presence of extensive psammoma bodies and can have either an ovarian or peritoneal origin. To our knowledge fewer than 30 cases of primary peritoneal psammocarcinoma (PPP) have been reported in the English literature. We report a rare case of PPP in a 74-year-old female, discovered fortuitously within a laparotomy for gallbladder lithiasis. At laparotomy, multiple nodular implants involving the omentum, the peritoneum and a magma of intestinal loops in the right iliac fossa were noted. A biopsy from nodules was performed. Gross examination showed multiple nodules of different sizes in the fat tissue. Pathologic examination showed massive psammoma bodies representing more than 75% of the tumor. The final diagnosis was psammocarcinoma. Our patient was referred to the gynecologic department for further investigation and to ascertain whether the tumor arose from the ovaries or peritoneum. Hysterectomy, bilateral adnexectomy and omentectomy were performed. Macroscopic examination showed that both ovaries were intact having a normal size. No invasion of ovarian stroma was shown in microscopic examination. The patient died of SARS-CoV-2 (COVID-19) six days after the surgery. PPP is a rare type of low-grade serous carcinoma. The behavior of this tumor is unclear, and the treatment is not standardized because of its rarity and lack of long-term follow-up. More cases need to be studied for better understanding and improvement of the management protocols.

Serous cavity metastasis: Evaluation of unknown primary.

Malignant effusions can occur in patients with neoplasia. Once a metastatic diagnosis is confirmed, the primary site of origin of malignancy needs to be ascertained. This task can be challenging without a prior history of malignancy. In some patients their effusion may be the initial presentation of an underlying malignancy. Metastases usually present with a dual population of mesothelial and malignant cells. Combining cytomorphologic examination with ancillary testing such as immunocytochemistry can help identify the origin of the foreign malignant cell population. Helpful architectural clues include a single cell pattern, solid cell ball pattern, single file arrangement, papillary formation, psammoma bodies and background mucin. Useful cellular features include the presence of signet ring cells, small cells, pleomorphic and multinucleated giant cells, squamous cells, spindle cells and pigmentation. Rarely, despite an extensive work-up the primary site of origin for a malignant effusion may remain unresolved. This review article will be incorporated finally as one of the chapters in CMAS (CytoJournal Monograph/Atlas Series) #2. It is modified slightly from the chapter by the initial authors in the first edition of Cytopathologic Diagnosis of Serous Fluids.

Clinicopathological features of ectopic meningothelial hamartoma

Objective: To investigate the clinicopathological features, diagnosis and differential diagnosis of ectopic meningothelial hamartoma (EMH). Methods: Three cases of EMH diagnosed in the First Affiliated Hospital of Nanjing Medical University from January 2014 to December 2020 were enrolled. All cases were evaluated by clinical and imaging features, HE and immunohistochemical staining, and the relevant literature was reviewed. Results: There were one male and two female patients, aged 2, 67 and 19 years, respectively. Clinically, they presented as skin masses in the head and face region (two cases) and sacro-coccygeal region (one case). Grossly, the lesions ranged in size from 1.6 cm to 8.9 cm. Microscopically, the lesions were ill-defined, and located in the dermis and subcutis, and showed pseudovascular channels lined by monolayer of cuboidal to flattened epithelium with mild atypia, with variable cystic cavity formation. There was prominent interstitial fibrosis. Concentric, lamellated, onion skin-like arrangement with short spindle or ovoid cells and psammoma bodies were noted. Immunohistochemically, these cells were strongly positive for SSTR2, EMA, vimentin and progesterone receptor. Ki-67 positive index was low, approximately 1%. Conclusions: EMH is uncommon. Definitive diagnosis relies on histopathologic examination. The importance in recognizing the lesions is to differentiate from other more aggressive tumors.

Clinicopathological and molecular characterization of biphasic hyalinizing psammomatous renal cell carcinoma: further support for the newly proposed entity

The classification of renal neoplasms continues to evolve with novel, emerging, and provisional entities being described constantly. Biphasic hyalinizing psammomatous renal cell carcinoma (BHP RCC) associated with somatic NF2 mutations is one such new renal entity and is considered as a provisional category of RCC due to its very limited data. To provide further support for the newly proposed entity, we identified three additional cases of BHP RCC, with clinicopathological, immunohistochemical, and various molecular analyses. There were 2 males and 1 female, aged 65, 56, and 69 years, respectively. The neoplasms were unencapsulated, and all had a characteristic biphasic appearance of smaller cells clustering around basement membrane material within larger acini, forming pseudorosettes or a glomeruloid pattern. Hyalinized sclerotic stroma and psammoma bodies were abundant in two cases and focally present in one case. Focal areas of a less distinctive appearance were also noted; one additionally had an elongated tubular pattern in the myxoid stroma that is reminiscent of mucinous tubular and spindle cell carcinoma; one consisted solid alveolar architectures of epithelioid clear cells, bearing some resemblance to clear cell RCC. The neoplasms did not have a distinctive immunohistochemistry (IHC) profile, though all labeled for vimentin and CK7. Targeted DNA sequencing revealed that one case harbored a pathogenic somatic frameshift mutation in the NF2 gene, which was further confirmed by Sanger sequencing. The other two cases lacked NF2 mutations and instead demonstrated NF2 promoter methylation by methylation-specific polymerase chain reaction. Subsequent IHC assessment showed loss of expression of NF2 in all 3 cases, which evaluated NF2 status at the protein level. According to RNA sequencing-based clustering analysis, the 3 cases formed a distinct group with a shared specific transcriptional profile different from that of other established renal tumor types. In addition, phosphate inositide 3-kinase (PI3K)/AKT pathway was enriched significantly and on the top of all enriched pathways. Clinically, one patient developed bone metastases and died of disease two years after diagnosis. The other two patients had no evidence of recurrence or metastases, at 4- and 5-yearfollow-up. These findings not only validate previously described clinicopathological featuresbut also expand the potentially genetic alterations and available clinical outcome data.

Warthin like Variant of Papillary Thyroid Carcinoma: A Rare Variant

Introduction: Warthin like papillary thyroid carcinoma is a rare variant that bears features similar to Warthin tumour of salivary gland. It shows papillary or follicular structures lined by oncocytic cells having typical nuclear features of papillary thyroid carcinoma and marked lymphoplasmacytic infiltrate in the stroma. Case Report: A 60 year old lady presented in the ENT OPD with right sided neck swelling since 2 years. On examination the swelling was firm, non-tender, moving with deglutition and measured 4x3 cm. FNA smears of the swelling were highly cellular and comprised of cells arranged in papillary clusters. The cells were predominantly oncocytic and showed nuclear grooving and intranuclear inclusions. Cytological diagnosis of papillary thyroid carcinoma (Bethesda Category VI) was offered. Thyroidectomy specimen measured 6.5x5x3 cm and right lobe revealed gray tan tumor with numerous papillae and few cystic areas. Microscopy revealed a well circumscribed tumour, with tumour cells arranged in papillary architecture with presence of dense lymphoplasmacytic infiltrate in the stalks of papillae. The cells lining the papillae had abundant granular eosinophilic cytoplasm and many of the cells showed nuclear grooving and intranuclear inclusions. Occasional psammoma bodies were also seen. The surrounding thyroid showed features of hashimoto’s thyroiditis. A final diagnosis of Warthin like variant of papillary thyroid carcinoma was given. Conclusion: Warthin like variant of papillary thyroid carcinoma is a distinct rare variant. It is associated with good prognosis when compared with other variants of papillary thyroid carcinoma, warranting a proper identification.

Clinicopathological features of NTRK3 gene rearrangement papillary thyroid carcinoma

Objective: To investigate the clinicopathological features and differential diagnosis of NTRK3 gene rearrangement thyroid papillary carcinoma (PTC). Methods: The PTC cases without BRAF V600E mutation were collected at Fujian Provincial Hospital South Branch from January 2015 to January 2020. The cases of NTRK3 gene rearrangement PTC were examined using immunohistochemistry and fluorescence in situ hybridization (FISH). The clinical data, histopathological characteristics, immunohistochemical features and molecular pathological changes were retrospectively analyzed. Data from the TCGA PTC dataset and the literature were also studied. Results: A total of 3 PTC cases harboring NTRK3 gene rearrangement were confirmed. All the patients were female, aged from 26,49,34 years. Histologically, two of them demonstrated a multinodular growth pattern. Only one case showed prominent follicular growth pattern; the other two tumors showed a mixture of follicular, papillary and solid growth patterns. All tumors showed a typical PTC nuclear manifestation, with some nuclear pleomorphism, vacuolated foci and oncocytic features. The characteristic formation of glomeruloid follicular foci was present in two cases which also showed psammoma bodies, and tumoral capsular or angiolymphatic invasion. The background thyroid parenchyma showed chronic lymphocytic thyroiditis. Mitotic rates were low, and no cases had any tumor necrosis. The pan-TRK and TTF1 testing was both positive in 3 cases, while S-100 and mammaglobin were both negative in them. FISH studies confirmed the NTRK3 gene rearrangement in all 3 cases. Studies on the TCGA datasets and literature revealed similar findings. Conclusions: NTRK3 gene rearrangement PTC is rare. It may be easily misdiagnosed due to the lack of histological and clinicopathological characteristics. Molecular studies such as pan-TRK immunostaining, FISH and even next-generation sequencing are needed to confirm the diagnosis. Immunohistochemistry of pan-TRK performed in the PTC cases without BRAF V600E mutation can be used as a good rapid-screening tool. With the emergence of pan-cancer tyrosine receptor kinase inhibitors, proper diagnosis of these tumors can help determine appropriate treatments and improve their outcomes.

Multifocal Diffuse Sclerosing Papillary Thyroid Carcinoma: A Rare Variant with Diagnostic Challenges

Diffuse sclerosing papillary thyroid carcinoma (DS PTC) is a relatively rare variant of papillary thyroid carcinoma. It is characterized by distinct histological features like scattered microscopic tumor islands, diffuse sclerosis, lymphocytic infiltration, numerous psammoma bodies, radiological features like snowstorm appearance and biologically aggressive behavior in the form of invasion and metastasis. A preoperative diagnosis is often challenging in the absence of nodules and scanty fine needle aspiration cytology sample. We describe a case of multifocal diffuse sclerosing variant of papillary thyroid carcinoma in a 29 year old young male who presented with a swelling in the right side of neck of 2 month duration in the absence of a visible thyroid swelling. Neck swelling was non tender, well defined, firm, not moving with deglutition. Laboratory studies showed normal thyroid function, neck ultrasound revealed heteroechoic right lobe with multiple punctate echogenic foci and enlarged right sided cervical nodes with echogenic foci, fine needle aspiration cytology of which was consistent with metastasis from papillary adenocarcinoma. Based on the above investigations, a total thyroidectomy with central compartment lymph node dissection and modified radical neck dissection of right side was performed. Histological analysis revealed Multifocal Diffuse Sclerosing variant of papillary Thyroid Carcinoma. Clinical and histological challenges usually occur when DS PTC present as diffuse thyroid enlargement, dispersed microscopic tumor islands, extensive fibrosis, abundant lymphocytic infiltration mimicking thyroiditis and when the fine needle aspiration cytology sample is non representative.

AKT Isoforms Interplay in High-Grade Serous Ovarian Cancer Prognosis and Characterization.

Simple SummaryNew therapeutical strategies are needed to improve survival in high-grade serous ovarian cancer (HGSOC) patients. AKT inhibitors are promising agents able to act in synergy with PARP inhibitors and platinum-based therapies, but the subset of patients who could benefit from this approach is still unclear. We analyzed AKT isoforms expression in a retrospective cohort and we identified four AKT expression groups related to patients’ survival, tumor morphology and the BRCA status that could help in stratifying patients for future clinical trials.High-grade serous ovarian cancer (HGSOC) is among the deadliest gynecological malignancies. The acquired resistance to platinum-based therapies and the intrinsic heterogeneity of the disease contribute to the low survival rate. To improve patients’ outcomes, new combinatorial approaches able to target different tumor vulnerabilities and enhance the efficacy of the current therapies are required. AKT inhibitors are promising antineoplastic agents able to act in synergy with PARP inhibitors, but the spectrum of patients who can benefit from this combination is unclear, since the role of the three different isoforms of AKT is still unknown. Here, we study the expression of AKT isoforms on a retrospective cohort of archive tissue by RT-droplet digital PCR (ddPCR) analyzing their association with the clinicopathological features of patients. Based on AKT1/AKT2 and AKT1/AKT3 ratios, we define four AKT classes which were related to patients’ survival, tumor morphology and BRCA1 expression. Moreover, our results show that high AKT3 expression levels were frequently associated with tumors having classic features, a low number of mitoses and the presence of psammoma bodies. Overall, our study obtains new insights on AKT isoforms and their associations with the clinicopathological features of HGSOC patients. These evidences could help to better define the subsets of patients who can benefit from AKT and PARP inhibitors therapy in future clinical trials.

Non-tumoral Psammoma Bodies Correlate With Adverse Histology in Classic Type Papillary Thyroid Carcinoma

Psammoma bodies are a characteristic of papillary thyroid carcinoma. The prognostic value of thyroid psammoma bodies, however, has not been clarified. The authors conducted this study to ascertain whether non-tumoral psammoma bodies are associated with undesirable histological findings. A study of 584 cases discovered that non-tumoral psammoma bodies were associated with extensive lymphatic spread and more aggressive tumor growth in classic type papillary thyroid carcinoma. As recommended by the authors, it is crucial to mention the presence of psammoma bodies in the pathology report.

BIBLIOMETRIC ANALYSIS OF THE SCIENTIFIC LITERATURE ON MENINGIOMAS WITH CALCIFICATION

Meningiomas are the most common non-glial tumours of the central nervous system characterized by pathological biomineralization. The work aimed to conduct bibliometric analysis and systematize data on the prevalence, etiology, morphology and main trends in the study of meningiomas with calcification. The authors searched for information on meningiomas in electronic databases such as PubMed, Scopus, Web of Science and Google Scholar for the past 25 years by the key terms such as meningiomas, calcifications, and psammoma bodies. For bibliometric analysis, the authors used an online platform to monitor and analyze international research using visualization tools and modern citation metrics SciVal (Scopus) and a tool for building and visualizing bibliometric networks VOSviewer. Pathological biomineralization is manifested through the formation of psammoma bodies, and the main mineral component is calcium hydroxyapatite. Although calcification is likely to play a protective role and be a favourable prognostic feature, it should be considered when choosing surgical tactics. There is also the problem of closing the defects of the dura mater with the help of biological and synthetic transplants. According to the bibliometric analysis of scientific literature on meningiomas and the phenomena of pathological biomineralization in them, we found that the number of publications on this topic had increased significantly over the past five years, the leading countries of origin are the United States, Japan and China. When researching the array of Scopus database publications using SciVal tools, the problem of meningioma calcification was divided into 61 topics and 24 thematic clusters, the vast majority of which belonged to medicine and biology and materials science. According to the results of bibliometric analysis of 678 publications in the Scopus database by keywords "calcification" and "meningioma", they can be divided into seven thematic clusters and four chronological stages. Despite the prevalence of meningioma calcification, there is currently no fundamental idea of ​​the etiology and pathogenesis of this process. Studying the morphological features of meningiomas with calcification can help improve the diagnosis and treatment of the central nervous system tumours.

Spectrum of biphasic renal cell carcinomas with hyalinized stroma and psammoma bodies associated and not associated with NF2 alteration

A unique subtype of biphasic renal cell carcinoma (RCC) was recently described and termed biphasic hyalinizing psammomatous RCC (BHPRCC). This tumor shows a dual population of larger cells and small cells surrounding basement membrane-like materials and invariably has papillary features, hyalinized stroma, and psammoma calcifications. The biphasic pattern in BHPRCC may resemble that of RCC associated with TFEB gene fusion or t (6;11) RCC. However, all reported BHPRCCs had no TFEB alterations and all were associated with neurofibromin 2 (NF2) mutations. Herein, we present three biphasic RCCs encompassing the reported BHPRCC morphologies. One RCC showed solid, nested, papillary, and tubular growths, with biphasic pattern of larger cells surrounding clusters of smaller cells arranged around basement membrane-like materials, and harbored NF2 mutation consistent with BHPRCC. This patient developed bone metastasis 59 months after surgery. The two other biphasic RCCs showed morphologic overlap to BHPRCC, but in addition had other features not seen in BHPRCC, such as lack of papillary pattern, having large tubules containing mucinous to collagenous spherules (mucicarmine and collagen IV positive) bordered by a single layer of small cells with occasional central targetoidpsammoma bodies, and with widespread nuclear grooves. Interestingly, these two tumors also did not show alterations in NF2 or TFEB including translocation or amplification. In conclusion, we report another example of the novel BHPRCC that had metastasized and two biphasic RCCs not associated with NF2 or TFEB alterations; the latter two shared additional distinct morphological features and may represent a unique biphasic RCC distinct from the novel BHPRCC.

Non-Invasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features Is Not a Cytological Diagnosis, but It Influences Cytological Diagnosis Outcomes: A Systematic Review and Meta-Analysis

Background: A low-risk thyroid tumour, non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) was introduced in 2016. NIFTP criteria require a thorough histological examination to rule out capsular and lymphovascular invasion, which denies the possibility of preoperative cytological diagnosis. Nevertheless, since the adoption of the new entity, the cytology of NIFTP has been a subject of interest. Objectives: The present systematic review and meta-analysis investigate the cytological diagnosis of NIFTP. Method: An online PubMed literature search was conducted between March 1, 2020, and June 30, 2020, for all original articles considering the cytology of histologically proven NIFTP. The studies including data on fine needle aspiration specimens classified by The Bethesda System for Reporting Thyroid Cytology (TBSRTC) categories, risk of malignancy (ROMs) in the TBSRTC categories, and cytomorphological features of NIFTP were included in the meta-analysis. Non-English studies and case reports were excluded. The data were tabulated and statistical analysis was performed with Open Meta-Analyst program. Results: Fifty-eight studies with a total of 2,553 NIFTP cases were included in the study. The pooled prevalence of NIFTP cases was calculated among 25,892 surgically resected cases from 20 studies and the results show that NIFTP consisted 4.4% (95% confidence interval [CI]: 3.5–5.4%) of all cases. Most of the NIFTP cases (79.0%) belonged to the intermediate categories of TBSRTC. The pooled distribution of NIFTP cases in each TBSRTC category was 1.3% (95% CI: 0.8–1.7%) in non-diagnostic (ND), 8.9% (95% CI: 6.9–10.8%) in benign, 29.2% (95% CI: 25.0–33.4%) in atypia of undetermined significance or follicular lesion of undetermined significance (AUS/FLUS), 24.2% (95% CI: 19.6–28.9%) in follicular neoplasm (FN), 19.5% (95% CI: 16.1–22.9%) in suspicious for malignancy (SM), and 6.9% (95% CI: 5.2–8.7%) in malignant. Compared to pre-NIFTP era, the pooled risk differences of ROM were reduced by 2.4% in ND, 2.7% in benign, 8.2% in AUS/FLUS, 8.2% in FN, 7.3% in SM, and 1.1% in the malignant category. The cytomorphological features of NIFTP were similar to follicular variant of papillary thyroid carcinoma (FVPTC) but lesser to papillary thyroid carcinoma (PTC). Conclusions: Based on our results, NIFTP remains a histological diagnosis. Although cytomorphological features cannot be used in differentiating NIFTP from FVPTC, they may guide in separating NIFTP from PTC. Features such as papillae, microfollicles, giant cells, psammoma bodies, and the amount of papillary-like nuclear features should be taken into account when suspicious of NIFTP. NIFTP should not have papillae or psammoma bodies, and giant cells were rarely observed.

Type I cutaneous meningioma of dorsal thoracic spine (Rudimentary Meningocele): A rare entity at an unusual site

Cutaneous meningiomas (CM) are rare variants of meningiomas which are further classified into three subtypes. Type I CM (TICM) or Rudimentary meningocele (RM) is an uncommon developmental anomaly in which meningothelial elements are displaced into the skin and soft tissue. We present a case of 11 year boy with an upper back swelling since early childhood. His MRI spine showed a lesion at T4-T7 level with a fistulous tract connecting it to dural sac. Histopathology revealed clusters of oval to spindle cells arranged in whorls amidst collagen bundles and psammoma bodies. On immunohistochemistry these cells expressed EMA and Vimentin. A diagnosis of TICM was rendered based on these characteristic clinico-radiological & histopathological features. TICM pose a diagnostic challenge clinically and histopathologically and have an excellent prognosis. This is the 4 Indian case of RM and the 1 case of RM to be located in the spine in the Indian literature.

Translocation carcinomas of the kidney.

The MiT subfamily of transcription factors includes TFE3, TFEB, TFEC, and MITF. Gene fusions involving two of these transcription factors have been well-characterized in renal cell carcinoma (RCC). The TFE3-rearranged RCC (also known as Xp11 translocation RCC) was first officially recognized in the 2004 World Health Organization (WHO) renal tumor classification. The TFEB-rearranged RCC, which typically harbor a t(6;11)(p21;q12) translocation which results in a MALAT1-TFEB gene fusion, were first officially recognized in the 2016 WHO renal tumor classification. These two subtypes of translocation RCC have many similarities. Both disproportionately involve young patients, although adult translocation RCC overall outnumber pediatric cases. Both often have unusual and distinctive morphologies; the TFE3-rearranged RCCs frequently have clear cells with papillary architecture and abundant psammoma bodies, while the TFEB-rearranged RCCs frequently have a biphasic appearance with both small and large epithelioid cells and nodules of basement membrane material. However, the morphology of these two neoplasms can overlap, with one mimicking the other or other more common renal neoplasms. Both of these RCC underexpress epithelial immunohistochemical markers, such as cytokeratin and epithelial membrane antigen, relative to most other RCC. Unlike other RCC, both frequently express the cysteine protease cathepsin k and often express melanocytic markers like HMB45 and Melan A. Finally, TFE3 and TFEB have overlapping functional activity as these two transcription factors frequently heterodimerize and bind to the same targets. Therefore, these two neoplasms are now grouped together under the heading of "MiT family translocation RCC." Approximately 50 renal cell carcinomas with gene fusions involving the anaplastic lymphoma kinase (ALK) gene have now been reported. While those with a Vinculin-ALK fusion have distinctive features (predilection to affect children with sickle cell trait and to show solid architecture with striking cytoplasmic vacuolization), other ALK-fusion RCCs have more varied clinical presentations and pathologic features. This review summarizes our current knowledge of these recently described RCC.