[Microcystic adnexal carcinoma: A case report]. / Carcinome annexiel microkystique : à propos d'une observation.

We report a case of microcystic adnexal carcinoma in a 80-year-old woman. This is a rare malignant adnexal cutaneous tumor with glandular and follicular differentiation, rare, often asymptomatic, with late diagnosis and slow growth, locally aggressive and rarely metastatic. The distinction with other benign and malignant skin tumors is difficult.

Shear Wave Elastography in Thyroid Nodules with Indeterminate Cytology: Results of a Prospective Bicentric Study.

BACKGROUND: The clinical management of thyroid nodules with indeterminate cytology (IC) remains challenging. The role of shear wave elastography (SWE) in this setting is controversial. The aim of the study was to assess the performances of SWE in terms of prediction of malignancy, reproducibility, and combined analysis with ultrasound (US) examination in thyroid nodules with IC. METHODS: This prospective study was conducted in two referral centers. Eligible patients had a thyroid nodule ≥15 mm with IC (Bethesda class III-V) for which surgery had been recommended. Patients underwent a standardized US evaluation combined with a SWE exam followed by surgery. SWE parameters included mean (meanEI; kPa) and max (maxEI) elasticity values, and ratio (meanEI nodule/parenchyma). RESULTS: One hundred and thirty-one nodules (median size 30 mm) in 131 patients were studied. IC was class III in 28%, class IV in 64%, and class V in 8% of cases. After surgery, 21 (16%) nodules were malignant, including nine papillary thyroid cancers (PTC), six follicular thyroid cancers, five poorly differentiated carcinomas, and one large B-cell lymphoma. SWE parameters were similar in benign and malignant nodules, including meanEI (20.2 vs. 19.6 kPa), maxEI (34.3 vs. 32.5 kPa), and ratio (1.57 vs. 1.38). In malignant nodules, meanEI, maxEI, and ratio were higher in the classic PTC variants (n = 4) than in the other PTC variants (n = 5; p < 0.02) and in non-PTC tumors (n = 12; p < 0.005). Intra- and inter-observer coefficients of variations for meanEI in nodules were 23% and 26%, respectively. The French Thyroid Imaging Reporting and Data System score, the American Thyroid Association US classification, and the EU-Thyroid Imaging Reporting and Data System were not associated with malignancy. CONCLUSIONS: Despite high elasticity values in classic PTC variants, conventional SWE indexes failed to discriminate between benign and malignant tumors in thyroid nodules with IC.

Molecular Pathology of Anaplastic Thyroid Carcinomas: A Retrospective Study of 144 Cases.

BACKGROUND: Anaplastic thyroid carcinoma (ATC) is a rare tumor, with poorly defined oncogenic molecular mechanisms and limited therapeutic options contributing to its poor prognosis. The aims of this retrospective study were to determine the frequency of anaplastic lymphoma kinase (ALK) translocations and to identify the mutational profile of ATC including TERT promoter mutations. METHODS AND MATERIALS: One hundred and forty-four ATC cases were collected from 10 centers that are a part of the national French network for management of refractory thyroid tumors. Fluorescence in situ hybridization analysis for ALK rearrangement was performed on tissue microarrays. A panel of 50 genes using next-generation sequencing and TERT promoter mutations using Sanger sequencing were also screened. RESULTS: Fluorescence in situ hybridization was interpretable for 90 (62.5%) cases. One (1.1%) case was positive for an ALK rearrangement with a borderline threshold (15% positive cells). Next-generation sequencing results were interpretable for 94 (65.3%) cases, and Sanger sequencing (TERT) for 98 (68.1%) cases. A total of 210 mutations (intronic and exonic) were identified. TP53 alterations were the most frequent (54.4%). Forty-three percent harbored a mutation in the (H-K-N)RAS genes, 13.8% a mutation in the BRAF gene (essentially p.V600E), 17% a PI3K-AKT pathway mutation, 6.4% both RAS and PI3K pathway mutations, and 4.3% both TP53 and PTEN mutations. Nearly 10% of the cases showed no mutations of the RAS, PI3K-AKT pathways, or TP53, with mutations of ALK, ATM, APC, CDKN2A, ERBB2, RET, or SMAD4, including mutations not yet described in thyroid tumors. Genes encoding potentially druggable targets included: mutations in the ATM gene in four (4.3%) cases, in ERBB2 in one (1.1%) case, in MET in one (1.1%) case, and in ALK in one (1.1%) case. A TERT promoter alteration was found in 53 (54.0%) cases, including 43 C228T and 10 C250T mutations. Three out of our cases did not harbor mutations in the panel of genes with therapeutic interest. CONCLUSION: This study confirms that ALK rearrangements in ATC are rare and that the mutational landscape of ATC is heterogeneous, with many genes implicated in the follicular epithelial cell dedifferentiation process. This may explain the limited effectiveness of targeted therapeutic options tested so far.

Incremental Value of a Dedicated Head and Neck Acquisition during 18F-FDG PET/CT in Patients with Differentiated Thyroid Cancer.

OBJECTIVES: 18F-FDG-PET/CT is a useful tool used to evidence persistent/recurrent disease (PRD) in patients with differentiated thyroid cancer and iodine-refractory lesions. The aim of this study was to compare the diagnostic value at the cervical level of the routine whole-body (WB) acquisition and that of a complementary head and neck (HN) acquisition, performed successively during the same PET/CT study. METHODS: PET/CT studies combining WB and HN acquisitions performed in 85 consecutive patients were retrospectively reviewed by two nuclear medicine physicians. 18F-FDG uptake in cervical lymph nodes (LN) or in the thyroid bed was assessed. Among the 85 patients, the PET/CT results of the 26 who subsequently underwent neck surgery were compared with surgical and pathological reports. The size of each largest nodal metastasis was assessed by a pathologist. RESULTS: In the 85 patients, inter-observer agreement was excellent for both WB and HN PET/CT interpretation. Of the 26 patients who underwent surgery, 25 had pathology proven PRD in the neck. Of these 25 patients, 15 displayed FDG uptake on either WB or HN PET. In these 15 patients, HN PET detected more malignant lesions than WB PET did (21/27 = 78% vs. 12/27 = 44%, P = 0.006). Node/background ratios were significantly higher on HN than on WB PET (P<0.0001). Three false-negative studies (20%) on WB PET were upstaged as true-positive on HN PET. The mean size of the largest LN metastasis was 3 mm for the LN detected neither on WB nor on HN PET, 7 mm for the metastasis detected on HN but not on WB PET, and 13 mm for those detected on both acquisitions (P = 0.0004). Receiver-Operating Characteristic analysis showed that area under the curve was higher for HN PET than for WB PET (0.97 [95%CI, 0.90-0.99] vs 0.88 [95%CI, 0.78-0.95], P = 0.009). CONCLUSIONS: HN acquisition improves the ability to detect PRD in the neck compared with WB acquisition alone. We recommend systematically adding an HN acquisition when PET/CT is performed to detect PRD in the neck.

[Vaginal adenosis: A case report and literature review]. / Adénose vaginale : à propos d'une observation et revue de la littérature.

We report a case of vaginal adenosis in a woman of 42years. This is a rare congenital disorder since cessation of use of diethylstilbestrol (DES), usually of benign course, not to ignore in its tubo-endometrial histological form which may progress to atypical adenosis precursor of vaginal clear cell adenocarcinoma in patients exposed in utero to DES.

Identification of I1171N resistance mutation in ALK-positive non-small-cell lung cancer tumor sample and circulating tumor DNA.

Anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC) is sensitive to ALK inhibitor therapy, but resistance invariably develops and can be mediated by certain secondary mutations. The detection of these mutations is useful to guide treatment decisions, but tumors are not always easily accessible to re-biopsy. We report the case of a patient with ALK-rearranged NSCLC who presented acquired resistance to crizotinib and then alectinib. Sequencing analyses of DNA from a liver metastasis biopsy sample and circulating tumor DNA both found the same I1171N ALK kinase domain mutation, known to confer resistance to certain ALK inhibitors. However, the patient then received ceritinib, a 2nd generation ALK inhibitor, and achieved another partial response. This case underlines how ALK resistance mutation detection in peripheral blood could be a reliable, safer, and less invasive alternative to tissue-based samples in NSCLC.

Prognostic value of microscopic lymph node involvement in patients with papillary thyroid cancer.

CONTEXT: The impact of microscopic nodal involvement on the risk of persistent/recurrent disease (PRD) remains controversial in patients with papillary thyroid carcinoma (PTC). OBJECTIVE: The goal of the study was to assess the risk of PRD and the 4-year outcome in PTC patients according to their initial nodal status [pNx, pN0, pN1 microscopic (cN0/pN1) or pN1 macroscopic (cN1/pN1)]. DESIGN: We conducted a retrospective cohort study. PATIENTS: The study included 305 consecutive PTC patients referred for radioiodine ablation from 2006 to 2011. MAIN OUTCOME MEASURE: We evaluated the risk of structural PRD and the disease status at the last follow-up. At ablation, persistent disease was consistently assessed by using post-radioiodine ablation scintigraphy combining total body scan and neck and thorax single-photon computed tomography-computed tomography (SPECT-CT) acquisition. RESULTS: Of 305 patients, 128 (42%) were pNx, 84 (28%) pN0, 44 (14%) pN1 microscopic, and 49 (16%) pN1 macroscopic. The 4-year cumulative risk of PRD was higher in pN1 macroscopic than in pN1 microscopic patients (49% vs 24%, P = .03), and higher in pN1 microscopic than in pN0 (12%, P = .01) or pNx patients (6%, P < .001). On multivariate analysis, tumor size of 20 mm or greater [relative risk (RR) 3.4; P = .0001], extrathyroid extension (RR 2.6; P < .003), pN1 macroscopic (RR 4.5; P < .0001), and pN1 microscopic (RR 2.5; P < .02) were independent risk factors for PRD. At the last visit, the proportion of patients with no evidence of disease decreased from pNx (98%), pN0 (93%), and pN1 microscopic (89%) to pN1 macroscopic patients (70%) (P < .0001, Cochran-Armitage trend test). Extrathyroid extension (odds ratio 9.7; P < .0001) and N1 macroscopic (OR 4.9; P < .001) independently predicted persistent disease at the last visit, but N1 microscopic did not. CONCLUSIONS: PATIENTS with microscopic lymph node involvement present an intermediate outcome between that observed in pN0-pNx patients and pN1 macroscopic patients. These data may justify modifications to the risk recurrence staging systems.

Prognostic factors and impact of adjuvant treatments on local and metastatic relapse of soft-tissue sarcoma patients in the competing risks setting.

BACKGROUND: In the medical literature many analyses of outcomes of sarcoma patients were performed without regard to the problem of "competing risks." METHODS: We analyzed local relapse-free and metastasis-free survival in a population of 3255 adult patients with a primary soft-tissue sarcoma (STS) included in the French Sarcoma Group database. Cumulative incidence of local and metastatic relapse was estimated by accounting for death as a competing event. RESULTS: On multivariate analysis, age, tumor site, histological subtype, and grade were independent adverse prognostic factors for local relapse, whereas tumor depth and size had no influence. Histological subtype, tumor depth, tumor size, and grade were independent adverse prognostic factors for metastatic relapse. Despite a higher incidence of competing deaths in patients managed with adjuvant radiotherapy than in patients not receiving radiotherapy, adjuvant radiotherapy was associated with a significant benefit in terms of local relapse-free survival. Despite a similar cumulative incidence of competing deaths in patients with grade 2 and grade 3 disease, we found that the benefit of adjuvant chemotherapy was present only in patients with grade 3 and not in patients with grade 2 disease. CONCLUSIONS: In the setting of competing risks, tumor biology reflected by histological grade is a crucial predictor of local relapse, whereas tumor depth and size have poor if any influence. Grade could also predict the benefit of adjuvant chemotherapy in patients with STS.

Long-term recurrence of soft tissue sarcomas: prognostic factors and implications for prolonged follow-up.

BACKGROUND: To the authors' knowledge, the incidence of late recurrence (> 5 years after initial management) is unknown and no prognostic factors for late events have been characterized in patients with soft tissue sarcomas. METHODS: Follow-up data from patients with localized soft tissue sarcoma who were included in the French Sarcoma Group database from January 1990 to June 2005 were reviewed. The outcomes of interest were the cumulative probabilities of late (> 5 years) local and metastatic disease recurrence with death as a competing event. Estimations and 95% confidence intervals (95% CIs) were computed with the cumulative incidence function. RESULTS: A total of 719 patients who were alive and event free > 5 years after their initial diagnosis were included in the current study. Sixty-seven patients (9.3%) developed a late local recurrence and 42 patients (5.8%) developed a late metastatic recurrence, respectively. On multivariate analysis, internal trunk location (hazard ratio [HR], 3.9; 95% CI, 2.2-6.7 [P < .001]) and tumor size > 100 mm (HR, 2.1; 95% CI, 1.1-4 [P = .035]) were the 2 factors found to be independently associated with an increased risk of late local recurrence. Grade > 1 (graded according to the French Federation of Cancer Centers Sarcoma Group) (HR, 4.7; 95% CI 1.1-21 [P = .04]) was the sole factor found to be independently associated with an increased risk of late metastatic recurrence. CONCLUSIONS: Late recurrence of soft tissue sarcoma is relatively uncommon. However, the results of the current study emphasize the critical role of long-term follow-up to detect late local disease recurrence in patients with retroperitoneal or very large soft tissue sarcomas, and late metastatic recurrence in patients with high-grade disease. Conversely, the prolonged follow-up of patients with grade 1 disease is not needed.

Malignant pilomatricoma: two new observations and review of the relevant literature.

Malignant pilomatricoma or pilomatrical carcinoma is a rare malignant hair follicle neoplasm. This tumor is locally aggressive with increased tendency to recur, but a low metastatic potential. Its histopathological diagnosis is difficult and based on a detailed evaluation of the infiltrative nature, the importance of the mummified and necrotic cell component, atypical mitoses, and perineural or vascular invasion. Surgical wide resection is the recommended treatment. It reduces the risk of focal recurrence by 50%. Here we report two new cases including one that occurred on a lesion initially diagnosed as benign pilomatricoma.

[Treatment of primary thyroid lymphomas]. / Traitement des lymphomes thyroïdiens primitifs de stade localisé

Primary lymphomas of the thyroid (LPT) are a rare entity. LPT represent between 5 and 15% of all thyroid neoplasms. Cytology has limited value; biopsy should be recommended. The differential diagnosis of thyroid carcinoma is differentiated forms indolent or aggressive forms for anaplastic and high grade that may occur by a mass rapidly progressive and compressive. LPT represent a histologically and clinically heterogeneous disease. The most common forms are high-grade LPT (DBLCL) of diffuse large cell type or mucosa-associated lymphoid tissue (MALT). DBLCL receive chemotherapy. The benefit of irradiation is highly debated in view of the data from randomized lymphoma studies (nodal with a minority of extranodal forms) versus those of retrospective studies specifically addressing the case of LPT. Localized MALT lymphomas can be treated with radiation alone. The treatment of other LPT is presented.

Genetic profiling identifies two classes of soft-tissue leiomyosarcomas with distinct clinical characteristics.

PURPOSE: Data about the prognostic factors of soft-tissue leiomyosarcomas and their correlation with molecular profile are limited. EXPERIMENTAL DESIGN: From 1990 to 2010, 586 adult patients with a primary soft-tissue leiomyosarcoma were included in the French Sarcoma Group (GSF) database after surgery of the primary tumor. Multivariate analyses were conducted by Cox regression model in a backward stepwise procedure. Genetic profiling was conducted for 73 cases. RESULTS: Median age was 59 years (range, 21-98 years). The median follow-up of patients alive was 46 months. The 5-year metastasis-free survival (MFS) rate was 51% (95% location and grade > I were independent adverse prognostic factors for MFS). The 5-year overall survival (OS) rate was 63% [95% confidence interval (CI), 59-67]. On multivariate analysis, age ≥ 60 years old, tumor size > 5 cm, deep location, and grade > I were independent adverse prognostic factors for OS. Molecular profiling identified specific clusters with activation of different biologic pathways: retroperitoneal leiomyosarcomas are characterized by overexpression of genes involved in muscle differentiation and nonretroperitoneal leiomyosarcomas characterized by overexpression of genes mainly involved in extracellular matrix, wounding, and adhesion pathways. The CINSARC signature but not comparative genomic hybridization (CGH) profiling was predictive of outcome. CONCLUSION: Soft-tissue leiomyosarcomas represent a heterogeneous group of tumors with at least two categories, retroperitoneal and extremities leiomyosarcomas, having specific clinical outcome and molecular features. Future clinical trials should consider this heterogeneity for a better stratification of patients.

Localised angiosarcomas: the identification of prognostic factors and analysis of treatment impact. A retrospective analysis from the French Sarcoma Group (GSF/GETO).

BACKGROUND: Angiosarcomas represent less than 2% of all adult soft tissue sarcomas. Prognostic factors and the role of (neo-) adjuvant treatments in the management of localised angiosarcomas require further investigation. METHODS: We have conducted a retrospective multicenter study (June 1980 to October 2009) of 107 patients with localised angiosarcomas. All of the cases were centrally reviewed by a certified pathologist. Univariate and multivariate analyses were conducted to identify independent poor prognostic factors (PF). Overall survival (OS) and Local Recurrence-Free Survival (LRFS) were estimated using the Kaplan-Meier method. The effect of treatments was explored using the Cox model after adjusting for the PF. RESULTS: The median age was 71 years. 22.4% and 62.6% developed an angiosarcoma in pre-existing lymphoedema and within irradiated tissue respectively. The median OS, LRFS and Disease Recurrence-Free Survival (DRFS) were 38.8, 27 and 36.1 months, respectively. In multivariate analysis, the following parameters influenced the OS: lymphoedema (Hazard ratio (HR)=2.0) and size >5cm (HR=1.5). After adjustment to these PF, R0 margins was the only treatment parameter that improving the OS (HR=0.2). In the multivariate analysis, the LRFS was influenced by an age >70 (HR=1.8) and pre-existing lymphoedema (HR=2.0). After adjustment for these PF, R0 margins (HR=0.5) and adjuvant radiotherapy (HR=0.3) improved the LRFS. CONCLUSIONS: Our results suggest the following points: (i) pre-existing lymphoedema, tumour size and age >70 are probably the major prognostic factors in patients with localised angiosarcomas; (ii) the achievement of R0 margins is probably of major importance for improving the patient outcome and (iii) adjuvant radiotherapy probably decreased the risk of local recurrence.