Vanessa Szablewski

Adult sinonasal soft tissue sarcoma: Analysis of 48 cases from the French Sarcoma Group database

The aim of this study was to determine the frequency of primary sinonasal adult sarcoma, identify histological subtypes, and analyze prognostic factors.

EGFR Expression and KRAS and BRAF Mutational Status in Intestinal-Type Sinonasal Adenocarcinoma.

Accumulation of molecular alterations, including EGFR overexpression and mutations in KRAS and BRAF, contribute to colorectal carcinogenesis. Since intestinal-type adenocarcinoma (ITAC) of the nasal cavity and paranasal sinus has morphologic and phenotypic features that are usually indistinguishable from colorectal cancer (CRC), it is likely that both tumor types share equivalent genetic alterations. Data from a series of 43 patients treated surgically for ITAC in Montpellier, France between November 1998 and December 2012 were collected. Tumors were characterized for mutations in KRAS and BRAF as well as EGFR overexpression. Kaplan-Meier survival curves were constructed using overall survival as the primary end points. Patient survival was analyzed using the hazards ratio. Twenty seven tumors (63%) showed EGFR positivity and 30% exhibited a high expression level (+2/+3). KRAS mutations were detected in 43% of cases. BRAF mutations were identified in 3.6% of specimens. Patients with age superior to 60 years, metastatic status, and KRAS mutations had significant overall survival values (p = 0.026, p = 0.001 and p = 0.03, respectively). Our results indicate that KRAS mutations and EGFR expression are frequent in ITAC and that KRAS mutations predict good patient prognosis in ITAC. Finally, EGFR directed molecular treatments could be investigated in a subset of patients affected by ITAC.

R-CHOP 14 with or without radiotherapy in nonbulky limited-stage diffuse large B-cell lymphoma

The benefit of radiotherapy (RT) after chemotherapy in limited-stage diffuse large B-cell lymphoma (DLBCL) remains controversial. We conducted a randomized trial in patients with nonbulky limited-stage DLBCL to evaluate the benefit of RT after rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). Patients were stratified according to the modified International Prognostic Index, including lactate dehydrogenase, Eastern Cooperative Oncology Group performance status, age, and disease stage. The patients received 4 or 6 consecutive cycles of R-CHOP delivered once every 2 weeks, followed or not by RT at 40 Gy delivered 4 weeks after the last R-CHOP cycle. All patients were evaluated by fluorodeoxyglucose-positron emission tomography scans performed at baseline, after 4 cycles of R-CHOP, and at the end of treatment. The primary objective of the trial was event-free survival (EFS) from randomization. The trial randomly assigned 165 patients in the R-CHOP arm and 169 in the R-CHOP plus RT arm. In an intent-to-treat analysis with a median follow-up of 64 months, 5-year EFS was not statistically significantly different between the 2 arms, with 89% ± 2.9% in the R-CHOP arm vs 92% ± 2.4% in the R-CHOP plus RT arm (hazard ratio, 0.61; 95% confidence interval [CI], 0.3-1.2; P = .18). Overall survival was also not different at 92% (95% CI, 89.5%-94.5%) for patients assigned to R-CHOP alone and 96% (95% CI, 94.3%-97.7%) for those assigned to R-CHOP plus RT (P = not significant). R-CHOP alone is not inferior to R-CHOP followed by RT in patients with nonbulky limited-stage DLBCL. This trial was registered at www.clinicaltrials.gov as #NCT00841945.

Detection of known and novel ALK fusion transcripts in lung cancer patients using next-generation sequencing approaches

Rearrangements of the anaplastic lymphoma kinase (ALK) gene in non-small cell lung cancer (NSCLC) represent a novel molecular target in a small subset of tumors. Although ALK rearrangements are usually assessed by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH), molecular approaches have recently emerged as relevant alternatives in routine laboratories. Here, we evaluated the use of two different amplicon-based next-generation sequencing (NGS) methods (AmpliSeq and Archer®FusionPlex®) to detect ALK rearrangements, and compared these with IHC and FISH. A total of 1128 NSCLC specimens were screened using conventional analyses, and a subset of 37 (15 ALK-positive, and 22 ALK-negative) samples were selected for NGS assays. Although AmpliSeq correctly detected 25/37 (67.6%) samples, 1/37 (2.7%) and 11/37 (29.7%) specimens were discordant and uncertain, respectively, requiring further validation. In contrast, Archer®FusionPlex® accurately classified all samples and allowed the correct identification of one rare DCTN1-ALK fusion, one novel CLIP1-ALK fusion, and one novel GCC2-ALK transcript. Of particular interest, two out of three patients harboring these singular rearrangements were treated with and sensitive to crizotinib. These data show that Archer®FusionPlex® may provide an effective and accurate alternative to FISH testing for the detection of known and novel ALK rearrangements in clinical diagnostic settings.

PD1 and PDL1 expression in primary central nervous system diffuse large B‐cell lymphoma are frequent and expression of PD1 predicts poor survival

Primary central nervous system diffuse large B‐cell lymphoma (PCNS‐DLBCL) is a rare and aggressive type of diffuse large B‐cell lymphoma (DLBCL) whit poorly understood pathogenesis. Finding biomarkers associated with patient survival may be important for understanding its physiopathology and to develop new therapeutic approaches. We investigated 32 PCNS‐DLBCL from immunocompetent patients for BCL2, CMYC, LMO2, and P53 expression and for cytogenetic aberrations of BCL2, BCL6, and MYC genes, all known for their prognostic value in systemic DLBCL (s‐DLBCL). We analyzed PD1 and PDL1 protein expression in both tumor infiltrating lymphocytes (TILs) and tumor cells. Finally, we searched for correlation between biological data and clinical course. The PCNS‐DLBCL expressed BCL2, CMYC, LMO2, and P53 at similar frequency than s‐DLBCL but without significant prognostic on survival. None cases harbored aberrations involving BCL2 and MYC gene whereas BCL6 abnormalities were present in 20.7% of cases but without value on survival. Expression of PD1 in TILs and PDL1 in tumor cells was observed at higher rates than in s‐DLBCL (58% and 37%, respectively). The PD1 expression in TILs correlated with PDL1 expression in tumor cells (P = .001). Presence of PD1 positive TILs was associated with poorer overall survival (P = .011). Patients with PDL1 overexpression tended to better response to chemotherapy (P = .23).

Diagnostic value of STMN1, LMO2, HGAL, AID expression and 1p36 chromosomal abnormalities in primary cutaneous B cell lymphomas

Distinction between primary cutaneous follicular lymphoma (PCFL) and primary cutaneous marginal zone lymphoma (PCMZL) is challenging, as clear‐cut immunophenotypical and cytogenetic criteria to segregate both entities are lacking.

Lymph node location of a clear cell hidradenoma: report of a patient and review of literature.

Cutaneous clear cell hidradenoma is an uncommon benign adnexal tumor which is not supposed to metastasize, contrary to its rare malignant counterpart, hidradenocarcinoma. We report the case of a 49‐year‐old man, who had had a stable inguinal lymph node enlargement for 6 years. An excision was performed and revealed an intra‐nodal tumor, made of large clear cells with abundant cytoplasm and round nuclei without atypia or mitosis. The immunohistochemical staining showed diffuse positivity for keratin AE1/AE3, keratin 5/6 and p63, and focal staining with keratin 7, epithelial membrane antigen (EMA) and carcinous epithelial antigen (CEA), which underlined some ductular structures. Tumor cells were negative for renal markers PAX8 and CD10. Ki67 stained less than 1% of tumor cells. A translocation involving MAML2 gene was evidenced by fluorescence in situ hybridization (FISH) analysis. No primary cutaneous tumor was found after extensive examination. Altogether, these results are in favor of an isolated nodal hidradenoma, for which we discuss two hypothesis: a primary nodal lesion, or a ‘benign metastasis’ of a cutaneous tumor. Cases of morphologically benign hidradenoma with lymph node involvement are exceptional. Our case, similar to every other reported case, was associated with an excellent prognosis, supporting the idea that these patients should not be overtreated.

Indolent cytotoxic T cell lymphoproliferation associated with nodular regenerative hyperplasia: a common liver lesion in the context of common variable immunodeficiency disorder

Patients with common variable immunodeficiency disorder (CVID) are subject to lymphoproliferative disorders and predisposed to lymphoma. Some patients may also develop liver lesions. The purpose of this study was to define clinical and histopathological features of patients with CVID presenting with liver lesions suspicious of lymphoma. Four CVID cases corresponding to these criteria were retrieved from our files. Liver biopsy specimens were subjected to morphologic, immunophenotypic and molecular analysis. All patients presented with hepatosplenomegaly and two furthermore with lymphadenopathy. The clinical working diagnosis in the four cases was lymphoma. All liver biopsies revealed nodular regenerative hyperplasia (NRH), associated with mild to marked sinusoid lymphocytic infiltrate consisting of “activated” cytotoxic T cells (CD8+, Tia1+, granzyme B+, TCRβF1+, CD56-). EBER was negative in all cases. T cell clonality was found in one of the two interpretable cases. All patients had an indolent course and clinical symptoms regressed with immunoglobulin replacement. This study suggests that indolent proliferation in the liver sinusoid of cytotoxic T cell associated with NRH is a specific liver lesion in the context of CVID. In CVID patients clinically suspected of lymphoma, pathologists should avoid a misdiagnosis of aggressive T cell lymphoma with a risk of over treatment.

Factors influencing extramedullary relapse after allogeneic transplantation for multiple myeloma

Factors influencing extramedullary relapse after allogeneic transplantation for multiple myeloma

Cutaneous presentation preceding acute myeloid leukemia with CD4+/CD56+ expression misdiagnosed as a blastic plasmocytoid dendritic cell neoplasm: A case report

Acute myeloid leukemia (AML) may initially present as cutaneous lesions corresponding to blasts involving the skin as the first clinical manifestation prior to blood and bone marrow (BM) infiltration. Such presentation is known as myeloid leukemia cutis (LC). Blastic plasmocytoid dendritic cell neoplasm (BPDCN) is an aggressive tumor derived from the precursors of plasmocytoid dendritic cells with cutaneous and BM involvement and leukemic dissemination. Myeloid LC and BPDCN may be difficult to distinguish as they share similar clinical and histopathological features, in particular AML with monocytic differentiation. Nevertheless, the correct diagnosis has to be made to determine adequate and effective therapy. Here, we report the case of a 61‐year‐old woman who presented with an AML with MLL rearrangement and CD4+/CD56+ expression presenting as LC and that was misdiagnosed as BPDCN. We emphasize that careful and exhaustive analyses should be performed to make the correct diagnosis.