Reproducibility in PD-L1 Immunohistochemistry Quantification through the Tumor Proportion Score and the Combined Positive Score: Could Dual Immunostaining Help Pathologists?

We studied the pathologists' agreements in quantifying PD-L1 expression through the tumor proportion score (TPS) and the combined positive score (CPS) using single PD-L1 immunohistochemistry (S-IHC) and double immunohistochemistry (D-IHC) combining PD-L1 staining and tumor cell markers. S-IHC and D-IHC were applied to 15 cancer samples to generate 60 digital IHC slides (30 whole slides images and 30 regions of interest of 1 mm2) for PD-L1 expression quantification using both TPS and CPS, twice by four pathologists. Agreements were estimated calculating intraclass correlation coefficients (ICC). Both S-IHC and D-IHC slides analyses resulted in excellent (for TPS, ICC > 0.9) to good (for CPS, ICC > 0.75) inter- and intra-pathologist agreements with slightly higher ICC with D-IHC than with S-IHC. S-IHC resulted in higher TPS and CPS than D-IHC (+5.6 and +6.1 mean differences, respectively). High reproducibility in the quantification of PD-L1 expression is attainable using S-IHC and D-IHC.

An exceptional case of degenerative endometriosis of the uterine torus.

There are less than ten cases of deep endometriosis degeneration in the literature. The duration of endometriosis, the ovarian stimulation, the perimenopause and the obesity exposes the woman to an increased risk of endometriosis degeneration.

Incidental Finding of a Tongue Schwannoma Mimicking Local Recurrence of Squamous Cell Carcinoma on a Systematic Follow-up 18F-FDG PET/CT.

ABSTRACT: Schwannomas are usually benign, rare, and slow-growing nerve sheath tumor composed of Schwann cells. They develop in the head and neck area in approximately 25% to 40% of cases, of which 1% in the oral cavity, where the tongue remains the preferred site. Malignant transformation occurs in approximately 8% to 10% cases. We report a unique case of a histologically proven FDG-avid schwannoma of the left mobile portion of the tongue, showing an 18F-FDG avidity on PET/CT, which was a false-positive result for local recurrence in a patient followed for squamous cell carcinoma.

PD-L1 expression in recurrent head and neck squamous cell carcinoma.

PURPOSE: To evaluate the Programmed Cell Death Ligand (PD-L1) expression at diagnosis and relapse in patients with head and neck carcinoma (HNSCC) treated with radio(chemo)therapy. METHODS: PD-L1 immunohistochemistry was performed in tumor cells (TC) and immune cells (IC) in 44 patients and scored as 0 = 0%, 1 = < 5%, 2 = 6-49% or 3 = ≥ 50% cells. RESULTS: PD-L1 expression on TC before RT was scored as 0, 1, 2 and 3 in 28, 4, 8 and 4 patients, respectively. In 10 patients, IC did not show any PD-L1 expression; while in 8, 16, and 10 patients, PD-L1 expression was scored 1, 2 and 3, respectively. At relapse, 7/36 patients had a PD-L1 expression positivation in TC, while the opposite was observed in 6 patients. Overall, survival at 2 years was higher in patients with PD-L1 expression (90% versus 62.5%, p = 0.032). CONCLUSION: PD-L1 expression may vary throughout the course of the disease. A re-evaluation of PD-L1 expression on biopsies at the time of recurrence should be recommended.

Laparoscopy-assisted immediate vaginal reconstruction with a vertical pedicled deep inferior epigastric perforator flap for primary melanoma of the vagina.

The vagina is a rare site for primary melanoma. Here, we report on a case of laparoscopy-assisted immediate vaginal reconstruction with vertical pedicled deep inferior epigastric perforator flap.

Xanthogranulomatous endometritis: A case report and literature review.

Xanthogranulomatous endometritis is a rare benign pathology mimicking endometrial carcinoma.

Breast cancer tumor heterogeneity has only little impact on the estimation of the Oncotype DX® recurrence score using Magee Equations and Magee Decision Algorithm™.

Oncotype DX® assay is used to guide therapeutic decisions in early-stage invasive breast carcinoma but remains expensive. Magee Equations (MEs) and Magee Decision Algorithm (MDA) predict the Oncotype DX® recurrence score (RS) on the basis of histopathological parameters. The influence of intratumor heterogeneity on MEs and MDA remains uncertain. We compared Ki-67, estrogen and progesterone receptors, and human erb-b2 receptor tyrosine kinase 2 (HER2) status on tissue microarray cores with the corresponding findings on the whole slides to calculate MEs scores and to decide if Oncotype DX® testing was required as per MDA in two sets of 175 and 59 tumors, without and with Oncotype DX® results, respectively. Agreements in the interpretation of Ki-67, estrogen and progesterone receptors, and HER2 status were very good between limited areas and whole-slide analyses. This resulted also in very good agreements about the results of MEs and MDA. For 7 of 175 (4%) and 3 of 59 (5.1%) cases, MEs and MDA results in different tumor areas would have changed the indication to perform or not perform Oncotype DX® assays. Oncotype DX® RSs were significantly correlated with MEs and MDA results, but among cases initially predicted to have an RS ≤25 using MDA, 3 of 34 cases (8.8%) had in fact an RS >25. Tumor heterogeneity appears to have little impact on the estimation of the Oncotype DX® RS using MEs and MDA and would have permitted to avoid half of Oncotype DX® assays in our series. Caution is nevertheless required in discarding Oncotype DX® assay in cases with ME scores >18 associated with low mitotic activity.

EPR17341 and A7H6R pan-TRK Immunohistochemistry Result in Highly Different Staining Patterns in a Series of Salivary Gland Tumors.

Patients with NTRK-rearranged tumors can be now treated using anti-TRK-targeted therapies making NTRK testing important for treatment choices in patients with advanced cancers. Pan-TRK immunohistochemistry (IHC) could be a valuable premolecular screening strategy in this field. The choice of 1 IHC method or another requires to investigate for intermethod comparison. A high frequency of pan-TRK positive tumors among salivary gland tumors makes these tumors particularly appropriate for such a technical study. In this work, we studied the intermethod agreement for 2 pan-TRK IHC methods (using A7H6R and EPR17341 clones) in a file of salivary gland tumors of different subtypes. Among 71 tumors, pan-TRK IHC was diagnosed as positive (ie, H score ≥5) in 23 and 18 cases using EPR17341 and A7H6R clones, respectively, with a good intermethod agreement in terms of positive/negative result (κ, 0.70) but only a moderate agreement considering the H score values themselves (intraclass correlation coefficient of 0.5399). Beyond the intensity of staining and the percentages of stained cells, major differences were also observed between the location and type of cells stained in positive cases between the 2 clones. The single NTRK-rearranged case in our series (ie, a NTRK3-rearranged salivary secretory carcinoma) was positive with the 2 pan-TRK antibodies. Future studies including molecularly proven NTRK-rearranged tumors remain required to further study and compare the performances of different pan-TRK clones in the screening of NTRK-rearranged cancers but it is now obvious that the staining patterns of A7H6R and EPR17341 clones are not strictly identical.

Non-secretory breast carcinomas lack NTRK rearrangements and TRK protein expression.

Anti-TRK targeted therapies offer opportunities to treat patients with advanced NTRK1/2/3-rearranged cancers. Beyond NTRK-rearranged secretory breast carcinomas, little is known about NTRK rearrangements and the expression of TRK proteins in non-secretory breast carcinomas. We search for TRK proteins expressions using pan-TRK immunohistochemistry and NTRK1, NTRK2 and NTRK3 rearrangements using fluorescent in situ hybridization (FISH) tests in a set of tissue microarray included breast carcinomas. Only 1/339 invasive breast carcinomas, the only example of secretory subtype, was positive using pan-TRK immunohistochemistry and harboured a NTRK-rearrangement (NTRK1 positive FISH test). According to our results, druggable NTRK rearrangements and related-TRK proteins expression are not encountered in non-secretory breast carcinomas.

Nonpuerperal uterine inversion due to adenomyosis: A case report and a literature review.

Nonpuerperal uterine inversion is a very rare event. We reported on the first ever case of nonpuerperal uterine inversion due to adenomyosis. Magnetic resonance imaging is recommended in cases with an unusual vaginal mass, so that this possible uterine etiology can be taken into consideration.

Prolonged Overall Treatment Time and Lack of Skin Rash Negatively Impact Overall Survival in Locally Advanced Head and Neck Cancer Patients Treated with Radiotherapy and Concomitant Cetuximab.

BACKGROUND: Cetuximab, a chimeric monoclonal antibody against EGFR sensitizes tumors to radiotherapy (RT), but is associated with skin and mucosal toxicity. OBJECTIVE: We report outcomes and tolerance of definitive RT in association with cetuximab in patients with locally advanced squamous cell carcinoma (LASCC) of the head and neck. PATIENTS AND METHODS: Between 2006 and 2011, 92 consecutive patients with LASCC of the head and neck were treated with RT and concomitant weekly cetuximab. Median age was 61.7 years. Most patients presented with oropharyngeal tumors (52.2%) and stage IV disease (77.2%). RESULTS: Sixty-nine patients received at least 7 cycles of cetuximab. Cetuximab was stopped at the first infusion following allergic reactions in four patients. During RT, 37% of patients developed grade ≥ 3 dermatitis; grade ≥ 2 cetuximab-induced rash occurred in 43 patients (46.7%). Severe mucositis (grade ≥ 3) affected 57.6% of patients. Ten percent of patients did not receive the full course of RT, and temporary discontinuation due to acute toxicity was frequent and affected 37 patients (53%). The median RT overall treatment time (OTT) in patients with interrupted RT was 56 days (47-75) compared to 51 days (47-65) in patients who did not require toxicity-related radiation interruptions (p < 0.05). After a median follow-up of 17.5 months (1.3-107.6) for all patients, median overall survival was 17.9 months (95% CI: 12.7-23.2), and loco-regional control (LRC) was 9.2 months (95% CI: 3.9-14.4). On multivariate analysis, hemoglobin concentration and occurrence of rash grade ≥ 2 were independent prognostic factors for LRC (p = 0.023 and p = 0.006, respectively). Lack of rash and extended OTT negatively impacted overall survival (p = 0.048 and 0.052, respectively). CONCLUSIONS: Skin and mucosal toxicity remains an issue in patients with LASCC of the head and neck treated with concomitant cetuximab and RT. Severe toxicity leads to treatment interruptions and prolonged overall treatment time, with consequent decreased overall survival in these patients.

Cosmetic Outcome and Chronic Breast Toxicity After Intraoperative Radiation Therapy (IORT) as a Single Modality or as a Boost Using the Intrabeam® Device: A Prospective Study.

PURPOSE: We aim to report our results in terms of chronic toxicities and cosmetic outcomes after intraoperative radiotherapy (IORT) using kV X-rays in women treated for early breast cancer at our institution. METHODS: Patients with early breast carcinoma were recruited between April 2011 and November 2014. After breast-conserving surgery, patients were treated with IORT using the Intrabeam® device. IORT was completed by whole-breast radiotherapy (WBRT) at a dose of 46-50.4 Gy in 23-28 fractions in case of adverse pathologic criteria on the final specimen examination. Skin toxicity was graded using the Late Effects in Normal Tissues-Subjective, Objective, Management and Analytic (LENT-SOMA) scale every 6 months, and cosmetic outcomes were evaluated at 36 months by patient self-evaluation and by two radiation oncologists, on a 1-10 scale. RESULTS: Forty-one women received IORT only and 30 patients received IORT followed by WBRT (IORT + WBRT group). After a median follow-up of 38.9 months, no locoregional or distant recurrence occurred. After IORT only, 2.4% of grade 2 or higher breast fibrosis, and no other grade 2 or higher disease, was observed. In the IORT + WBRT group, grade 2 or higher fibrosis and grade 2 or higher breast retraction were observed in 43.3 and 23.3% of patients, respectively. Objective cosmetic outcomes were very good and significantly better in the IORT-only group compared with the IORT + WBRT group (8.87 vs. 6.96) (p < 0.001). CONCLUSION: IORT using the Intrabeam® is well-tolerated, with very little chronic toxicity and good cosmetic outcome. However, a high rate of grade 2 or higher chronic breast toxicity was observed when IORT had to be completed by WBRT.

Breast implant-associated anaplastic large-cell lymphoma can be a diagnostic challenge for pathologists.

BACKGROUND: Primary anaplastic large-cell lymphoma (ALCL) occurring in women with breast implants is very rare. It is usually described as tumor cells infiltrating the periprosthetic capsule. These are most often revealed by a periprosthetic recurrent isolated effusion (seroma cavity), occurring late after implantation of the prosthesis. ALCL is more rarely a tumor or periprosthetic capsular contracture. CASE: We report a 66-year-old woman, initially diagnosed by cytological examination of breast effusion, in whom ALCL appeared two and a half months after the removal of a ruptured implant. Repeated biopsies of the periprosthetic capsule performed in parallel showed fibrous tissue, without tumor proliferation. Only meticulous histological examination of the total capsulectomy identified tumor cells as a thin and discontinuous layer along the inner surface of the capsule without capsular invasion. CONCLUSION: Awareness of the histological pattern of this new clinical entity is important. A total capsulectomy with a good sampling for microscopic examination should be conducted for any suspicion of breast implant-associated ALCL. Cytology-histology correlation is essential.

Hodgkin's disease masquerading as fibrous thyroiditis: potential role of cytokines in in vivo and in vitro studies.

Hodgkin's disease appearing as, or associated with, fibrous thyroiditis has only been described rarely. We report the observation of a patient presenting with a goitre, fibrosis of the thyroid and adjacent structures, and hypothyroidism. The histological examination was compatible with fibrosclerotic thyroiditis. This diagnosis was reviewed 6 months later when the biopsy of a supraclavicular nodule that had subsequently appeared led to the diagnosis of a nodular-sclerosis type of Hodgkin's disease. The plasmatic levels of interleukin 6 (IL-6) and tumour necrosis factor alpha (TNF-alpha) were very high compared to the levels in healthy subjects (12 and 40 IU/l vs. 0.05 and 2.0 IU/l, respectively). These cytokine levels decreased when the initial illness was treated, and their normalization was associated with the disappearance of the cervical and thyroidal fibroses. A parallel in vitro study of these cytokines and of TNF-alpha receptors and IL-13 was performed. The results suggest a possible cause-and-effect relationship between IL-6 and IL-13 produced locally by the tumoral tissue and the development of cervical fibrosis.

[Peritoneal glioblastoma: recurrence of ovarian immature teratoma (report of a case)]. / Glioblastome péritonéal: récidive d'un tératome immature de l'ovaire (à propos d'un cas).

Immature teratomas of the ovary represent less than 1% of all ovarian teratomas. They contain several tissues that derive from the three embryological layers: ectoderm, mesoderm and endoderm. They are rarely associated with peritoneal implants that are essentially composed of mature glial tissue, and of benign evolution. We report the case of a 37-year- old woman who presented an immature teratoma of the right ovary that recurred seven years later as a malignant neuroepithelial peritoneal tumor resembling a glioblastoma. Glioblastoma was diagnosed at a second recurrence six months later. We discuss the histopathogenesis of peritoneal implants secondary to immature teratomas.