Metastatic non clear cell renal cell carcinoma (nccRCC) is an heterogenous group, usually excluded from phase 3 trials. We report real life data of prognosis and systemic management of those patients.
We retrospectively included 102 metastatic nccRCC patients (unspecified papillary, n = 10; type 1 and 2 papillary n = 10 and n = 32; translocation RCC, n = 9; chromophobe, n = 14; collecting duct, n = 14) treated between 2006 and 2020. Objective response rate (ORR), progression-free survival (PFS) and overall survival (OS) were evaluated.
Among patients who underwent pathological review, 40.8% presented a complete histological discordance. First line treatments were mainly tyrosine kinase inhibitor (60.8%), combination including immunotherapy (7.8%) or combination of chemotherapy (13.7%). Median ORR ranged from 0% in unspecified papillary RCC to 42.9% in type 1 papillary RCC. Median PFS ranged from 2.9 months in collecting duct carcinoma to 10.9 months in type 1 papillary RCC. Median OS ranged from 6.8 months in collecting duct carcinoma to 29.1 months in MiT family translocation RCC. Thirty (29.4%) patients were included in a treatment trial during their treatment course.
Metastatic nccRCC patients have variable prognosis due to heterogeneity of histological subtypes. Their diagnosis and access to therapeutic innovation remain suboptimal. Dedicated prospective trials are needed.

Since 2010, the network of rare malignant tumors of the ovary (TMRG) was developed to optimize the management of patients, also allowing a histological second opinion of rare ovarian tumors. The aim of this work was to study the contribution of second opinion to improve histological diagnostic accuracy on ovarian rare malignant tumors included in the TMRG database.
Histological data of patients diagnosed with a rare ovarian tumor included in TMRG network over a one-year period (2018) were collected. Initial diagnoses were compared with second opinion from national gynecological pathologist experts. The modalities of histological second opinion requests were studied, as well as the histological characteristics of the tumors. The discordances were classified as minor (if the modification of histological diagnosis did not change patient management) and major (if the patient management can be modified).
Of 1185 included patients, 937 matched the inclusion criteria. Full concordance between primary diagnosis and expert second opinion was reached in 611 cases (65,3%), minor discordance was seen in 114 (12,2%) and major discordance in 209 (22,3%) of cases. In systematic review requested by the network, 26% (n = 137) of cases were reported with a change in histological diagnosis, while the change concerned 44% (n = 186) of cases for a second opinion spontaneously requested by the initial pathologist. The discrepancies concerned all categories of ovarian tumors, with a majority of mucinous tumors (43% of major discordances), followed by stromal and sex-cord tumors (13.8% of major discordances) and clear cell tumors (12,4% of major discordances).
This analysis confirms the diagnostic difficulty of ovarian tumors, due to their rarity and morphological heterogeneity. French pathologists are aware of these difficulties and spontaneously refer ovarian tumors with unusual histology for a second opinion and collaborate with rare tumor networks for systematic review.

To determine the accuracy of uterine corpus invasion (UCI) diagnosis in patients with cervical cancer and identity risk factors for UCI and depth of invasion.
Clinical data of patients with cervical cancer who underwent hysterectomy between 2004 and 2016 were retrospectively reviewed. UCI was assessed on uterine pathology. Independent risk factors for UCI and depth of invasion were identified using binary and ordinal logistic regression models, respectively.
A total of 2,212 patients with cervical cancer from 11 medical institutions in China were included in this study. Of these, 497 patients had cervical cancer and UCI, and 1,715 patients had cervical cancer and no UCI, according to the original pathology reports. Retrospective review of the original pathology reports revealed a missed diagnosis of UCI in 54 (10.5%) patients and a misdiagnosis in 36 (2.1%) patients. Therefore, 515 patients with cervical cancer and UCI (160 patients with endometrial invasion, 176 patients with myometrial invasion < 50%, and 179 patients with myometrial invasion ≥ 50%), and 1697 patients with cervical cancer without UCI were included in the analysis. Older age, advanced stage, tumor size, adenocarcinoma, parametrial involvement, resection margin involvement, and lymph node metastasis were independent risk factors for UCI. These risk factors, except resection margin involvement, were independently associated with depth of UCI.
UCI may be missed or misdiagnosed in patients with cervical cancer on postoperative pathological examination. Older age, advanced stage, tumor size, adenocarcinoma, parametrial involvement, resection margin involvement, and lymph node metastasis were independent risk factors for UCI and depth of UCI, with the exception of resection margin involvement.

To determine the associations between the presence and depth of uterine corpus invasion and survival in patients with cervical cancer.
Clinical data of patients with stage IA2-IIB cervical cancer who underwent radical hysterectomy between 2004 and 2016 were retrospectively reviewed. Uterine corpus invasion was identified from a review of uterine pathology. Independent prognostic factors for 5-year disease-free survival (DFS) and overall survival (OS) were identified using multivariate forward stepwise Cox proportional hazards regression models.
A total of 1414 patients with stage IA2-IIB cervical cancer from 11 medical institutions in China were included. Retrospective review of the original pathology reports revealed a missed diagnosis of uterine corpus invasion in 38 (13.4%) patients and a misdiagnosis in 20 (1.8%) patients. Therefore, 284 patients with cervical cancer and uterine corpus invasion (90 [31.7%] patients had endometrial invasion, 105 [37.0%] patients had myometrial invasion <50%, and 89 [31.3%] patients had myometrial invasion ≥50%), and 1130 patients with cervical cancer without uterine corpus invasion were included in the analysis. The 5-year DFS and OS were significantly shorter for patients with uterine corpus invasion compared to patients with no uterine corpus invasion. Myometrial invasion ≥50% was an independent prognostic factor associated with decreased 5-year DFS (aHR, 2.307, 95% CI, 1.588-3.351) and 5-year OS (aHR, 2.736, 95% CI, 1.813-4.130), while myometrial invasion <50% or endometrial invasion had no effect on patient outcomes.
Diagnosis of uterine corpus invasion is frequently missed. Myometrial invasion ≥50% within the uterine corpus was an independent factor associated with worse prognosis in patients with cervical cancer, while myometrial invasion <50% or endometrial invasion had no effect on outcomes.

BACKGROUND: Malignant granular cell tumors (MGCTs) are extremely rare neoplasms with only a limited number of studies published to date. The aim of this study is to elucidate the clinicopathological characteristics and prognostic factors of MGCTs.
METHODS: This is a multi-institutional retrospective study of MGCTs with a central pathological review. A total of 18 cases were retrieved. Specimens were blindly reviewed by two pathologists based on the diagnostic criteria by Fanburg-Smith et al. Kaplan-Meier survival probabilities were calculated, and risk factors for poor prognosis were evaluated.
RESULTS: Three and fifteen cases were diagnosed as atypical GCTs (AGCTs) and mGCTs according to the Fanburg-Smith et al. classification, respectively. Four (one atypical and three malignant) cases had metastasis at the first presentation, including lymph node metastasis. Three out of ten cases treated with wide resection developed local recurrence. Although prolonged static disease periods of ≥1 year were observed in four cases receiving chemotherapy, all cases with local recurrence or metastasis, including two atypical cases, eventually died of disease. The 5- and 10-year overall survival rates for localized MGCTs were 69.2 and 34.6 %, respectively. The presence of necrosis was revealed as a risk factor associated with adverse clinical outcomes.
CONCLUSIONS: MGCTs have high rates of recurrence and metastasis including lymph node metastasis. As histologically atypical cases also have metastatic potential, close attention should be paid to AGCTs. The combination of histological evaluation and tumor size may lead to more accurate diagnosis of this rare neoplasm.

TENpath is a network for the expert pathological diagnosis of malignant neuroendocrine tumors of the adult, both familial and sporadic, created by the French National Institute of Cancer in 2010. After 3years of activity, a first evaluation can be made. The perimeter of the network includes all neuroendocrine tumors (except small cell carcinomas of the lung), medullary carcinomas of the thyroid and extra-adrenal paragangliomas. The objectives of the network are not only the pathological review of all newly diagnosed cases of neuroendocrine tumors, but also the epidemiological surveillance, the training of pathologists, the production of recommendations and the initiation of research projects. The organisation of the network includes a database in which all referred cases are declared and a virtual expert system making it possible collegial expertises in line. Twenty-two expert centers are currently participating to TENpath. A total of 1350 cases have been referred in 2011 and 1518 in 2012. Major discrepancies amounted up to 5.9% in 2011 and to 2.9% in 2012. They mainly involved problems of differential diagnosis and wrong evaluations of the differentiation status of the tumor. The lessons to draw from the first years of TENpath are: (a) the long-standing underestimation of the actual number of patients with neuroendocrine tumors in France, (b) a better delineation, based on objective data, of the cases raising actual problems of diagnosis, (c) the existence of cases raising problems of classification even to experts and justifying a particular effort of research. These informations will be important to discuss the future evolution of TENpath.