PEC-PRO: A new prognostic score from a series of 87 patients with localized perivascular epithelioid cell neoplasms (PEComas) treated with curative intent.

BACKGROUND: Perivascular epithelioid cell neoplasms (PEComas) encompass a heterogeneous family of mesenchymal tumors. Previously described clinicopathologic features aimed at distinguishing benign from malignant variants but lacked prognostic value. METHODS: This retrospective analysis examined clinicopathologic data from patients who had localized PEComa across French Sarcoma Network centers. The authors analyzed 12 clinicopathologic features in a Cox proportional hazard framework to derive a multivariate prognostic risk model for event-free survival (EFS). They built the PEComa prognostic score (PEC-PRO), in which scores ranged from 0 to 5, based on the coefficients of the multivariate model. Three groups were identified: low risk (score = 0), intermediate risk (score = 1), and high risk (score ≥ 2). RESULTS: Analyzing 87 patients who had a median 46-month follow-up (interquartile range, 20-74 months), the median EFS was 96.5 months (95% confidence interval [CI], 47.1 months to not applicable), with 2-year and 5-year EFS rates of 64.7% and 58%, respectively. The median overall survival was unreached, with 2-year and 5-year overall survival rates of 82.3% and 69.3%, respectively. The simplified Folpe classification did not correlate with EFS. Multivariate analysis identified three factors affecting EFS: positive surgical margins (hazard ratio [HR], 5.17; 95% CI, 1.65-16.24; p = .008), necrosis (HR, 3.94; 95% CI, 1.16-13.43; p = .030), and male sex (HR, 3.13; 95% CI, 1.19-8.27; p = 0.023). Four variables were retained in the prognostic model. Patients with low-risk PEC-PRO scores had a 2-year EFS rate of 93.7% (95% CI, 83.8%-100.0%), those with intermediate-risk PEC-PRO scores had a 2-year EFS rate of 67.4% (95% CI, 53.9%-80.9%), and those with high-risk PEC-PRO scores had a 2-year EFS rate of 2.3% (95% CI, 0.0%-18.3%). CONCLUSIONS: The PEC-PRO score reliably predicts the risk of postoperative recurrence in patients with localized PEComa. It has the potential to improve follow-up strategies but requires validation in a prospective trial.

Five cases of uterine perivascular epithelioid cell tumors (PEComas) and review of literature.

OBJECTIVES: Perivascular epithelioid cell tumor (PEComa) is a rare condition and the recognition of this condition is limited. Here we report five cases of uterine PEComa to add to the limited understanding of this rare condition. METHODS: Five cases from Obstetrics and Gynecology Hospital of Fudan University were diagnosed as uterine PEComas. We collected the patients' clinical and pathological data as well as their outcomes. RESULTS: All the five cases were diagnosed post-operationally. Fertility-sparing surgery was done for the first case and had a mass resection only. She delivered a healthy boy through the cesarean section in November 2016 and neither recurrence nor metastasis was found for 71 months. Hysterectomy was done for the other four cases. Adjuvant chemotherapy was also given for case 2 and case 4. Case 2 had combined endometrial cancer, which could be associated with tuberous sclerosis complex (TSC). She was followed up for 22 months and neither recurrence nor metastasis was detected. Neither recurrence nor metastasis was found in case 3 for 33 months. However, the patient in case 4 died of multiple dissemination and multiple organs failures, 10 months after the second surgery. The patient in case 5 had the hysterectomy and left adnexal resection and in this case we had no data about her long-term outcomes. CONCLUSION: It is still challenging to detect and diagnose uterine PEComa clinically and no consensus or guidelines have been established regarding the treatment of this condition. More case studies are needed to enlighten the underlying mechanism and help optimize the therapies for this condition.

PSF/SFPQ is a very common gene fusion partner in TFE3 rearrangement-associated perivascular epithelioid cell tumors (PEComas) and melanotic Xp11 translocation renal cancers: clinicopathologic, immunohistochemical, and molecular characteristics suggesting classification as a distinct entity.

An increasing number of TFE3 rearrangement-associated tumors, such as TFE3 rearrangement-associated perivascular epithelioid cell tumors (PEComas), melanotic Xp11 translocation renal cancers, and melanotic Xp11 neoplasms, have recently been reported. We examined 12 such cases, including 5 TFE3 rearrangement-associated PEComas located in the pancreas, cervix, or pelvis and 7 melanotic Xp11 translocation renal cancers, using clinicopathologic, immunohistochemical, and molecular analyses. All the tumors shared a similar morphology, including a purely nested or sheet-like architecture separated by a delicate vascular network, purely epithelioid cells displaying a clear or granular eosinophilic cytoplasm, a lack of papillary structures and spindle cell or fat components, uniform round or oval nuclei containing small visible nucleoli, and, in most cases (11/12), melanin pigmentation. The levels of mitotic activity and necrosis varied. All 12 cases displayed moderately (2+) or strongly (3+) positive immunoreactivity for TFE3 and cathepsin K. One case labeled focally for HMB45 and Melan-A, whereas the others typically labeled moderately (2+) or strongly (3+) for 1 of these markers. None of the cases were immunoreactive for smooth muscle actin, desmin, CKpan, S100, or PAX8. PSF-TFE3 fusion genes were confirmed by reverse transcription polymerase chain reaction in cases (7/7) in which a novel PSF-TFE3 fusion point was identified. All of the cases displayed TFE3 rearrangement associated with Xp11 translocation. Furthermore, we developed a PSF-TFE3 fusion fluorescence in situ hybridization assay for the detection of the PSF-TFE3 fusion gene and detected it in all 12 cases. Clinical follow-up data were available for 7 patients. Three patients died, and 2 patients (cases 1 and 3) remained alive with no evidence of disease after initial resection. Case 2 experienced recurrence and remained alive with disease. Case 5, a recent case, remained alive with extensive abdominal cavity metastases. Our data suggest that these tumors belong to a single clinicopathologic spectrum and expand the known characteristics of TFE3 rearrangement-associated tumors.

Perivascular epithelioid cell neoplasm (PEComa) of the gynecologic tract: clinicopathologic and immunohistochemical characterization of 16 cases.

Perivascular epithelioid cell tumor (PEComa) belongs to a family of tumors characterized by coexpression of melanocytic and muscle markers. Recent studies have shown that sporadic and tuberous sclerosis complex-associated PEComa may respond to mTOR inhibitors underscoring the importance of recognizing this tumor. However, its occurrence in the gynecologic tract continues to be disputed owing to its common misclassification as other types of uterine sarcoma and its controversial relationship with epithelioid smooth muscle tumors. To more fully characterize PEComa of the female genital tract, 16 cases of gynecologic PEComa were identified (1990 to 2012) and formed the basis of this study. Each case was analyzed for conventional morphologic and immunohistochemical characteristics established for PEComa of extrauterine sites; clinical outcome data were obtained for all cases. The 16 patients were aged 28 to 60 (mean 49; median 50) years, and 1 had a history of tuberous sclerosis complex. Thirteen cases were primary of the uterus, 2 of the adnexa, and 1 of the vagina. Tumor size ranged from 0.3 to 25.0 (mean 8.7) cm. Three patients died of disease, 6 were alive with disease, and 7 were alive without evidence of disease at last follow-up (1 mo to 13 y follow-up; mean 26 mo). All patients with an adverse outcome met established criteria for malignancy as proposed for extrauterine sites (ie, 2 or more features present: size ≥5 cm, high-grade nuclear features, infiltration, necrosis, lymphovascular invasion, or a mitotic rate ≥1/50 high-power fields). Of the melanocytic markers, HMB45 was most commonly expressed (16/16 positive, 100%), followed by microphthalmia transcription factor (11/12 positive, 92%), MelanA (14/16 positive, 88%), and S100 protein (2/10 positive, 20%). Of the smooth muscle markers, desmin was most commonly expressed (15/15 cases, 100%), followed by SMA (14/15 cases, 93%) and h-caldesmon (11/12 cases, 92%). TFE3 immunopositivity was identified in 5 of 13 cases; however, 3 tested cases were negative for a TFE3 rearrangement by fluorescence in situ hybridization. Current criteria for malignancy appear to be valid in the female genital tract, although modified criteria, as described herein, may be more specific. Awareness of the characteristic features of PEComa is important to help distinguish it from epithelioid smooth muscle tumors and other mimics as PEComa may respond to unique chemotherapeutic regimens.

PEComa of the gastrointestinal tract: clinicopathologic study of 35 cases with evaluation of prognostic parameters.

Perivascular epithelioid cell tumors (PEComas) are distinctive mesenchymal neoplasms that most often arise in the retroperitoneum, visceral organs, and abdominopelvic sites and usually show reactivity for melanocytic and smooth muscle markers. Fewer than 20 PEComas of the gastrointestinal (GI) tract have been reported, and behavior and criteria for malignancy are incompletely defined. The purpose of this study was to examine the clinicopathologic features of a series of GI PEComas and to evaluate prognostic parameters. A total of 35 PEComas of the GI tract were retrieved from consult and surgical files. Clinical and pathologic features were evaluated, and immunohistochemical analysis was performed. Clinical follow-up information was obtained from medical records and referring physicians. Nineteen patients were female and 16 male (median age 45 y; range, 7 to 70 y). One patient had tuberous sclerosis. Nineteen tumors arose in the colon, 12 in the small bowel, 2 in the stomach, and 1 each in gallbladder and omentum. Median tumor size was 6.2 cm (range, 0.8 to 22 cm). Three tumors were limited to the mucosa and submucosa, 8 extended to the muscularis propria, 15 to the subserosa/serosa, and 8 into the mesentery. The tumors were composed of nests and sheets of usually epithelioid cells with abundant granular eosinophilic to clear cytoplasm, surrounded by a delicate capillary vasculature. Thirteen tumors had mixed epithelioid and spindle cell components, and 2 were purely spindled. Sixteen tumors showed marked nuclear atypia. Seventeen tumors contained occasional pleomorphic cells, and 12 showed diffuse cellular pleomorphism. The median mitotic rate was 2/10 HPF (range, 0 to 36). Vascular invasion was present in 5 cases, and 16 tumors showed necrosis. By immunohistochemistry, 23/35 were positive for HMB45, 23/34 for melan-A, 15/25 for MiTF, 20/35 for smooth muscle actin, 26/35 for desmin, and 3/20 for TFE3. Focal cytoplasmic S100 protein was present in 5/27 cases, 2/25 cases were positive for KIT, and 1 case each was positive for EMA and keratin. Follow-up information was available for 31 patients (median 36 mo; range, 2 to 176 mo). Thirteen patients have developed metastases (10 liver, 3 peritoneum, 4 lymph node, 3 lung, 1 bone, 1 brain, and 1 adrenal). Thus far, 5 patients have died of disease. Metastases were significantly associated with marked atypia, diffuse pleomorphism, and mitoses ≥2/10 HPF. In summary, PEComas of the GI tract occur at similar frequency in female and male patients, most commonly involve the colon, and exhibit variable clinical behavior, ranging from benign lesions to aggressive, high-grade sarcomas. The presence of marked nuclear atypia, diffuse pleomorphism, and mitotic activity are the strongest predictors of malignant behavior.

Prognostic significance of the aggregative perivascular growth pattern of tumor cells in primary central nervous system diffuse large B-cell lymphoma.

BACKGROUND: Primary central nervous system lymphomas, predominantly diffuse large B-cell lymphomas (PCNS-DLBCL), are aggressive malignancies, and no histopathological variables with independent prognostic value are currently available. The aim of this study is to determine the prognostic value of histopathological variables of PCNS-DLBCL. METHODS: Aggregative perivascular tumor cells (APVTs) and reactive perivascular T cell infiltrates (RPVIs) in tumor samples from 62 immunocompetent patients with PCNS-DLBCL were histopathologically and immunohistochemically studied. A mouse brain DLBCL model was established to confirm the special morphological features of PCNS-DLBCL. The therapy, overall response rate (ORR), and overall survival (OS) among patients were followed up. RESULTS: APVT was present in 54 (87%) of the 62 cases, whereas RPVI was present in 20 (32%). Patients with APVT-positive lesions exhibited significantly worse OS, with intermediate to high International Extranodal Lymphoma Study Group (IELSG) scores, compared with patients with RPVI-positive lesions. Among cases of APVT-positive lymphoma, the semiquantitative score of immunostaining of X-box-binding protein (XBP1) and CD44 demonstrated prognostic significance. Multivariate analysis confirmed independent associations between APVT and XBP1 and between CD44 staining and survival. CONCLUSIONS: The presence of APVT and staining of XBP1 and CD44 are independently associated with survival among patients with PCNS-DLBCL. These features could be routinely assessed in histopathological and immunohistochemical specimens.