Evaluation of pathology review at gynaecological oncology multidisciplinary team meetings: a 5-year prospective analysis of cases with major diagnostic discordance.

Multidisciplinary team meetings (MDTs) play an essential role in the management of patients with newly diagnosed and recurrent cancers, and often include review of pathology specimens that were initially assessed in external departments. Many studies have demonstrated a low but significant rate of diagnostic disagreement following such review but the pathological findings have seldom been detailed. We present a prospective 5-year study of all external cases reviewed at the Western Australian Gynaecological Oncology MDT focusing upon those cases with major diagnostic discordance likely to impact patient management. In total, 1275 cases were reviewed of which 132 (10.4%) were considered discordant including 48 (3.8%) with major discordance. Different interpretation of the presence and/or extent of tumour invasion accounted for a significant proportion of cases and in particular some adenocarcinoma and squamous carcinoma variants were initially reported to show only in situ or minimally invasive disease. Endometrial high-grade serous carcinoma was under-recognised and on occasion reassignment of tumour origin including metastasis to the gynaecological tract was facilitated by additional clinical information and supported by appropriate immunohistochemistry. This study supports the role of pathology review at MDTs and highlights problematic lesions that may merit a low threshold for additional opinion and ancillary studies.

Extravascular Migratory Metastasis (Pericytic Mimicry) in Sarcomatoid Squamous Cell Carcinoma of the Vulva: A Report of 2 Cases.

Extravascular migratory metastasis (EVMM), also known as pericytic mimicry or angiotropism, is a mechanism of angiocentric tumor spread that has been investigated mainly in cutaneous malignant melanoma where it has been associated with an increased risk of metastasis. In EVMM, the tumor cells spread along the external (ablumenal) aspect of vessels without breaching the endothelium, a process that is therefore distinct from the more widely recognized intraluminal invasion. Although EVMM has also been reported in a limited range of other tumor types, to our knowledge it has not been described in squamous cell carcinoma (SCC). Herein we report EVMM in 2 cases of sarcomatoid SCC of the vulva. The tumors arose in patients aged 78 and 61 yr both of whom had previous histories of histologically conventional vulval SCCs occurring in a background of lichen sclerosus and differentiated-type vulval intraepithelial neoplasia. Both tumors recurred leading to fatal metastasis in 1 patient and a requirement for pelvic exenteration in the second. Intravascular tumor involvement was not identified in either case. These cases support the view that sarcomatoid SCCs of the vulva are clinically aggressive neoplasms, and EVMM may contribute toward the risk of local and distant spread in these tumors.

Prognostic Role of Histological Tumor Regression in Patients Receiving Neoadjuvant Chemotherapy for High-Grade Serous Tubo-ovarian Carcinoma.

OBJECTIVE: Our objective was to validate the prognostic role of the chemotherapy response score (CRS), which has been proposed for measuring tumor response to neoadjuvant chemotherapy in patients with high-grade serous tubo-ovarian carcinoma, in predicting progression-free survival (PFS) and overall survival (OS). METHODS: A retrospective cohort study was conducted of patients with advanced high-grade serous tubo-ovarian carcinoma diagnosed between January 1, 2010, and December 31, 2014, and treated with neoadjuvant chemotherapy. Treatment-related tumor regression was determined according to the 3-tier CRS, and results were compared with standard clinicopathological variables. Survival analysis was performed using Cox proportional hazards models and the log-rank test. RESULTS: Seventy-one patients were eligible for analysis. Median OS was 25.5 months. Fifty-eight patients (82%) had disease recurrence and 32 (45%) had died at study census. Of the 71 patients, 19, 29, and 23 patients had a CRS of 1, 2, and 3, respectively. On univariate analysis, the CRS significantly predicted PFS (hazard ratio [HR], 3.77; 95% confidence interval [CI], 1.83-7.78; P = 0.000) and OS (HR, 2.81; 95% CI, 1.16-6.79; P = 0.022). In a multivariate model, the CRS was significantly associated with PFS (HR, 2.81; 95% CI, 1.16-6.79; P = 0.022) but not with OS (HR, 2.39; 95% CI, 0.47-3.08; P = 0.079). Patients with CRS of 1 and 2 combined were twice as likely to progress during the study period compared with patients with a CRS of 3 (HR, 2.0; 95% CI, 1.06-3.78; P = 0.032; median PFS, 16 vs 26 months). No significant association was observed for OS (CRS 1/2 vs 3; HR, 1.57; 95% CI, 0.68-3.65; P = 0.291). CONCLUSIONS: In this study, the CRS showed independent prognostic significance for PFS but not for OS.

Gastrointestinal stromal tumours (GISTs): a clinicopathological and molecular study of 66 cases.

AIMS: Predicting the clinical behaviour of gastrointestinal stromal tumours (GISTs) is difficult and criteria delineating benign from malignant cases are not firmly established. The aims of this study were to define the clinicopathological and molecular features of 66 GISTs, and to determine whether any specific parameters were associated with patient outcome. METHODS: Archival cases of GIST from two major teaching hospitals in Western Australia were studied. Inclusion criteria for the study were: (1) appropriate morphology, (2) CD117 positivity, (3) adequacy of pathological material for study, and (4) exclusion of other tumour types on the basis of immunophenotypic and/or ultrastructural features. Expression of CD117, CD34, S100 protein, keratin (using broad spectrum MNF116), alpha-smooth muscle actin (SMA) was determined by immunohistochemistry. PCR and single strand conformation polymorphism (PCR-SSCP) analysis were used to screen for mutations in exons 11 and 9 of c-kit. RESULTS: There were equal numbers of males and females with a mean age at diagnosis of 60 years, followed up for a mean of 54 months. Thirteen patients (21%) had died of GIST by the end of the study. Tumours were mostly located in the stomach (67%) and small intestine (SI; 25%). The cell types were pure spindle (68%), pure epithelioid (12%) and mixed epithelioid/spindle (20%). c-kit mutations were found in 69% of GISTs, with the large majority (91%) occurring in exon 11. Size > or = 10 cm, tumour necrosis and pure epithelioid cell morphology each were the only factors significantly associated with adverse survival (p=0.038, and p=0.047 and p=0.028, respectively). Mitotic activity > or = 5/50 HPF showed a definite trend association with adverse survival, but unlike some other studies, did not achieve statistical significance (p=0.067). c-kit mutations were more frequent in small intestinal GISTs (p=0.05) and in those with pure spindle cell morphology (p=0.023) but were not associated with patient outcome. CONCLUSION: In this study, size > or = 10cm, necrosis and/or pure epithelioid cell morphology correlated significantly with adverse survival. Mitotic activity showed a strong association with survival but this did not reach statistical significance. c-kit mutations occurred mainly in GISTs of the SI, and in purely spindle cell tumours. While the mutation status did not associate with patient outcome in this series, this remains a controversial issue, and further studies are needed to assess whether the type of mutation affects response to tyrosine kinase inhibitor therapy in metastatic GISTs. CD117 staining of any mesenchymal lesion of the gastrointestinal tract should be mandatory for accurate classification. PCR-SSCP analysis is a fast, sensitive and relatively inexpensive method of analysing c-kit mutations, which may be important prognostically and also of therapeutic relevance in the assessment of new tyrosine kinase inhibitor therapies.