Therapeutic management of uterine tumours resembling ovarian sex cord tumours including a focus on fertility: A systematic review.

OBJECTIVE: Uterine tumours resembling ovarian sex cord tumours (UTROSCTs) are extremely rare. To date, most patients with UTROSCTs have undergone hysterectomy and had a benign clinical course. Fertility-preserving surgery should be considered because some patients with UTROSCTs are aged < 40 years. This paper reviews the treatment and prognosis for patients with UTROSCTs, with a focus on fertility. METHODS: PubMed, MEDLINE and Scopus were searched systematically for case reports and case series of UTROSCTs published in English from inception to December 2022, and initial treatment and recurrence rates were compared. The following data were extracted: age; symptoms; initial therapy; metastasis at diagnosis; disease-free survival (DFS); and recurrence. RESULTS: In total, 147 patients (72 studies) reporting the clinical course of UTROSCTs were analysed. The median age at diagnosis was 50 years, and 28 (19.0 %) patients were aged < 40 years. Most patients (n = 125, 85.0 %) underwent hysterectomy as the initial surgery, with a recurrence rate of 17.6 % (n = 22). The recurrence rate was 30 % (n = 6) in patients who underwent mass resection (n = 20). Among the 15 patients who underwent mass resection aged < 40 years, seven went on to achieve pregnancy (46.7 %) and six had successful deliveries (40.0 %). No significant differences in 5- and 10-year DFS were found between the hysterectomy and mass resection groups (p = 0.123 and 0.0612, respectively). Bilateral salpingo-oophorectomy in addition to hysterectomy was not significantly associated with 10-year DFS (p = 0.548). CONCLUSION: While total hysterectomy is the recommended treatment for UTROSCTs based on recurrence rates, mass resection is an acceptable treatment option for patients who wish to retain their childbearing potential. It is recommended that these women should plan for pregnancy and delivery as soon as possible after mass resection, and should undergo hysterectomy within 5 years.

Uterine Tumor Resembling Ovarian Sex Cord Tumor: A Case Report.

Uterine tumors resembling ovarian sex cord tumors (UTROSCTs) are extremely rare, occurring in less than 1% of uterine stromal tumors, and they are considered to have a low malignant potential. Due to the small number of cases, no standard treatment has been defined. A 77-year-old woman with postmenopausal bleeding was admitted to our department. Imaging studies revealed a substantial mass around 30 mm in size on the anterior uterine wall. A total hysterectomy and bilateral salpingo-oophorectomy were performed for further diagnosis and treatment. The tumor revealed histopathological findings of a sex cord-like growth pattern in the form of fascicles, cords, or small nests. Immunohistochemical findings revealed that the tumor cells were positively reactive to alpha-SMA, calretinin, CD99, estrogen receptor, and progesterone receptor, collectively diagnosed as UTROSCT. No recurrence was observed over 12 months after treatment. We experienced the treatment of UTROSCT, an extremely rare tumor that occurs in elderly women. Although most cases of UTROSCT have a benign clinical course, several cases of recurrence and metastasis have been reported. It should be followed up for a long term after treatment.

Rapidly Progressing Anaplastic Carcinoma of the Pancreas with Mucoepidermoid Carcinoma: An Autopsy Case Report.

A 75-year-old man visited our hospital for the examination of a tumor in the pancreas. Computed tomography showed an 85×85-mm low-density tumor in the pancreas. The tumor was pathologically diagnosed as poorly differentiated carcinoma by endoscopic ultrasound-guided fine-needle aspiration. Although we started chemotherapy, the patient died 84 days after the diagnosis. An autopsy demonstrated a ruptured anaplastic carcinoma with mucoepidermoid carcinoma of the pancreas. Anaplastic carcinoma with mucoepidermoid carcinoma is a very rare histologic subtype of pancreatic carcinoma, so pathological findings are important for predicting the patient's prognosis. Physicians should be aware of this rare but fatal disease.

Nuclear expression of MDM2 in hibernoma: a potential diagnostic pitfall.

Hibernoma is a rare benign adipocytic tumor composed of a proliferation of brown and white fat cells varying in their proportions. The tumor may also contain fat cells resembling lipoblasts, which makes it difficult to distinguish it from atypical lipomatous tumor/well differentiated liposarcoma (ALT/WDLS). Although nuclear expressions of murine double minute 2 (MDM2) and cyclin-dependent kinase 4 (CDK4) are widely used as immunohistochemical surrogate markers for ALT/WDLS, the utility of these proteins in distinguishing between hibernoma and ALT/WDLS still remains to be elucidated. We evaluated immunohistochemical expressions of MDM2 and CDK4 in 10 hibernomas expressing uncoupling protein-1 (UCP-1), a mitochondrial protein transporter consistently expressed in brown fat cells, and lacking MDM2 gene amplification, which was analyzed by fluorescence in situ hybridization (FISH). In contrast to the data previously obtained, nuclear expression of MDM2 was observed in 100% (10/10 cases) of the hibernomas irrespective of the proportion of brown fat cells, whereas no cases were positive for CDK4. The tumors also showed almost concurrent expression of p53 (in 9/10 cases) and ubiquitin-specific-processing protease 7 (USP7) (in 10/10 cases), which deubiquitinates and stabilizes MDM2, potentially resulting in its nuclear expression without MDM2 gene amplification. MDM2 expression may thus be a diagnostic pitfall for hibernoma particularly in differentiating it from ALT/WDLS.

Difficulty of treatment for pleural epithelioid hemangioendothelioma: a report of a case.

We herein report the case of a 62-year-old man who underwent extrapleural pneumonectomy (EPP) for pleural epithelial hemangioendothelioma (EHE) diagnosed by a pleural biopsy. Pre-operative computed tomography revealed diffuse pleural thickening and pleural effusion in the right thoracic cavity, although metastasis to neither the lymph nodes nor distant organs was detected. We decided to perform EPP based on surgical findings that the tumor had invaded the lung parenchyma. A pathological examination revealed tumor invasion of the lung parenchyma, blood vessel, pericardium, diaphragm and bronchial wall. Despite aggressive treatment, tumor recurrence was detected about 1 month after surgery. Although we controlled the tumor progression using pazopanib, the patient ultimately died 3.5 months after the operation. Pleural EHE is a very rare disease that has a poor prognosis due to its high malignant potential. It is important to formulate strategies matched to individual cases based on disease progression and invasiveness of treatment.

MUC4 expression in meningiomas: under-recognized immunophenotype particularly in meningothelial and angiomatous subtypes.

AIMS: MUC4 is a transmembrane glycoprotein that plays a role in cell growth signalling and is expressed in various epithelial tissues. Gene expression profiling and immunohistochemical analyses revealed that MUC4 is also constantly and specifically expressed in low-grade fibromyxoid sarcomas and sclerosing epithelioid fibrosarcomas among the mesenchymal tumours, and immunohistochemical detection of MUC4 is extremely useful for their diagnoses. In our routine pathological practice, we noticed that meningiomas are also often positive for MUC4, which has not yet been reported previously, despite the extensive scrutiny of its expression in soft tissue tumours. METHODS AND RESULTS: We examined immunohistochemically the expression of MUC4, progesterone receptor (PgR) and somatostatin receptor 2A (SSTR2A) in 140 meningiomas of various histological subtypes and 123 other mesenchymal tumours, including intracranial or sinonasal tumours and peripheral nerve sheath tumours. MUC4 was expressed in 130 meningiomas (92.9%). MUC4 expression was constant and almost diffuse in meningothelial and angiomatous subtypes, whereas it was limited in 5% or fewer tumour cells or absent in 26 of 28 fibrous meningiomas. All other mesenchymal tumours examined were negative for MUC4. PgR and SSTR2A were expressed in 94 (67.1%) and 134 (95.7%) meningiomas, respectively. Five of six SSTR2A-negative meningiomas focally expressed MUC4. CONCLUSIONS: MUC4 is expressed variably but almost consistently in meningiomas, particularly in meningothelial or angiomatous subtypes. Its immunohistochemical detection is useful to distinguish meningiomas from other intracranial or head and neck mesenchymal tumours, particularly those with epithelioid features. Our study could expand a variety of MUC4-positive mesenchymal tumours.

Inhibition of WNT/ß-catenin signaling under serum starvation and hypoxia induces adipocytic transdifferentiation in human leiomyoma cells.

Fatty metamorphosis is an uncommon alteration in uterine leiomyoma (i.e., lipoleiomyoma), and the pathogenetic mechanisms underlying this phenomenon remain poorly understood. Because a conditional deletion of ß-catenin, a major transducer of the canonical Wingless/integrated (WNT) pathway, in the developing mouse uterus can induce adipogenesis in the myometrium, it is hypothesized that inhibition of the WNT/ß-catenin signaling may be also involved in the development of fat cells within uterine leiomyoma. In the current study, which was performed to address this point, intracytoplasmic lipid droplets were detectable in cultured human leiomyoma cells by treatment with a potent tankyrase inhibitor, XAV939, which antagonizes ß-catenin, in a serum-starved culture medium without additional adipogenesis-inducing agents or supplements, and showed increasing accumulation in a time-dependent manner. In addition, the induction of fat cells was greatly enhanced under hypoxic conditions (i.e., 2.5% O2)-recapitulating the local in vivo situation of uterine leiomyoma-in comparison to that under normoxic conditions (i.e., 21% O2). The marker genes of differentiated fat cells such as ADIPOQ and PLIN were highly expressed in leiomyoma cells that were treated with XAV939 under hypoxia and serum starvation, whereas the immunohistochemical expression of desmin-a cytoskeletal protein representing smooth muscle differentiation-was downregulated, which appears in line with the switch in differentiation. The results of our study suggest that the inhibition of canonical WNT/ß-catenin signaling under the stress due to hypoxia and serum starvation can initiate adipocytic transdifferentiation or metaplasia in human uterine leiomyoma cells, which is potentially related to the development of lipoleiomyoma.

Lanthanum-Induced Mucosal Alterations in the Stomach (Lanthanum Gastropathy): a Comparative Study Using an Animal Model.

Lanthanum (La) carbonate (LC) is one of the most potent phosphate binders that prevents the elevation of serum phosphate levels in patients with end-stage renal diseases undergoing dialysis. LC binds strongly to dietary phosphate and forms insoluble complexes that pass through the gastrointestinal tract. La deposition in patients treated with LC is a recently documented finding particularly observed in gastric mucosa. We herein describe the detailed gastric mucosal lesions in 45 LC-treated patients and address the potential underlying pathologic mechanism using oral LC administration in rats. Microscopically, La deposition, as shown by subepithelial collections of plump eosinophilic histiocytes or small foreign body granulomas containing coarse granular or amorphous inclusion bodies, was found in the gastric mucosa of 44 (97.8%) of the 45 dialysis patients in the study cohort, which was most frequently associated with foveolar hyperplasia (37.8%). Using oral administration of rats with 1000 mg/day LC for 2 or more weeks, La deposition was consistently detectable in the gastric mucosa but not in other organs examined. In addition, various histologic alterations such as glandular atrophy, stromal fibrosis, proliferation of mucous neck cells, intestinal metaplasia, squamous cell papilloma, erosion, and ulcer were demonstrated in the rat model. Thus, orally administered LC can induce mucosal injury, designated here as La gastropathy, which may alter the local environment and result in La deposition in the gastric mucosa, thereby potentially inducing abnormal cell proliferation or neoplastic lesions.

Retroperitoneal dedifferentiated liposarcoma with huge cystic degeneration: A case report.

Prominent cyst formation is an unusual feature of liposarcoma. We report here a case of dedifferentiated liposarcoma with huge cystic change without preoperative chemo- or radiation therapy. The lesion arose in the retroperitoneum juxtaposed to the right kidney of a 67-year-old woman. She underwent a surgical removal of the retroperitoneal cyst. The cystic tumor contained 1600 mL of old bloody fluid, and its wall was composed of edematous, inflamed or sclerosing fibrous tissue with fatty tissue containing abundant atypical stromal cells, which were immunohistochemically positive for MDM2 and CDK4, and demonstrated MDM2 gene amplification by fluorescence in situ hybridization. The wall was contiguous to an atypical lipomatous nodule located in the mesentery. The following surgical specimens of the right hemicolectomy and right nephrectomy revealed atypical cells infiltrating into the subserosa of the colon and the perirenal fat tissue or that in the renal sinus. This case indicates that well differentiated or dedifferentiated liposarcoma should be also considered as a differential diagnosis of perirenal cystic mass.