Uterine Mesenchymal Tumors: Updates on Pathology, Molecular Landscape, and Therapeutics.

Background: Mesenchymal uterine tumors are a diverse group of neoplasms with varying biological potential. Many of these neoplasms can have overlapping morphologic similarities, which, in some instances, render their diagnosis and categorization thorough histomorphologic examination inconclusive. In the last decade, an exponential amount of molecular data aiming to more accurately characterize and, consequently, treat these tumors have accumulated. Objective: The goal of this narrative review is to provide a pathologic review, a genetic update, and to know the new therapeutic avenues of primary uterine mesenchymal neoplasms.

Association between Endometriosis and the Risk of Ovarian, Endometrial, Cervical, and Breast Cancer: A Population-Based Study from the U.S. National Inpatient Sample 2016-2019.

OBJECTIVE: We investigated the potential relationship between endometriosis and risk of ovarian, endometrial, cervical, and breast cancers using the National Inpatient Sample (NIS) database. METHODS: We utilized the International Classification of Diseases (ICD-10) system to identify relevant codes from the NIS database (2016-2019). Univariate and multivariate regression analyses (adjusted for age, race, hospital region, hospital teaching status, income Zip score, smoking, alcohol use, and hormonal replacement therapy) were conducted to evaluate the association between endometriosis and gynecologic cancers and summarized as odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: In the examined dataset, there were 1164 and 225,323 gynecologic cancer patients with and without endometriosis, respectively. Univariate analysis showed endometriosis was significantly associated with a higher risk of ovarian (OR = 3.42, 95% CI: 3.05-3.84, p < 0.001) and endometrial (OR = 3.35, 95% CI: 2.97-3.79, p < 0.001) cancers. There was no significant association between endometriosis and cervical cancer (OR = 1.05, 95% CI: 0.85-1.28, p = 0.663). Interestingly, endometriosis was significantly associated with a low risk of breast cancer (OR = 0.12, 95% CI: 0.10-0.17, p < 0.001). Multivariate analysis after Bonferroni correction (p < 0.006) showed that endometriosis was significantly associated with a high risk of ovarian (adjusted OR = 3.34, 95% CI: 2.97-3.75, p < 0.001) and endometrial (adjusted OR = 3.61, 95% CI: 3.12-4.08, p < 0.001) cancers. Conversely, there was no significant association between endometriosis and cervical cancer (OR = 0.80, 95% CI: 0.65-0.99, p = 0.036). CONCLUSIONS: Patients with endometriosis exhibited unique gynecologic cancer risk profiles, with higher risks for ovarian and endometrial cancers, and no significant risk for cervical cancer. The observed connection between endometriosis and a reduced risk of breast cancer remains a perplexing phenomenon, which cannot be put into context to date.

A case of neonatal osteofibrous dysplasia with novel CDK12 and DDR2 mutations.

Osteofibrous dysplasia [OFD] is a rare, benign pediatric fibro-osseous lesion that exclusively arises in the lower limbs. Apart from the limited number of familial OFD cases with MET mutation, no other genetic aberrations have been identified. Herein, we report a case of OFD in a four-month- old girl's leg with novel cyclin-dependent kinase 12 and discoidin domain receptor 2 gene mutations. Further studies to understand their role in the pathogenesis and clinical utility are needed.

Gangliocytic Paraganglioma: A Rare Etiology of Obstructive Jaundice.

BACKGROUND Gangliocytic paraganglioma is an extremely rare tumor, with only 263 reported cases. This tumor has heterogeneous clinical presentation, with gastrointestinal bleeding being the most common. However, jaundice is a relatively unusual presentation, seen in less than 5% of all cases. CASE REPORT We report the case of a 32-year-old man who presented with abdominal pain and jaundice. He reported having similar episodes of this pain recently, but they were milder in severity. On examination, there was a tenderness in the right upper quadrant with a positive Murphy sign. Laboratory investigation revealed total bilirubin of 3.6 mg/dL with a direct bilirubin of 3.0 mg/dL, alkaline phosphatase of 323 IU/L, and g-glutamyltransferase level of 1153 IU/L, giving the impression of obstructive jaundice. The abdominal ultrasound examination revealed a normal common bile duct diameter with no thickening or pericholecystic fluid noted. Subsequently, the patient underwent endoscopic retrograde cholangiopancreatography, which revealed a mass in the second part of the duodenum. Histopathological examination of biopsy specimens obtained by fine-needle biopsy revealed an unencapsulated submucosal lesion with epithelioid, spindle, and ganglion cells. The spindle cells expressed positive immunohistochemical staining for S100, synaptophysin, and chromogranin. These findings were consistent with the diagnosis of gangliocytic paraganglioma. Surgical resection of the tumor was advised. However, the patient refused the operation despite the recommendation of the oncology team. CONCLUSIONS Gangliocytic paraganglioma is a very rare tumor that may present with a clinical picture mimicking a biliary disease. Clinicians should have a high index of suspicion for duodenal lesions in patients presenting with obstructive jaundice with no evidence of biliary stones.

Atypical Presentation of Salzmann Nodule: A Case Report and Literature Review.

Salzmann's nodular degeneration (SND) is an unusual corneal condition that is slowly progressive and non-inflammatory in nature. It results in millimetric gray-white to bluish nodules formation anterior to Bowman's layer of the cornea. It usually affects both eyes in 80% of the cases. These elevated nodules are located near the limbus or in the mid-peripheral cornea, with some exceptions. Salzmann nodule develops following corneal trauma or inflammation. However, it can present idiopathically. Here, we report an atypical case of idiopathic symptomatic large central SND that was treated successfully with superficial keratectomy.

Protein expression profile and prevalence pattern of the molecular classes of breast cancer--a Saudi population based study.

BACKGROUND: Breast cancer is not a single entity but a diverse group of entities. Advances in gene expression profiling and immunohistochemistry as its surrogate marker have led to the unmasking of new breast cancer molecular subtypes, resulting in the emergence of more elaborate classification systems that are therapeutically and prognostically more predictive. Molecular class distribution across various ethnic groups may also reveal variations that can lead to different clinical outcomes in different populations. METHODS: We aimed to analyze the spectrum of molecular subtypes present in the Saudi population. ER, PR, HER2, EGFR and CK5/6 were used as surrogate markers for gene expression profiling to classify 231 breast cancer specimens. Correlation of each molecular class with Ki-67 proliferation index, p53 mutation status, histologic type and grade of the tumor was also carried out. RESULTS: Out of 231 cases 9 (3.9%) were classified as luminal A (strong ER +ve, PR +ve or -ve), 37 (16%) as luminal B (weak to moderate ER +ve, and/or PR +ve), 40 (17.3%) as HER2+ (strong or moderately positive HER 2 with confirmation by silver enhanced in-situ hybridization) and 23 (10%) as basal (CK5/6 or EGFR +ve). Co-positivity of different markers in varied patterns was seen in 23 (10%) of cases which were grouped into a hybrid category comprising luminal B-HER2, HER2-basal and luminal-basal hybrids. Ninety nine (42.8%) of the tumors were negative for all five immunohistochemical markers and were labelled as unclassified (penta negative). A high Ki-67 proliferation index was seen in basal (p=0.007) followed by HER2+ class. Overexpression of p53 was predominantly seen in HER2+(p=0.001) followed by the basal group of tumors. A strong correlation was noted between invasive lobular carcinoma and hormone receptor expression with 8 out of 9 lobular carcinoma cases (88.9%) classifiable as luminal cancers. Otherwise, there was no association between the molecular class and the histologic type or grade of the tumor. CONCLUSIONS: Subtyping by use of this immunohistochemical panel revealed a prevalence pattern that is unique to our population; luminal tumors comprised only 19.9%, and the unclassified group (penta negative) 42.8%, a distribution which is distinctive to our population and in contrast with all Western studies. The presence of a predominant unclassified group also suggests that the currently used molecular analytic spectrum may not completely encompass all molecular classes and there is a need to further refine and develop the existing classification systems.