Search

Cellular fibromas represent ~10% of ovarian fibromas. Mitotically active cellular fibromas show mild nuclear atypia but ≥4 mitoses/10 high-power fields: the clinical course is usually uneventful but literature review is lacking. A 34-yr-old woman underwent left oophorectomy for a 9-cm ovarian mitotically active cellular fibroma at another hospital. The tumor was cellular (spindle cells in fascicular and storiform patterns) revealing mild atypia and 4 nonatypical mitoses/10 high-power fields without necrotic areas. After 16 yr, the tumor recurred as a 5-cm peritoneal nodule on the anterior sigmoid wall near the sigmoid-rectal junction. Frozen section revealed a spindle cell tumor invading the intestinal tunica muscularis propria: a gastrointestinal stromal tumor was favored as previous history was unavailable at that time. Intestinal resection was performed: no residual tumor was found. The patient was followed-up for 8 yr without further recurrences. The peritoneal nodule showed 2 mitoses/10 high-power fields and pericellular reticulin staining. The tumor was variably positive for vimentin/bcl-2/melan-A/CD56/ER/PR/α-inhibin/CD10/calretinin, focally positive for desmin, negative for pan-cytokeratin/actin/EMA/CD34/HMB45/CD117/CD99/S100/synaptophysin. The Ki67-index was ~9%. To our systematic literature review, 7 additional recurrent cases were reported. We describe a mitotically active cellular fibroma recurring after the longest interval of time. Extensive sampling of difficult cases should exclude malignant areas. Moderate nuclear atypia, tumor rupture, adhesions to pelvic/abdominal organs, infarction with extraovarian involvement, and incomplete excision may lead to relapse but there are conflicting data: prolonged follow-up can be suggested in these cases.

Background: It has been known that the “atypia of undetermined significance (AUS)/follicular lesion of undetermined significance (FLUS)” category is the most problematic category in Bethesda system due to its highly heterogeneous morphological features. Recently, it has been reported that aspirates including nuclear atypia in the AUS/FLUS category have a higher risk of malignancy. Aims: This study aimed to assess each nuclear property in aspirates with cytological atypia and also to determine the relationship with the risk of malignancy. Material and Methods: We reviewed 980 AUS/FLUS fine-needle aspirations (FNAs) performed between '2012 and 2019' at a single institution. We classified these aspirates into four groups: AUS-N (nuclear atypia), AUS-A (architectural atypia), AUS-H (Hurthle cell change), and AUS-O (other). Nuclear features were detailed sub-classified; size and shape (enlargement, elongation, and overlapping), membrane irregularities (irregular contours, grooves, pseudoinclusion), and chromatin characteristics (pale chromatin). The estimated risk of malignancy (ROM) was calculated for each subgroup. Results: Of 980 AUS/FLUS cases, follow-up histological outcome data were available for 209 cases. Among these cases, the estimated ROM was 27.8%. The ROM were 26.4%, 15.4%, and 22.5% for AUS-N, A, and H, respectively. The most common nuclear findings associated with ROM were nuclear groove (67.9%); irregular contours (76.9%) suspected pseudoinclusion (100%) and overlapping (56%) (P < 0,001). But nuclear findings such as nuclear enlargement, mild pleomorphism, or pale chromatin have a similar ROM as architectural atypia. Conclusion: Although it is known that the presence of cytological atypia in an AUS/FLUS nodule increases the estimated risk of malignancy, all nuclear properties are not equally effective in predicting malignancy risk. Emphasizing nuclear atypia details in reports of AUS case may be a more sensitive way to identify nodules with a high risk of malignancy.

Endometriosis is a relatively common condition in which endometrial tissue is established in locations outside the uterus where, like the eutopic endometrium, it responds to hormonal stimuli and develops internal bleeding, inflammation, and fibrosis. These changes are associated with chronic and often debilitating cyclic pain and infertility. The pathogenesis of endometriosis is multifactorial, and several theories have been proposed to explain it. These include retrograde menstruation, celomic metaplasia, embryologic rests, and lymphovascular spread. Hormones, immunologic status, and genetic factors may also play a role. In most patients, the disease involves pelvic organs, but rarely it may also extend to a large variety of distant locations in the body. Patients with ovarian endometriosis are at higher risk for developing ovarian carcinomas including endometrioid and clear cell carcinomas. Some of these carcinomas may arise in a background of structural and/or nuclear atypia within the endometriotic foci. There is no known cure for endometriosis and treatment mostly consists of managing chronic pain or infertility.

Embryonal rhabdomyosarcoma of the uterine cervix is a rare neoplasm which is almost invariably associated with pathogenic somatic or germline DICER1 mutations; patients with germline mutations have DICER1 syndrome. We report 2 subtle cervical embryonal rhabdomyosarcoma, one occurring in a 21-yr-old woman with a known history of DICER1 syndrome and the other in a 19-yr-old woman with no history of DICER1 syndrome or DICER1-associated neoplasms. Both neoplasms focally involved otherwise benign endocervical polyps and were characterized histologically by subtle areas of increased stromal cellularity, nuclear atypia and mitotic activity; there was focal nuclear staining of these areas with the skeletal muscle markers myogenin and myoD1. In both cases, demonstration of a somatic DICER1 RNase IIIb mutation in the tumor was instrumental in establishing the diagnosis. We believe these neoplasms represent the earliest discernible phase of cervical embryonal rhabdomyosarcoma. Pathologists should have a high index of suspicion when atypical stromal elements are present in endocervical polyps and immunohistochemistry together with DICER1 sequencing will assist in diagnosis.

The Bethesda System for Reporting Thyroid Cytopathology has paved the way for comparisons of the practice of thyroid cytology in many different regions. However, there have been comparatively few studies documenting differences between Asian and non-Asian practice. Here, we aim to compare a few key parameters between the two regions, focusing on the indeterminate category of atypia of undetermined significance (AUS)/follicular lesion of undetermined significance (FLUS). We compared its incidence, resection rates (RRs), risk of malignancy (ROM), rate of repeat fine needle aspiration (rFNA), ROMs of cytomorphologic subcategories of nuclear atypia (AUS-N) vs. architectural atypia (AUS-A), and, finally, the incidence of papillary thyroid carcinoma (PTC) vs. follicular neoplasms (FNs) in resected AUS/FLUS cases in Asian and non-Asian regions. Where possible, these metrics were compared with the Singapore experience from a tertiary referral institution. While the incidence of AUS/FLUS was similar in both regions, we found geographical differences in the RRs and ROMs, which may reflect a higher collective threshold for surgery in Asian countries. However, both cohorts showed higher ROMs in the AUS-N subcategory as compared to the AUS-A subcategory, supporting the subclassification of the AUS/FLUS based on the presence of nuclear atypia. We also observed a higher incidence of AUS-N coupled with a higher incidence of PTC in resected AUS/FLUS nodules in Asian cohorts, while AUS-A and follicular-patterned neoplasms featured more prominently in the non-Asian cohorts. These incidences may account for the starkly different molecular approaches that we noted-in Asian (chiefly Korean and Chinese) centers, BRAF mutational analysis was favored, while gene panels and gene expression classifiers were more frequently applied in non-Asian centers (chiefly in the United States of America). Overall, the data from Singapore appears more closely aligned to non-Asian trends, despite its geographical location in Southeast Asia and its predominantly Asian population. We conclude that there is significant heterogeneity in the outcomes of the AUS/FLUS categories between and within regions, which is only partially explained by regional variations, and may also reflect different regional diagnostic and management practices. This highlights the importance of understanding the local context in the interpretation of indeterminate Bethesda categories, rather than adopting a "one-size fits all" approach.

The objective of this study is to investigate the signal changes and optimal scanning concentration of MRI in tumor tissues of tumor-bearing nude mice by SPIO-shRNA molecular probes. 30 BALB/c tumor-bearing nude mice were randomly divided into 5 groups with 6 mice in each group. At the given scanning time (before and 27 h after injection), the caudal vein was respectively injected with iron content of 6 mg·kg−1, 12 mg·kg−1, 18 mg·kg−1, 24 mg·kg−1, and 30 mg·kg−1, and MR examination was simultaneously performed to measure signal intensity changes of tumor tissue and contralateral muscle tissue in each concentration group. After each examination above, the nude mice were sacrificed immediately, and the tumor and muscle tissues were removed for HE and Prussian blue staining,and observed under light microscope. Nude mice in 6 mg, 12 mg and 18 mg groups all survived after probe injection, but some nude mice died in 24 mg and 30 mg groups after probe injection or during scanning. The signal changes of T2WI and T2*WI sequences were the most obvious in MR scanning sequences. Compared with other groups, the signal intensity of the tumor tissue in 18 mg, 24 mg and 30 mg groups were most obvious (P 0.05 ); HE staining indicated that structural disorder of tumor tissue as well as increase of nuclear atypia. Prussian Blue staining showed that blue-stained iron particles were present in each experimental group,and the most densely distributed were in 18 mg,24 mg and 30 mg groups. Tumor tissue could be well labeled with SPIO-shRNA molecular probes, and the optimal MR scanning concentration (iron content) is 18 mg·kg−1.

Aims: To investigate the morphological and molecular characteristics of Leydig cell tumours (LCTs) of the testis for the identification of cases that may metastasise. Methods and results: Six parameters for a predictive model of the metastatic risk were evaluated in 37 benign and 14 malignant LCTs of the testis [LCT Scaled Score (LeSS)]. The tumour size (benign LCTs, mean 13.3mm; malignant LCTs, mean 44mm) (P&nbsp

We demonstrated the clinicopathological findings of 13 myoepitheliomas of soft tissue and bone (MESTBs) and two myoepithelioma-like tumors of the vulvar region (MELTVRs), focusing on the association between nuclear atypia and clinical course, and the utility of immunohistochemistry (IHC) of pleomorphic adenoma gene 1 (PLAG1) for the pathological diagnosis of these tumors. Of the 13 MESTBs, eight, one and four cases exhibited mild, moderate and severe nuclear atypia, respectively. Two cases with venous invasion showed severe nuclear atypia and both died of advanced disease. Two MELTVR cases showed moderate nuclear atypia and had no evidence of disease after surgery. On IHC, 12 of 13 (92.3%) MESTBs showed PLAG1 immunoreactivity and none of the MELTVRs expressed PLAG1. In addition, MELTVRs showed loss of INI1 expression. In contrast, all MESTBs retained INI1 expression. Fluorescence in situ hybridization detected EWSR1, FUS and PLAG1 rearrangement in 5 (38.5%), 0 (0%) and 2 (15.4%) of the 13 MESTBs, respectively. No EWSR1, FUS and PLAG1 rearrangement were observed in the METLVRs. In conclusion, MESTBs with both severe nuclear atypia and venous invasion would be indicative of malignant potential. PLAG1 might be a useful IHC marker in MESTB diagnosis.

Longitudinal melanonychia in paediatric patients often represents a difficult diagnostic challenge, and studies emphasising its clinical and histopathological features are limited due to its low incidence in childhood.We retrospectively analysed 35 paediatric cases identified by excision specimens on their clinicopathological features, and performed fluorescence in-situ hybridisation on 13 available cases. Fingernails (77.1%) were more likely to be affected. Total melanonychia and Hutchinson's sign were observed in 10 (28.6%) and 14 (40.0%) cases, respectively. Nail dystrophy at diagnosis was present in five cases. After complete excision of the lesions, four patients relapsed during follow-up (mean = 38 months). Seventeen cases were diagnosed as lentigines and 18 as naevi, among which 11 cases were categorised as lentigines/naevi with atypical melanocytic hyperplasia. Mild-to-moderate nuclear atypia, confluency of melanocytes, focal pagetoid spread and peri-ungual skin involvement were found in 25.7% (9 of 35), 40.0% (14 of 35), 40.0% (14 of 35) and 40.0% (14 of 35) of cases, respectively. Thirteen cases tested by fluorescence in-situ hybridisation showed no copy number aberration at the probed loci. There was a statistically significant difference in the following features between patients aged less and more than 10 years (P 0.05): cytomorphology, mild-to-moderate nuclear atypia, confluency of melanocytes, focal pagetoid spread and melanocyte count.Some concerning clinicopathological characteristics, which are signs indicative of melanoma in adults, are not uncommon in paediatric longitudinal melanonychia, especially in patients aged ≤ 10 years. Owing to the extremely low incidence of melanoma in paediatric longitudinal melanonychia, in most circumstances a more conservative clinical management strategy should be adopted.

Highlights • Colon MiNEN, in this case, adenocarcinoma and NET G1 is a rare tumor. • Preoperative diagnosis of MiNEN is difficult, and detailed observation of histopathology is important. • Prognosis depends on the more aggressive components of adenocarcinoma or NET., Introduction Neuroendocrine tumor (NET) that develops in the right-sided colon is relatively rare. Coexistence of adenocarcinoma and NET is extremely rare, and such cases are called mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN). Presentation of case Colonoscopy in an 85-year-old woman for an anemia examination indicated laterally spreading tumor-nongranular (LST-NG) in the transverse colon. Colonoscopy and endoscopic ultrasonography (EUS) showed that the depth of the tumor invasion was deep submucosal. The tumor localization was diagnosed as transverse colon close to the hepatic curvature by enema. Computed tomography (CT) showed no obvious lymph node or distant metastasis. Based on these findings, laparoscopic transverse colectomy with D2 lymphadenectomy was performed. Pathologically, most of the tumor was well-differentiated tubular adenocarcinoma, but some solid follicles of polygonal tumor cells with poor nuclear atypia were observed. Immunostaining was positive for synaptophysin and diagnosed as NET G1. This tumor consisted of adenocarcinoma and neuroendocrine tumor, so we diagnosed it as MiNEN and classified the tumor as fT1N0M0 fStage I (TNM Classification of Malignant Tumors, 8th Edition). Since it was an early stage cancer, postoperative adjuvant therapy was not performed. No recurrence has yet been noted. Discussion Although MiNEN is extremely rare, the detailed pathological specimen observation and diagnosis are important because long-term follow-up after surgery is needed, as is the adequate selection of postoperative adjuvant therapy. Conclusion It is important to elucidate the mechanisms involved in the coexistence of NET and adenocarcinoma and to apply these findings to future medical care.

Giant cell tumor of bone is a locally aggressive, rarely metastasizing neoplasm. Evidence suggests that the neoplastic cells may be osteoblastic in differentiation. Standard treatment is surgical removal, but medical therapy with denosumab, an inhibitor of receptor activator of nuclear factor-κβ ligand, has become a component of patient management in select cases. Denosumab-treated giant cell tumor of bone (DT-GCTB) shows drastic morphologic changes including the presence of abundant bone. To further determine the relationship of the neoplastic cells to osteoblast phenotype, we performed a morphologic and immunohistochemical study on a series of DT-GCTB. Cases of DT-GCTB were retrieved from surgical pathology files, available slides were reviewed, and immunohistochemistry for H3.3 G34W, SATB2, and p63 was performed. The cohort included 31 tumors from 30 patients (2:3 male:female), ages 15 to 73 years (median=36 y). The morphology of post-denosumab-treated tumors ranged from tumors composed of an abundant bone matrix with few spindle cells to spindle cell-predominant tumors. Five had focal residual classic CGTB, and 2 manifested mild nuclear atypia. The majority expressed all markers: 86.2% for H3.3 G34W, 96.7% for SATB2, and 100% for p63. All markers stained the various tumor components including spindle cells and the cells on the surface of and within the treated tumor bone matrix. Most markers were also positive in reactive-appearing woven bone adjacent to tumor: 84.6% for H3.3 G34W, 100% for SATB2, and 68% for p63. These findings suggest that denosumab treatment of giant cell tumor of bone results in osteoblastic differentiation with bone production.

Pure intravascular growth of epithelioid hemangioma (EH) is exceptional. Herein, we report a series of 21 intravascular EHs, representing a potential serious diagnostic pitfall by mimicking malignant vascular neoplsms with epithelioid morphology. The tumors developed in 12 males and 4 females, aged from 11 to 71 years (mean age 40.2 years) with a predilection for the extremities (13 of 21, 61.9%), followed by the head and neck (8 of 21, 38.1%). Lesions ranged in size from 2 to 30 mm (mean size 13 mm). The most common presenting feature was a slowly growing nodule. Most neoplasms were solitary (13 of 16 patients, 81.2%) but three patients developed more than one intravascular EH (3 of 16, 18.8%). Treatment consisted of complete surgical excision and was generally curative. Follow-up was available for 13 lesions that had developed in ten patients (range 4-72 months, mean 27.3 months). No recurrences or development of additional tumors were observed. All 21 lesions developed in subcutaneous veins. Two morphological patterns of intravascular epithelioid endothelial cell proliferation were observed: (1) a lobular capillary hemangioma-like proliferation with variable formation of open vascular lumina and (2) a solid proliferation generally lacking open vascular spaces. A lobular capillary hemangioma-like pattern was the sole pattern in nine lesions, a mixed lobular hemangioma-like pattern, and solid pattern in eight and a pure solid pattern in four intravascular EHs. Mitotic activity in epithelioid endothelial cells ranged from 0 to 7 mitoses per 10 high-power field (mean 2.1 mitoses per 10 HPFs). Six lesions displayed brisk mitotic activity of five or more mitoses per 10 HPF (6 of 21, 28.5%). The number of mitoses was usually more prominent in areas with solid growth. Atypical mitoses were not observed. No intratumoral necroses were seen. Cytological atypia was mild (20 out of 21 cases). By immunohistochemistry, all tumors were positive for CD31 (14 out of 14) and ERG (5 out of 5). While all tested cases were FOS negative by immunohistochemistry (6 out of 6), one out of six cases (case 6) displayed FOSB nuclear positivity in about 30% of the lesional endothelial cells. Eight cases were analysed by FISH for the presence of FOS and FOSB gene rearrangements. While all cases were negative for FOSB rearrangements, a single case proved positive for FOS gene break-apart. In conclusion, intravascular growth of EH is not associated with adverse biological behavior. Solid intravascular proliferations of endothelial cells can mimic a malignant vascular tumor with epithelioid morphology. Nevertheless, intravascular EHs display mild cytological atypia coupled with low mitotic activity, and a lack of atypical mitoses, pronounced nuclear atypia, multilayering or tumor necrosis. Finally, the FOS gene is infrequently rearranged, and there are no FOSB gene abnormalities in this subset of EHs, suggesting a potential distinct pathogenesis than most classic EHs.

Benign thyroid lesions such as multinodular goiter and adenomatoid nodules are well-circumscribed lesions displaying a macrofollicular growth pattern and lack of nuclear atypia. The highly unusual macrofollicular variant of follicular thyroid carcinoma (MV-FTC) mirrors these attributes and is thereby misclassified by cytological examination of fine-needle aspiration biopsies. The MV-FTC diagnosis is instead suggested following histological investigation, in which malignant attributes, most commonly capsular invasion, are noted. The bulk of MV-FTCs described in the literature arise in younger female patients and carry an excellent prognosis. A recent coupling to mutations in the DICER1 tumor suppressor gene has been proposed, possibly indicating aberrancies in micro-RNA (miRNA) patterns as responsible of the tumorigenic process. We describe the cytological, histological and molecular phenotype of a 35 mm large MV-FTC arising in the right thyroid lobe of a 33-year-old female with a family history of multinodular goiter. The tumor was encapsulated and strikingly inconspicuous in terms of cellularity and atypia, but nevertheless displayed multiple foci with capsular invasion. A next-generation molecular screening of tumor DNA revealed missense variants in DICER1 (p. D1709N) and MET (p. T1010I), but no established fusion gene events. After sequencing of germline DNA, the DICER1 mutation was confirmed as somatic, while the MET variant was constitutional. The patient is alive and well, currently awaiting radioiodine treatment. This MV-FTC mirrors previous publications, suggesting that these tumors carry a favorable prognosis and predominantly arise in younger females. Moreover, DICER1 mutations should be considered a common driver event in the development of MV-FTCs.

Intracranial anaplastic hemangiopericytoma (AHPC) is a rare and malignant subset of solitary fibrous tumor/hemangiopericytoma (SFT/HPC) as per the WHO 2016 Classification of Tumors of the Central Nervous System. AHPC portends a poor prognosis and is associated with higher rates of recurrence/metastasis in comparison with SFT/HPC. Accordingly, it is critical to continue to define the clinical course of patients with AHPC and in so doing further refine clinicopathologic/immunohistochemical (IHC) criteria needed for definitive diagnosis. Herein, we describe clinical/histological characteristics of six patients with AHPC. In addition, we reviewed and analyzed the expression of various IHC markers reported within the literature (i.e., a total of 354 intracranial SFT/HPCs and 460 meningiomas). Histologically, tumors from our six patients were characterized by a staghorn-like vascular pattern, mitotic cells, and strong nuclear atypia. Immunohistochemically, all tumors displayed positive nuclear staining for STAT6; other markers, including CD34 and Bcl-2, were expressed only in three patients. Analysis of IHC expression patterns for SFT/HPC and meningioma within the literature revealed that nuclear expression of STAT6 had the highest specificity (100%) for SFT/HPC, followed by ALDH1 (97.2%) and CD34 (93.6%). Of note, SSTR2A (95.2%) and EMA (85%) displayed a high specificity for meningioma. Anaplastic SFT/HPC is a tumor with poor prognosis that is associated with higher rates of recurrence and metastasis in comparison with SFT/HPC. Given that anaplastic SFT/HPC requires more aggressive treatment than meningioma despite of a similar presentation on imaging, it is crucial to be able to distinguish between these tumors.

Introduction This case-series is aimed to describe the natural history of epithelioid sarcoma (ES) and to provide insights into the differential clinical behaviour of its two variants (“classic-type” and “proximal-type”). The value of a subtype-adapted grading system based on pathological features is explored. Methods Data from consecutive, primary, localised, INI1-deleted ES operated at three Italian sarcoma reference centres (1995–2015) were included. Centralised pathological review was performed. Classic-type ES was broken down into “high-grade” and “low-grade”, according to number of mitoses, evidence of necrosis and nuclear atypia. Five- and 10-year overall survival (OS) and crude cumulative incidence (CCI) of local recurrence (LR) and distant metastasis (DM) were estimated. Results Fifty-two patients were included. 5- and 10-year OS estimates were 70% and 47% in the whole series, 57% and 37% in patients with proximal-type ES, 77% and 54% in patients with classic-type ES (P = 0.02). In classic-type ES, 5- and 10-year OS was higher for low-grade (95% and 72%, respectively) than high-grade tumours (P = 0.002). 5- and 10-year CCI estimates for LR were 21% and 33% in the whole series. 5- and 10-year CCI estimates for DM were 35% and 39% in the whole series, both 28% in classic-type ES, 47% and 59% in proximal-type ES (P = 0.03). Conclusions Suffering from a proximal- or a classic-type is the stronger predictor of outcome in patients with localised ES, with proximal-type ES patients having lower survival due to a higher tendency toward metastatic spreading. However, the “high-grade” classic-type ES was associated with outcomes close to proximal-type ES.

A challenge in the diagnosis of prostate pathology is the numerous benign mimics of prostatic adenocarcinoma. Most of these lesions have no clinical significance but may be misinterpreted as cancer in biopsy specimens. In this review we describe the features of some of the more common benign mimics and discuss how they can be distinguished from carcinoma. The diagnostic entities most commonly associated with a false positive diagnosis of cancer are the atrophic group of lesions that include simple atrophy, partial atrophy and post-atrophic hyperplasia. Benign proliferations exhibit architectural atypia, often with closely packed small glands, but with no or little nuclear atypia. The most common diagnostic pitfall of this group is adenosis, which may have an even more atypical architecture than some cancers. A common denominator of atrophy and benign proliferations is that they consist of small glands that may have a patchy or absent basal cell layer, which adds to the diagnostic difficulties. Amongst hyperplastic and metaplastic lesions, basal cell hyperplasia may be misinterpreted as cancer because of its dark basophilic glands that sometimes display a certain degree of nuclear atypia and occasionally exhibit a pseudoinfiltrative pattern. The most important extraprostatic anatomical structure causing diagnostic difficulties is the seminal vesicle. The closely clustered small glands and often strikingly atypical nuclei of seminal vesicle epithelium may be misinterpreted as cancer. Awareness of these mimics is of paramount importance for the practicing pathologist as a false positive diagnosis of prostate cancer may lead to unnecessary radical therapy.

Spindle cell lipoma is a rare variety of lipoma that usually appears in subcutaneous tissue, for example, the posterior neck, shoulders, and back region, in middle-aged and older males. We reported a rare case of spindle cell lipoma of the floor of mouth. A 68-year-old man had a painless swelling of the floor of mouth. Clinical and image examination revealed that the mass was encapsulated, well-circumscribed, smooth-surfaced, and soft. Inside of the lesion was the same signal as adipose tissue, and the mass showed high signals at T1 and T2 weighted sequence in magnetic resonance imaging. However, the internal properties were non-uniform, and the vascular pattern was observed. Therefore, biopsy was performed before removal operation, and the mass was diagnosed as no malignancy. The encapsulated yellow mass was removed under general anesthesia. The histopathology showed that the well-demarcated mass was composed of mature adipocytes and spindle cells with bundles of collagen fibers. The size of mature adipocytes was uniform, and nuclear atypia was not observed. In immunohistochemical staining, the adipocytes were positive to S-100, and the spindle cells showed positive for CD34 and bcl-2 but S-100 negative. Based on the pathological features, the diagnosis was spindle cell lipoma. Differentiation of spindle cell lipoma includes solitary fibrous tumors, neurofibromas, subcutaneous fibrous malignancies, and well differentiated lipomas. S-100, CD34, and bcl-2 was able to differentiate these tumors and was very useful for the diagnosis of spindle cell lipoma. There were no signs of recurrence after 1-year follow up since the operation.

Mucinous cystic neoplasms of the liver involving the extrahepatic biliary tract is a rare slow-growing benign neoplasm of biliary system that has an early clinical presentation with obstructive jaundice. These tumors have a high risk of malignant transformation, which is difficult to diagnose preoperatively by radiology or endoscopy. We present a 31-year-old female patient who presented with complaints of pain abdomen, vomiting, fever, and obstructive jaundice. Ultrasound abdomen showed features suggestive of cholangitic abscess. Computed tomography abdomen showed features suggestive of cholangitic abscess and abrupt termination of the proximal CBD secondary to the stricture. A left hemi-hepatectomy was performed which showed a multiloculated cystic liver lesion with the involvement of extrahepatic duct, cystic duct, and proximal common bile duct. Histopathology showed cyst was lined by mucin secreting columnar epithelium without nuclear atypia, the wall the cysts showed ovarian-like stroma, and the diagnosis of mucinous cystic neoplasms of the liver and extrahepatic biliary tract with ascending cholangitis was made. Regular follow-up by clinical and radiological examination at 6 months did not reveal any recurrence.

Background Spinal schwannomas are benign nerve sheath neoplasms that constitute about 30% of extramedullary spinal cord tumors. They are usually small, well-encapsulated tumors with low mitotic activity and concurrently carry a low risk of recurrence. Here, we report a case of atypical histologic variant of spinal schwannoma that had higher cellular density, nuclear atypia, and lack of encapsulation. To our best knowledge, no such cases of this atypical variant with regards to lumbar spine have been reported in the literature. Case Description A 66-year-old male had an incidental left-sided paraspinal mass discovered while undergoing workup for cholecystitis. On examination, the patient was neurologically intact. Imaging revealed the presence of a contrast-enhanced, partially cystic mass arising from the L3-4 intervertebral foramen and causing left psoas muscle displacement. A minimally invasive left L3-4 posterior extracavitary resection was done. Histopathologic examination revealed a partly unencapsulated tumor with higher than usual cellular density and nuclear atypia, resulting in a diagnosis of “atypical schwannoma.” Imaging at 6 months' follow-up showed stable postsurgical changes and residual tumor with no evidence of progression/recurrence. Conclusions Atypical schwannoma has higher cellular density and nuclear atypia and lacks encapsulation. A review of the literature suggests an increased risk of recurrence when compared with typical variants, and complete tumor removal should be attempted.

Aims Ectomesenchymal chondromyxoid tumour (ECT) is a rare benign intraoral tumour which almost exclusively presents as a small mass of the anterior dorsal tongue. Recently, the RREB1-MRTFB (previously known as MKL2) fusion gene has been identified in 90% of ECTs, all located in the tongue, emphasising its genetic distinctiveness. Here, we report two mesenchymal tumours involving the superior mediastinum of adult women with RREB1-MRTFB fusions. Methods and results Both tumours presented as well-circumscribed paravertebral masses that were clinically suspected to be schwannoma. After fragmented resection, recurrence was not observed at 27 and 18 months. Although tumours were originally unclassifiable, next-generation sequencing detected identical RREB1 (exon 8)-MRTFB (exon 11) fusion transcripts, which were validated by reverse transcriptase-polymerase chain reaction, Sanger sequencing, and fluorescence in-situ hybridisation. Both tumours shared hyalinised areas with round cells embedded in a cord or reticular manner. The tumour cells showed mild nuclear atypia of possible degenerative type with very low mitotic activity, and were at least focally positive for S100, glial fibrillary acidic protein, smooth muscle actin and epithelial membrane antigen. Overall, these findings suggest that they may represent previously undescribed extra-glossal ECT involving the mediastinum. However, the histology was not classic for ECT, because that in case 2 was predominated by storiform growth of spindle cells, whereas the tumour in case 1 lacked myxoid change. Conclusions We have provided the first evidence that RREB1-MRTFB fusion is not limited to tumours in the head region, and whether such tumours represent extra-glossal ECTs requires further research.

"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

Objective Borderline ovarian tumours (BOTs) are characterized by the presence of cellular proliferation and nuclear atypia without stromal invasion. Compared to malignant ovarian tumours, BOTs have better prognoses. The most important treatment of BOT is surgery. Considering the good prognosis of BOT, fertility-sparing surgery (FSS) can be considered for young women who desire to preserve fertility. Our study evaluated the pregnancy rate in patients with childbearing desire, the efficacy and risk of recurrence of women affected by BOTs who have undergone FSS. Materials and methods Patients characteristics have been restrospectively retrieved for diagnosis made from June 2000 to December 2017 from San Raffaele Hospital and Policlinico Cagliari. Patients underwent FSS for BOT were interviewed about child wishing and pregnancy outcomes. Results 85 patients were recruited for the study. Median age at diagnosis was 33 years. Unilateral salpingo-oophorectomy was performed in 33 patients (38%), unilateral cystectomy in 40 (47%) and 12 underwent both procedures (14%). 40 women (50%) tried to conceive after surgery. The pregnancy rate was 73% and live birth rate was 67%. Childbearing desire and age at diagnosis were significantly associated with the pregnancy rate. Conclusions Conservative surgical treatment seems to be a reasonable therapeutic option for women with BOTs who wish to preserve fertility. Our results suggest that the obstetric outcomes after FSS are promising. Maternal desire and the age of diagnosis are the most important factors affecting PR after surgery. Fertility counselling should be an integral part of the clinical management of women with BOT.

Objective The aim of the study was to study the clinicopathological and immunohistochemical features of gastrointestinal stromal tumours and correlation with KIT/PDGFRA mutations. Material and method Eighty consecutive resected cases were genotyped for KIT exons 11, 9, 13, 17 and PDGFRA exons 18, 14, 12 and correlated with histomorphology by nonparametric tests. Results Forty-seven cases (58.8%) were in the high-risk group. Males had higher rates of KIT exon 11 and PDGFRA exon 18 mutations than females (p=0.03). KIT and PDGFRA mutation frequencies were lower (58.8%) than western data showing KIT exon 11 mutation in 63.8%, KIT exon 9 mutation in 19% and PDGFRA exon 18 mutation in 17% of the cases. Extragastrointestinal stromal tumours (n=6) showed 100% mutation. KIT exon 11 deletion was associated with gastric location (60%) (p=0.04), spindle cells (63.3%), and high-risk stratification (66.6%) (p=0.01) while KIT exon 9 mutation was common in small intestine (66.7%) (p=0.04), in higher risk groups (66.7%) (p=0.01) and 75% of codon 502-503 duplications (p=0.03). PDGFRA 18 mutation was common in males (p=0.03), in gastric location (62.5%) (p=0.04), in cases showing mild to moderate atypia (62.5%) (p=0.01) and lower risk stratification (62.5%) (p=0.01). KIT/PDGFRA mutations were significantly associated with gender (p=0.03), location (p=0.04), nuclear atypia (p=0.01) and risk stratification (p=0.01). Conclusion Morphological features and anatomic location may be useful in deciding molecular testing strategy, particularly in resource-limited settings, when a plethora of targetable mutations are present. An algorithm may be derived for genotyping with KIT exon 11 and PDGFRA exon 18 heading the list of targetable mutations. This approach may reduce financial burden on patients as well as workload on hospital staff.

Background Lobular endocervical glandular hyperplasia (LEGH) is a disease considered to be the origin of tumorigenesis of minimal deviation adenocarcinoma, which has characteristic expression in the gastric pyloric mucosa. It is difficult to diagnose by nuclear findings because of lower nuclear atypia. In this study, nuclei of endocervical (EC) and LEGH cells were digitized, and nuclear information was quantified from nuclear images and objectively evaluated using a computer. We examined whether it is possible to distinguish between EC and LEGH cells, which is difficult by human eyes. Methods Signal intensity, morphological features, Otsu thresholding technique and gray-level co-occurrence matrix (GLCM) features were calculated from nuclei of EC and LEGH cells on cytology microscopic images. Then, discriminant analysis was performed using the significant difference test and linear support vector machine (LSVM). Results GLCM features in LEGH cells were higher than those in EC cells. The nuclei of LEGH cells had a higher frequency of signal value pairs with a larger signal value difference than that of EC cells. Therefore, LEGH cell nuclei are thought to have more chromatin granules, and the chromatin is coarse and granular. Moreover, in the LSVM discriminant analysis, the accuracy of GLCM calculated using these features was 85.4%. Conclusion In this study, GLCM accurately demonstrated the nuclear chromatin distribution and coarseness. Discriminant analysis of EC and LEGH cells using GLCM features is useful.

Background Salivary duct carcinoma (SDC) is an uncommon and highly aggressive primary salivary gland neoplasm. Cytomorphologic features of SDC include cellular smears, nuclear atypia, prominent nucleoli, cribriform and papillary architecture, and background necrosis. The presence of oncocytic features has been described but not adequately characterized in the current literature. Method This study cohort consisted of 14 cases of histologically proven SDC with previous salivary gland fine needle aspiration (FNA). The cytologic material of each case was semi-quantitatively analyzed and evaluated for various cytomorphologic, architectural, and background features. Results Twelve SDCs were located in the parotid gland and two in the submandibular gland. In two cases the initial cytologic diagnoses was Warthin tumor or favor Warthin tumor. Moderate to marked degree of oncocytic changes were noted in all cases except one case. Nuclear atypia was variable with most cases exhibiting moderate to high-grade nuclear features, while four cases demonstrated low-grade nuclear cytomorphology. Cytoplasmic vacuolation was seen in nine cases and variable amount of background necrosis was observed in eight cases. Cribriform and papillary architecture was recognized in only six cases. Background lymphocytes were absent in all but one case. Conclusions Precise diagnosis of SDC based on cytomorphologic features alone can be challenging. Oncocytic change is one of the most consistent features observed in this case series and when associated with less pronounced cytologic atypia, can potentially lead to misdiagnosis as Warthin tumor. SDC should be considered in the differential diagnosis of oncocytic salivary gland neoplasms where precise diagnosis is not possible.

Background In the current version of The Bethesda System (TBS) for thyroid cytopathology, the atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) category has an estimated risk of malignancy of 10% to 30%. Diagnostic criteria include presence of nuclear atypia, suggestive of papillary thyroid carcinoma (PTC), as well as other types of atypia, which can be seen with non-malignant entities. Aim of this study was to investigate differential outcomes of AUS/FLUS, based on specific morphologic criteria, and assess their respective malignancy risks. Methods From a total of 1233 patients undergoing thyroid FNAs between 2010 and 2014 at the University of Washington, 119 had AUS/FLUS without nuclear atypia, and 64 with nuclear atypia. Outcomes for patients with and without nuclear atypia (with the exception of 24 patients lost to follow-up) were evaluated and results were compared. Results 16/57 (28.1%) patients with AUS/FLUS and nuclear atypia subsequently had carcinomas on thyroidectomy, statistically higher than the 8/102 patients (7.8%, P = .001) without nuclear atypia. When comparing only patients who underwent surgery (n = 63), again those with AUS/FLUS and nuclear atypia had statistically higher rates of carcinoma (16/31, 51.6%), compared to those without (8/32, 25%; P = .0394). Overall, 24/159 (15.1%) of patients with AUS/FLUS had carcinoma on subsequent histology. Conclusion Malignancy rates for AUS/FLUS were in line with TBS estimated risks. However, our data demonstrate that the presence or absence of nuclear atypia is associated with different malignancy rates, suggesting the possibility that the AUS/FLUS category may best be split into two subcategories with different implied risks of malignancy.

We described a case of low-grade fibromatosis-like spindle cell carcinoma (FLSCC) of the breast of a 49-year-old woman, which was diagnosed by excisional biopsy. The histopathology was characterized by bland neoplastic spindle cells with mild or no nuclear atypia, mimicking a benign mesenchymal tumor. An immunopanel of markers including pancytokeratin, p63, smooth muscle actin (SMA), CD10, and β-catenin was performed to establish the diagnosis and exclude other mimickers. The patient subsequently received modified radical mastectomy and was alive without disease for 10-year follow-up. Low-grade fibromatosis-like spindle cell carcinoma is a rare subtype of metaplastic carcinomas of the breast and typically occurs as palpable breast mass in an older woman. It can be histologically confused with nodular fasciits, desmoids-type fibromatosis, and inflammatory myofibroblastic tumor. Immunohistochemical study was essential for a correct diagnosis. It behaves as a locally aggressive disease but with a low potential of regional lymph node or distant metastasis.

Female adnexal tumors of probable Wolffian origin are rare and present a diagnostic challenge due to their morphological and immunohistochemical overlap with more common ovarian and broad ligament entities. We evaluated the morphological, immunohistochemical, and molecular features of 15 tumors of probable Wolffian origin. Patients ranged from 32 to 69 (mean 47) years and tumors from 1.8 to 30 (mean 10) cm. All except one arose in para-adnexal soft tissues. Follow-up was available for six patients, five of whom were alive and well, while the sixth, who had extra-adnexal disease at diagnosis, died from unrelated causes. The following patterns were noted: tubular (all tumors), solid 11/15 (73%), sieve-like 7/15 (47%), and reticular 1/15 (7%). A myxoid background was present in 3/15 (20%) of tumors and eosinophilic luminal secretions in 11/15 (73%). Most tumors (12/15, 80%) had low-grade nuclear atypia, while three showed foci with scattered high-grade atypia. Mitotic index ranged from 0 to 17 (mean 4) per ten high-power fields. Tumors were positive for pankeratin and negative for TTF-1. EMA, GATA3, and PAX8 were positive in 2/10 (20%; focal), 3/15 (20%; focal), and 1/15 (7%; focal) of tumors, respectively. CD10, SF-1, calretinin, inhibin, ER, PR, cytokeratin 7, and WT1 were variably expressed. Pathogenic mutations were rare and included STK11 (n = 3), APC (n = 1), and MBD4 (n = 1). Copy number variations were detected in the three tumors with STK11 mutations and a myxoid background. These data demonstrate that female adnexal tumors of probable Wolffian origin are morphologically and immunohistochemically diverse, but infrequently harbor pathogenic mutations. However, their lack of mutations in contrast to their mimickers may be a valuable tool in diagnostically difficult cases.

BACKGROUND Anaplastic sarcoma of the kidney (ASK) is a rare and newly recognized renal neoplasm. The tumor usually is extensive and cystic, characterized by pleomorphic spindle cells with marked atypia and associated with multinucleated cells. To date, only 27 cases have been reported in the literature. The authors present an additional case and summarize the relevant knowledge in the literature. CASE SUMMARY A 27-year-old previously healthy woman presented with a palpable mass over the abdomen and right flank soreness for one year. After the computed tomography study, the patient underwent right radical nephrectomy obtaining a 1680-g tumor with a size of 18.4 cm × 14.5 cm × 11 cm. The tumor is chiefly composed of anaplastic spindle cells with marked nuclear atypia admixed with multinucleated cells. Immunohistochemical evaluation of tumor cells exhibited diffuse positivity for CD56, p53, and vimentin, and focally positive for desmin. The diagnosis of ASK was established. Unfortunately, a local tumor recurrence followed by a distant metastasis developed within months. The patient died 26 months after the initial surgery. Comparing to the previously 27 cases of ASK, the current case had a relatively worse prognosis, which might be potentially associated with older patient age, larger tumor size, and the lack of en-bloc resection of adjacent organs during the initial radical nephrectomy. CONCLUSION This case points out the featured pathological findings for diagnosing ASK and suggests more aggressive management for patients with ASK.

Over several months, a painless, multinodular, non-erythematous swelling of the deep tissues of his left upper eyelid developed in a 63-year-old man. An excisional biopsy with histopathologic evaluation disclosed a unique sebaceous papilloma within a cyst lined by non-keratinizing squamous epithelium that focally displayed a variably thick, superficial, eosinophilic cuticular layer. Immunohistochemical staining demonstrated that the tumor and its epithelial cystic lining had a profile consistent with Meibomian gland duct epithelium. Adipophilin highlighted cytoplasmic vacuolar lipid positivity. The encapsulation of the lesion, absence of nuclear atypia, and Ki-67 nuclear positivity restricted to the basilar cells established its intrinsically benign nature. The patient's clinical history was remarkable for pulmonary and colonic carcinomas resected, respectively, 20 years and 8 years earlier. DNA mismatch repair protein expression studies disclosed loss of nuclear immunostaining of MSH6 protein, pointing to the possibility of an underlying rare MSH6 variant of the Muir-Torre syndrome, not yet described in the ophthalmic literature. p16 nuclear positivity was also found in the tumor cells, indicating the possible role of high-risk human papillomavirus as an additional factor in the genesis of the tumor. Genetic evaluation of normal and tumoral tissues in future similar cases will detect if there is an underlying germline mutation versus a somatic mutation limited to the tumor. This will be required to fully establish a predictable linkage with this new subtype of the Muir-Torre syndrome.

Ulipristal acetate is a selective progesterone receptor modulator that acts on progesterone receptors in uterine muscle and endometrium. It is effective in reducing the size of uterine leiomyomas (fibroids) and in managing associated menorrhagia. Although ulipristal acetate-associated pathologic changes have been previously documented in the endometrium, it is unclear what morphology can be expected in posttreatment fibroids. We herein report 2 cases in which patients underwent hysterectomy, after at least two 3-mo courses of ulipristal acetate. The fibroids demonstrated some pathologic changes that have previously been described associated with gonadotropin-releasing hormone agonist treatment and other progestogens. In addition, both cases demonstrated plexiform/"patchwork" fibrosis and vascular medial myxoid degeneration. Mitotic activity was absent; however, the presence of ischemic necrosis and mild nuclear atypia may mimic a more aggressive neoplasm in some areas. Awareness of these histopathologic patterns is important in the setting of ulipristal acetate treatment, to avoid over-diagnosis of "uncertain malignant potential" or malignant smooth muscle tumors.

A 35-year-old male, presented with a slow growing painless cutaneous nodule of 1.5 cm size of 6-month duration. On local examination, single well defined, freely mobile, non-tender skin nodule was found over the dorsum of right hand. Fine needle aspiration of the swelling yielded particulate material. The cytosmears were highly cellular and showed three population of cells comprising of cohesive clusters of larger cells, discretely lying larger cells and smaller lymphocyte like cells. (Figure 1) The cohesive cells were larger with round nuclei, pale chromatin and moderate amount of cytoplasm. Focal rosette like arrangement were noted. The larger scattered cells were in the form of naked nuclei with fragile cytoplasm giving a glycogenated appearance to the background. The third population of cells comprised of smaller cells with a coarsely clumped clock face appearing chromatin resembling lymphocytes. There was no mitosis, nuclear atypia or necrosis. (Figure 2).

Syringocystadenocarcinoma papilliferum (SCACP), the malignant counterpart of syringocystadenoma papilliferum (SCAP), is an extremely rare malignant adnexal neoplasm. It is described by the World Health Organization as a malignant transformation of SCAP occurring in middle-aged to elderly individuals with a predilection for the head and neck. SCACP seems to arise from a long-standing syringocystadenoma probably on a background of nevus sebaceous (NS) through a multistep progression. A 75-year-old man was referred to our department with a long-standing NS with a recent newly developing nodule on his scalp. The tumor was excised. On histology, the overall architecture of the tumor still resembled an unusual SCAP within NS but simultaneously showed transition to syringocystadenocarcinoma papilliferum in situ and invasive SCACP as recognizable by the presence of areas of nuclear atypia, increased proliferative activity, and infiltrative growth. In summary, we report an extremely rare case of an invasive SCACP of the scalp that demonstrates histological evidence for all transitive steps in the hypothetical multistep progression from NS to invasive SCACP in one single lesion. The implications of these findings are discussed in the light of the relevant literature.

We report 27 solitary fibrous tumors of the female genital tract emphasizing nonvulvar locations, variant histology, and prognostic factors. The patients ranged from 25 to 78 years (most were over 40), and tumors occurred in the vulva (7), vagina (2), cervix (2), corpus (6), fallopian tube/paratubal soft tissue (5), and ovary (5). They ranged from 1.5 to 39 cm (mean=10.5) cm and were typically solid, but 4 were predominantly cystic. All had a haphazard arrangement of spindled to ovoid cells, with most demonstrating alternating cellular and hypocellular areas and prominent vessels, but 13 lacked hypocellular areas, and 7 had focal diffuse growth with inconspicuous vasculature. Other patterns included corded (8), fascicular (5), trabecular (1), and nested (1). Microcysts (6), myxoid background (8), hyalinization (8), lipomatous differentiation (2), and multinucleated cells (6) were also present, and 10 tumors had necrosis. Vasculature included thin-walled branching "staghorn" (27), thick-walled (7), and hyalinized vessels (5) or dilated anastomosing vascular channels (3). Nuclear atypia ranged from mild (19), moderate (7), to severe (1), and mitoses from 0 to 24/10 HPF (mean=4). STAT6 was positive in all 25 tumors tested. One tumor showed dedifferentiation; the remainder were classified as benign (19) or malignant (7) based on mitotic rate (univariate stratification model) and as low risk (14), intermediate risk (8), or high risk (4) based on the Demicco multivariate risk stratification score. Follow-up (median=23 mo) was available for 16 patients. Six tumors recurred (2 intermediate risk, 3 high risk, and the dedifferentiated tumor), 5 in the abdomen; the dedifferentiated tumor metastasized to the lung. Multivariate risk stratification was superior to univariate classification, as 5 "benign" tumors were reclassified as intermediate risk using the multivariate model; of these, 2 recurred, and 1 patient died of disease. Upper female genital tract tumors occurred in older patients, were larger, and more frequently classified as high risk compared with those of the lower tract. A trend toward increased cellularity was also seen in the upper tract tumors. Only size (P=0.04), necrosis (P=0.04), and Demicco score (P=0.01) independently correlated with recurrence. Female genital tract solitary fibrous tumors demonstrate a wide range of variant morphologies and occur in diverse sites in addition to the vulva. Tumors were often misdiagnosed as other neoplasms; thus, awareness of solitary fibrous tumors occurring at these sites is crucial in prompting staining for STAT6 to establish this diagnosis. The Demicco risk stratification system effectively predicts behavior.

Intravenous leiomyomatosis (IVL) is a quasi-malignant smooth muscle tumor involving lymphatic and venous spaces of the myometrium. Rare cases of IVL with admixed endometrial glands and stroma have been described, termed intravascular adenomyomatosis. We report four additional cases of intravascular adenomyomatosis and expand the clinicopathologic features of these rare tumors. Patients were 39-45 years old and presented with symptoms of dysmenorrhea, postmenopausal bleeding, or pelvic mass. All cases were associated with endometriosis. Three cases comprised intravascular bland smooth muscle tumors with plexiform features, and in some foci, the intravascular tumor contained endometrial type glands and stroma. In one case, there was extensive (10) foci of intravascular adenomyomatosis without evidence of associated smooth muscle neoplasm but did have an endometrial polyp with adenomyomatous features. None of the cases had nuclear atypia, increased mitotic activity, or tumor cell necrosis. The endometrial stromal components were positive for CD10 and negative or weakly positive for desmin by immunohistochemistry. Two cases underwent molecular testing for JAZF1 and PHF1 rearrangements with negative results. Three patients had no evidence of disease at the time of the last follow-up, and one had persistent but stable disease 7 years after incomplete surgical removal and megestrol acetate treatment. Intravascular adenomyomatosis is a variant morphology rarely seen in IVL that lacks characteristic morphologic and molecular features of endometrial stromal sarcoma. Similar to IVL, prognosis is likely linked to completeness of surgical resection. In this study, we found that intravascular adenomyomatosis is frequently associated with endometriosis, a novel finding to add to the literature on this rare IVL variant.

A 50-year-old woman was referred to our hospital for elevated hepatobiliary enzymes. She had a medical history of mastectomy for left breast invasive ductal carcinoma about 10 years ago, and no apparent recurrence had been observed. Contrast-enhanced computed tomography (CT) revealed soft-tissue shadows surrounding the portal vein, celiac artery, and other vessels. The lesions involved the hilar bile duct, and the upstream bile ducts were dilated. Endoscopic retrograde cholangiography showed an obstruction in the hilar bile duct, and biopsies were taken at the site of biliary stenosis. H&E staining showed that cells with strong nuclear atypia and prominent chromatin staining infiltrated in the stroma. Immunohistochemical analysis revealed that the cells were positive for CK7, GATA3 and weakly positive for CK20. Based on these results, we made the diagnosis of biliary stenosis due to retroperitoneal metastasis from breast invasive ductal carcinoma. Biliary inside stents were placed across the biliary stricture, and she received chemotherapy plus endocrine therapy for breast cancer. So far, the partial response has been maintained for 1 year since the diagnosis of retroperitoneal metastasis. Although retroperitoneal metastasis from breast cancer, especially breast invasive ductal carcinoma, is extremely rare, it could be a differential diagnosis for biliary stenosis.

Introduction/Background* Benign metastasizing leiomyoma (BML) is a rare benign condition involving the extra-uterine spread of smooth muscle cells with histological, immunological, and molecular patterns similar to those of benign uterine leiomyomas. Due to the uncommon nature of the disease, diagnosis and treatment is very challenging. There are no current standardized guidelines for treatment of BML but usually treated with a combination of surgical resection and radiotherapy, followed by hormonal treatment and monitored through radiography. Methodology This is a case of a 49 year old G0 with an incidental finding of BML in the lungs. Routine pre-employment chest x-ray revealed pulmonary nodules. Computed tomography (CT) scan of the abdomen revealed uterine leiomyoma. Video-assisted thoracic surgery (VATS) with wide resection of pulmonary nodules and frozen section was done. Histopathology revealed BML. Immunostains for p53, Ki-67 and p16 were negative, while immunostain for estrogen and progesterone receptor (ER/PR) were positive. Serial chest radiography monitoring showed no significant interval change in pulmonary nodules and patient remained asymptomatic. Few years later, the patient presented an enlarged abdomen. Transvaginal ultrasound revealed a pedunculated subserous myoma. The patient underwent exploratory laparotomy, extrafascial hysterectomy with bilateral salpingooophorectomy. Histopathology revealed BML. Result(s)* Currently, patient has been asymptomatic for 6 years with no interval changes in pulmonary nodules size despite having multiple lesions in both lungs. Conclusion* BML is a monoclonal benign tumor with high metastatic potential. A hormone dependent, which growth depends primarily on estrogen and progesterone. This can metastasize to distant organs commonly in the lung (PBML), hence, confused with leiomyosarcoma. Uterine surgeries such as curettage, hysteromyomectomy and hysterectomy can cause it to spread hematogenously to the lung through venous circulation. Patients are usually asymptomatic at presentation and lesions are only incidentally discovered during routine physical examinations as multiple pulmonary nodules in chest radiography. Thoracoscopic lung biopsy remains the gold standard in the diagnosis for PBML. The most helpful pathologic features that characterize PBML and other BMLs are their low cellularity and mitotic index, and the absence of nuclear atypia and tumor necrosis. Immunohistochemistry staining usually is positive for Desmin, Smooth Muscle Actin (SMA) and ER/PR.

Introduction/Background* To assess the clinicopathological features, prognostic factors, and survival rates associated with uterine leiomyosarcoma (uLMS). Methodology Databases from 15 participating gynecological oncology centers in Turkey were searched retrospectively for women who had been treated for stage I-IV uLMS between 1996 and 2018. Result(s)* Of 302 consecutive women with uLMS, there were 234 patients with Federation of Gynecology and Obstetrics (FIGO) stage I disease and 68 with FIGO stage II-IV disease. All patients underwent total hysterectomy. Lymphadenectomy was performed in 161 (54.5%) cases. A total of 195 patients received adjuvant treatment. The 5-year disease-free survival (DFS) and overall survival (OS) rates were 42% and 54%, respectively. Presence of lymphovascular space invasion (LVSI), higher degree of nuclear atypia, and absence of lymphadenectomy were negatively correlated with DFS, while LVSI, mitotic count, higher degree of nuclear atypia, FIGO stage II-IV disease, and suboptimal surgery significantly decreased OS. Conclusion* LVSI and higher degree of nuclear atypia appear to be prognostic indicators for uLMS. Lymphadenectomy seems to have a significant effect on DFS but not on OS.

We present histopathological criteria for diagnosing keratoacanthoma (KA). In KA, four histological stages are recognized, which are the early/proliferative stage, well-developed stage, regressing stage and regressed stage. In diagnosing KA, we emphasize that KA consists of the proliferation of enlarged pale pink cells with ground glass-like cytoplasm without nuclear atypia, other than crateriform architecture. KA sometimes exhibits malignant transformation within the lesions. We describe the characteristics of benign and malignant epithelial crateriform tumors that should be differentiated from KA. We also present the data of histopathological diagnosis of lesions clinically diagnosed as KA, its natural course and related lesions after partial biopsy, and incidence of crateriform epithelial neoplasms. Based on these data, we recommend complete excision of the lesion when KA is clinically suspected, especially when the lesion is located on a sun-exposed area of an elderly patient. If complete excision is impossible, partial excision of a sufficient specimen with intact architecture is required. In such a case, however, careful investigation after biopsy will be needed, even if the histopathological diagnosis is KA, because there is some possibility that a conventional SCC lesion remains in the residual tissue.

Placental site nodule (PSN) is a benign proliferation of chorionic-type intermediate trophoblastic cells that forms a tumor-like lesion. Most PSNs are intrauterine, but a few have been reported outside the uterus, including in fallopian tubes. PSN is related to epithelioid trophoblastic tumor (ETT) in that both are composed of chorionic-type intermediate trophoblastic cells, while ETT is hypercellular and contains trophoblastic cells with increased nuclear atypia and a higher Ki-67 proliferation index as compared with PSN. Occasionally, an intermediate stage between a PSN and an ETT is observed, and such a lesion is often recognized as an atypical PSN (aPSN) characterized by trophoblastic cells exhibiting morphologic features in transition from a conventional PSN to an ETT. aPSN has been thought to exhibit benign behavior; however, it has also been reported that up to 15% of aPSN lesions either coexist with, or subsequently develop into, ETT. To the best of our knowledge, there has been no case report of an aPSN in an extrauterine site. Here, we reported a highly unusual case of tubal aPSN, which illustrates several key features associated with PSN and its possible pathogenesis.

To investigate the histological diversity of salivary mucoepidermoid carcinoma (MEC), its clinicopathological features, and its associations with CRTC1/3-MAML2 fusions.Salivary MEC cases (n = 177) were examined for CRTC1/3-MAML2 fusions, histological variants were classified, and tumours were graded according to four different grading systems. Adverse histological features considered to be unusual in MEC were also investigated. Of the 177 MEC cases, 110 were positive for CRTC1/3-MAML2 fusions. The classical variant was the most frequent in the fusion-positive case group, the fusion-negative case group, and the total case group. The clear/oncocytic variant was the second most frequent in the fusion-positive and total case groups. Oncocytic, Warthin-like and spindle variants were seen in the fusion-positive case group only. Clear cell, sclerosing, mucinous and central variants were seen in both the fusion-positive case group and the fusion-negative case group. No case was classified as a ciliated variant, as a mucoacinar variant, or as a high-grade transformation. As compared with the classical variant, non-classical variants were characterised by frequent CRTC1/3-MAML2 fusions and a low clinical stage in all cases. Of the four histological features considered to be unusual in MEC, marked nuclear atypia, frequent mitoses (10/10 high-power fields) and extensive necrosis were found independently of the fusion status, and were present in 3-5% of all cases. However, none of the cases showed overt keratinisation. On comparison, the Armed Forces Institute of Pathology and modified Healey grading systems downgraded tumours, the Brandwein system upgraded tumours, and the Memorial Sloan Kettering system provided a moderate means of assessment.Recognition of the histological diversity of MEC, its clinicopathological features and its associations with CRTC1/3-MAML2 fusions is helpful for an accurate diagnosis of this carcinoma.

Introduction: Fibroadenomas (FAs) and phyllodes tumors (PTs) are less prevalent but allied to have malignant transformation in many instances. It is a challenge to diagnose the phyllodes by conventional trucut biopsy technique. Objective: To evaluate the histological characteristics of tumors labeled as fibroepithelial lesions of breast tissues on trucut biopsy and compare with a diagnosis on excision biopsy. Methods and materials: It was a descriptive cross-sectional study that was carried out in Shaukat Khanum Memorial Hospital and Research Centre within six years from January 2015 to January 2021. In trucut samples, stromal cellularity, stromal cell nuclear atypia, mitotic count, stromal overgrowth, the enhancement of stromal cellularity adjacent to epithelium were scrutinized. In each category, the activity was seen as absent, mild, moderate, or severe. Mitotic activity was graded as 0-1, 0-5, 5-10, >10. Results: A total of 125 patients were registered for the study. The mean age of patients in our study was 33.86 ± 9.95 years. The mean size was 41.02 ± 27.38 mm with a mean lump duration of 7.52 ± 5.34 months. In the FA group, the trucut sampling report showed the stromal cellularity as mild in 62 (69.7%) and stromal cell nuclear atypia as absent in 68 (76.4%) cases. But in the phyllodes tumor group, the stromal cellularity was severe in 10 (27.8%) patients and stromal cell nuclear atypia was severe in five (13.9%). The ultimate outcome showed that 89 (71.2%) patients had FA and 36 (28.8%) had PT at excision. Conclusion: Assessment of tumor size, stromal cellularity, mitoses, and enhancement of stromal cellularity adjacent to epithelium are useful markers for diagnosing the PT in trucut needle biopsy.

Primary peritoneal mucinous adenocarcinoma is rare in men. The low‐grade tumor consisted of mucin‐producing columnar cells with minimal nuclear atypia. Relationship to pseudomyxoma peritonei and disseminated peritoneal adenomucinosis is discussed.

Myoepithelial tumor (MET) of bone is an unusual tumor of uncertain differentiation and histogenesis. Although its presence in various bones has been reported sparsely, the presentation in clivus as primary myoepithelial carcinoma (MEC) has never been reported. They resemble their salivary gland counterparts morphologically and immunohistochemically, but harbor distinct molecular phenotype. At present, moderate nuclear atypia is the acceptable criteria to differentiate MEC from myoepithelioma. Because of their rarity, wide histopathological spectrum, and intraosseous location, MET of bone is easily confused with a variety of primary bone and cartilaginous tumors. Application of immunohistochemistry and, if required, molecular testing are required for making a correct diagnosis. In this article, we describe an extremely rare case of a primary MEC arising from the clivus, which owing to unusual location and immunohistochemical profile was diagnostically challenging.

PEComa (PEC tumours; perivascular epithelioid cell tumours) is a family of rare tumours of mesenchymal origin, consisting of epithelial perivascular cells expressing melanocytic and myioid markers. This group includes benign tumours — such as angiomyolipoma (AML) of the kidney, and poorly differentiated malignant PEComa tumours with potential for an aggressive clinical course, which is the main focus of this review. PEComas are most often diagnosed in middle-aged women as extensive tumours located in the abdominal cavity or pelvis, manifesting as pain and complaints related to pressure on nearby organs. PEComa tumours should be differentiated from gastrointestinal stromal tumours (GIST), leiomyosarcoma, melanoma metastasis, chromophobic renal cell carcinoma, clear cel sarcoma, and other clear cell component tumours. Somatic inactivating mutations within the TSC1/TSC2 genes, resulting in excessive activation of the mTORC1 complex, are characteristic for this group of tumour. Recently, a separate PEComa subgroup has been distinguished, characterised by the presence of the TFE3 gene fusion, which also causes increased activity of the mTOR signalling pathway. Negative prognostic factors that indicate an increased risk of PEComa malignant biology are most often: tumour size > 5 cm, increased cytological and nuclear atypia, infiltration of surrounding tissues and blood vessels, presence of necrosis, and high mitotic activity. Radical resection remains the primary treatment method for PEComas because these tumours are characterised by high resistance to radiation and chemotherapy. In the case of locally advanced or metastatic disease, only single reports of short-term responses to palliative chemotherapy containing doxorubicin, gemcitabine, or ifosfamide are available in the literature. There are an increasing number of reports, in the form of several case reports and a few retrospective analyses, about the potential effectiveness of using mTOR inhibitors in unresectable cases. These drugs result in a reduction in primary tumour size and metastasis, as well as symptom relief, with controllable side effects. Unfortunately, case reports of complete resistance to mTOR inhibitor therapy are also available.

The classification of indeterminate cytopathology at thyroid fine-needle-aspiration (FNA) has been updated to reduce the number of unnecessary surgery; the 2014 Italian classification introduced the low-risk (TIR3A) and high-risk (TIR3B) subcategories. Aim of this study was to identify the ultrasonographic (US), clinical and cytological predictors of malignancy among TIR3B nodules from a single institution. A prospective observational study including 1844 patients who underwent thyroid FNA from June 2014 to January 2019. Ultrasonographic, clinical and cytological features were recorded. All TIR3B diagnoses were referred to surgery. According to final histology, patients were divided into thyroid cancer (TC) or benign nodules. Chi-square test, or Fisher exact test when appropriate, were used to compare groups and logistic regression analyses were used to determine independent predictors of malignancy. Of 1844 FNAs, 96 (5.2%) were TIR3B. Histology report was available in 65. Among them, 25 (38.5%) were TC. Predictors of TC were nodule size