High rate of PIK3CA mutations but no TP53 mutations in low-grade adenosquamous carcinoma of the breast.

AIMS: Low-grade adenosquamous carcinoma of the breast (LGASC) is a rare variant of metaplastic carcinoma characterised by a favourable outcome and histologically composed of glandular and squamous elements in a spindle cell background typically associated with a lymphocytic stromal reaction. Because of its rarity, the immunophenotypic and genetic profile of LGASC has not been sufficiently characterised. The aim of this study was to gain insights into the molecular and phenotypic characteristics of LGASC. METHODS AND RESULTS: We reviewed the clinical and morphological features and detailed the immunohistochemical characteristics of a retrospective series of 13 LGASCs. Targeted sequencing of 50 genes was performed in 10 of 13 cases. Identified mutations were further assessed by Sanger sequencing in a validation series of 11 additional cases. All tumours showed a triple-negative immunophenotype, expressed 'basal' keratins, showed variable levels of epidermal growth factor receptor expression, and did not express androgen receptor. Sequencing analysis of the screening set of LGASCs revealed a high rate (seven of 10 cases) of PIK3CA mutations, whereas no TP53 mutations were found. All PIK3CA mutations were missense mutations located either in exon 20 (n = 6) or in exon 9 (n = 1). The global PIK3CA mutation rate, including the validation series, was 52% (11 of 21 cases). No disease recurrences were observed. [Correction added on 11 June 2018, after first online publication: The percentage of mutation rate was corrected to 52%] CONCLUSIONS: Our results indicate that LGASC of the breast is a low-grade triple-negative breast cancer that harbours a basal-like phenotype with no androgen receptor expression, and shows a high rate of PIK3CA mutations but no TP53 mutations.

[The RENAPE network: towards a new healthcare organization for the treatment of rare tumors of the peritoneum. Description of the network and role of the pathologists]. / Réseau RENAPE : vers une nouvelle organisation des soins pour le traitement des tumeurs rares du péritoine. Description du réseau et rôle des pathologistes.

As part of the national 2009-2013 Cancer Plan, and with the support of the National cancer Institute and the French ministry of health, the National network for the treatment of rare peritoneal malignancies (RENAPE) has been organized. Its main objective is to optimize the framework for the healthcare management and treatment of rare peritoneal malignancies. This specific organization covers the whole national territory including clinical expert and specialized structures and should lead to an appropriate treatment based on expertise and proximity. Within the RENAPE network, the RENA-PATH group gathers the pathologists actively involved in the management of rare peritoneal malignancies. The actions of RENA-PATH are focused primarily on the harmonization of pathological diagnostic criteria, reporting of new cases in the RENAPE registry and histology reviewing.

[Peritoneal pseudomyxoma: an overview emphasizing pathological assessment and therapeutic strategies]. / Mise au point sur le pseudomyxome péritonéal. Aspects anatomo-pathologiques, et implications thérapeutiques.

Pseudomyxoma peritonei is a clinical entity characterized by a gelatinous ascite associated with mucinous tumor deposits spreading on peritoneal surface and potentially invading abdominal organs. It is considered as a tumor process linked, in most of cases, to a mucinous appendiceal neoplasm. Pseudomyxoma peritonei may benefit from a therapeutic strategy combining cytoreductive surgery and intra-peritoneal chemotherapy, which has led to a major prognosis improvement. Different classifications are available and the last one corresponds to the WHO 2010 version, which individualizes pseudomyxoma peritonei in two classes: low grade and high grade mucinous carcinoma. The very low frequency of this entity and its specific therapeutic strategy need specific health care centres, as well as physicians and pathologists collaborating through dedicated networks. The aim of this article is to summarize the pathology, causes, mechanisms and therapeutic approaches of pseudomyxoma peritonei, as well as their interfaces with dedicated networks.

[Peritoneal malignant mesothelioma: review and recent data]. / Mésothéliome malin péritonéal : mise au point et données actuelles.

Peritoneal malignant mesothelioma is a rare tumor, less common than its pleural counterpart. It develops from the mesothelial cells overlying peritoneum and preferentially occurs in male, with an average age ranging from 47 to 60.5 years. Asbestos whose impact is less strong than in pleural mesothelioma, SV 40 virus, chronic peritonitis could be implicated as factors favoring the development of peritoneal mesothelioma. Clinical symptoms are not specific, and the imagery remains little or not contributive. The 2004 WHO classification recognizes 3 different types, which differ in terms of presentation and prognosis: diffuse epithelioid mesothelioma (the most common), sarcomatoid mesothelioma and biphasic mesothelioma. Many variants are described within these groups. Immunohistochemistry is mandatory to affirm or disprove peritoneal malignant mesothelioma diagnosis, based on a panel of antibodies divided in positive markers and negative markers. Indeed an accurate diagnosis is necessary to define a therapeutic strategy more and more frequently based on the combination of radical surgery and hyperthermic intra peritoneal chemotherapy. Such an approach significantly improves the prognosis of these aggressive diseases.

[Cellular and molecular mechanisms of carcinogenic side effects and resistance to BRAF inhibitors in metastatic melanoma with BRAFV600 mutation: state of the knowledge]. / Effets secondaires carcinogènes et résistances aux thérapies ciblées anti-BRAF.

Cutaneous melanoma is a malignant tumor with a high metastatic potential. If an early treatment is associated with a favorable outcome, the prognosis of metastatic melanoma remains poor. Advances in molecular characterization of cancers, notably the discovery of BRAF gene mutations in metastatic melanoma, allowed to the recent development of targeted therapies against mutated BRAF protein. Despite high tumor response rates observed in clinical trials, these new drugs are associated with frequent secondary tumor resistance occurrence and paradoxical carcinogenic side effects. The cellular and molecular mechanisms of these carcinogenic side effects and secondary resistance are not yet fully elucidated and are actually intensely studied. This review of the literature focus on the mechanisms of these carcinogenic side effects and on the tumor resistance associated with anti-BRAF targeted therapies.

Primary breast non-Hodgkin's lymphoma: a large single center study of initial characteristics, natural history, and prognostic factors.

The aims of this study were to define the initial pathological and clinical characteristics, and prognostic factors of patients with primary breast malignant lymphoma (PBL). All patients treated at the Institut Curie for lymphoma with breast involvement were reviewed. A pathological review of all cases was performed. Forty-five cases were selected in whom 38 cases were of diffuse large B-cell lymphoma. A complete analysis was then performed on these 38 patients. Twenty out of 28 cases (71%) of cases were Bcl-2 positive and four out of 28 (14%) had a CD10 positive staining. Peculiar initial characteristics showed nodal involvement in 58% of the cases and two or more extra-nodal sites in 31% of the cases. Among the 37 patients for whom all data were available, and according to the International Prognostic Index, 19 patients (51%) were classified in the low-risk group, 5 cases (14%) in the low- to intermediate-risk group, 6 patients (16%) in the intermediate- to high-risk group, and 7 (19%) case in the high-risk group. At the end of initial therapy, 34 patients (89%) achieved CR. With a median follow-up of 96 months, 18 patients (47%) relapsed of whom 3 had a relapse in central nervous system site. The 5-year disease-free (DFS) and overall survivals (OS) were 54% and 61%, respectively. In multivariate analysis, the presence of 2 or more extranodal sites was prognostic for lower DFS (P = 0.0008) and OS (P = 0.09), and a performance status > or = 1 was prognostic for lower OS (P = 0.005). Finally, when our series was compared with a historical series of 111 patients with aggressive nodal lymphomas, we observed significant lower survival rates in localized PBL (P < 0.03). Initial breast localization has a pejorative impact on the outcome of patients with Non-Hodgkin's Lymphoma (NHL), with an impressive adverse influence of additional extranodal sites. These results suggest a specific management of NHL with breast involvement.

Loss of chromosomes 9 and 11 may be recurrent chromosome imbalances in juxtaglomerular cell tumors.

Juxtaglomerular cell tumor (JGCT), first described in 1967, is a rare tumor of the kidney that derived from specialized smooth muscle cells of the wall of the glomerular afferent arteriole. Less than 100 cases have been published, mainly as isolated case reports or small series. JGCTs are considered benign, but the clinical follow-up is short in most reported cases. Only 1 metastatic case has been reported to date, raising the question of tumors of uncertain malignant potential rather than clearly benign neoplasms. Genomic features have been studied in only 2 cases that showed gain of chromosome 10 as well as loss of chromosomes 9, 11q, and X. The present work studied the genomic characteristics of 2 additional cases of JGCT by comparative genomic hybridization. Similarly to the 2 previously reported cases, these 2 tumors showed loss of chromosomes 9 and 11, suggesting recurrent chromosomal imbalances. In addition, 1 case showed gain and loss of entire chromosomes, similar to a previous case studied by karyotyping. Such an aneuploid karyotype may reflect a potential for malignancy as previously reported. Thus, JGCT might be better considered as a tumor of uncertain malignant potential and then necessitates a prolonged follow-up. Future clinicopathologic and genomic studies of large retrospective and prospective series may help to better understand the biology of this fascinating entity.

Synchronous FIP1L1-PDGFRA-positive chronic eosinophilic leukemia and T-cell lymphoblastic lymphoma: a bilineal clonal malignancy.

Several reports of successful empirical treatment of idiopathic hypereosinophilic syndrome with imatinib led to the recent identification of the FIP1L1-PDGFRA fusion gene rearrangement, which characterizes a distinctive group of chronic eosinophilic leukemias. This fusion gene can be detected in eosinophils, neutrophils, mast cells, T cells, B cells and monocytes in FIP1L1-PDGFRA-positive hypereosinophilic patients suggesting a multilineage involvement. Furthermore, the same FIP1L1-PDGFRA rearrangement was identified in patients with hypereosinophilia and atypical mast cell proliferations, raising the question of a disease with two concomitant lines of differentiation. In addition, a recent report noted two cases with the association of FIP1L1-PDGFRA-positive chronic eosinophilic leukemia and T-cell lymphoblastic lymphoma (T-LBL). We report here the only third case of synchronous chronic eosinophilic leukemia and T-LBL, both associated with a FIP1L1-PDGFRA fusion transcript, confirming the occurrence of such disease and suggesting a clonal proliferation with two lines of differentiation probably arising from a primitive multipotent medullary stem cell.

[Juxtaglomerular cell tumors: report of two cases with genomic analysis]. / Tumeur à rénine du rein : à propos de deux cas, avec analyse génomique.

Juxtaglomerular-cell tumor (JGCT), first described in 1967, is a rare tumor of the kidney that derives from specialized smooth-muscle cells of the wall of the glomerular afferent arteriole. Less than 100 cases have been published, mainly as single-case reports or small series. JGCTs are considered benign, but the clinical follow-up has been short in most reported cases. Only one metastatic case has been reported to date, raising the question of tumors of uncertain malignant potential rather than clearly benign neoplasms. Genomic features have been studied in only two cases that showed gains on chromosome 10 as well as deletions on chromosomes 9, 11q and X. The present work studied the genomic characteristics of two additional cases of JGCT by CGH. Similarly to the two previously reported cases, these two tumors showed losses on chromosomes 9 and 11, suggesting recurrent chromosomal imbalances. In addition, one case showed gains and losses of entire chromosomes similar to a previous case studied by karyotyping. Such an aneuploid karyotype may reflect a potential for malignancy as previously reported. Thus, JGCT might be better considered as a tumor of uncertain malignant potential consequently requiring a prolonged follow-up. Future clinicopathologic and genomic studies of large retrospective and prospective series may help to better understand the biology of this fascinating entity.

Late cerebellar relapse of a juvenile bronchial carcinoid.

Although epithelial bronchial neoplasm is a cancer frequently observed in adult patients, it is rarely observed in patients who are children. The most frequent histologic subtype is well differentiated neuroendocrine tumor, or carcinoid. They have a variable biologic behavior, ranging from benign to malignant tumors capable of very late recurrence or metastasis. Liver and lung are frequent sites of carcinoid metastasis, and the central nervous system is exceptionally involved. We report the case of a child with a pulmonary carcinoid initially considered typical, who presented with relapse in the cerebellum and mediastinum 16 years later. After review of the pathology slides, primary and metastatic tumors were reclassified as atypical carcinoid according to the criteria of the 2004 World Health Organization classification of lung tumors. This unusual case emphasizes the value of reviewing pulmonary carcinoids diagnosed before 1998 in order to distinguish typical from atypical lesions and to define follow-up modalities more clearly.

Chronic monoarthritis and previous history of cancer: think about synovial metastasis.

Synovial metastases are rare events. Only 37 cases diagnosed by synovial fluid cytologic examination and/or by microscopic investigation of synovial biopsies have been previously reported in the literature. We report another case of shoulder chronic arthritis due to a recurrence of rectal adenocarcinoma and review previous published observations. Generally, this condition carries a poor prognosis with average patients survival of less than 5 months. The possibility of metastatic disease should be considered when an elderly person or patient with a history of previous malignancy presents with a chronic arthritis.

Pleomorphic hyalinizing angiectatic tumor of soft parts: ultrastructural analysis of a case with original features.

Pleomorphic hyalinizing angiectatic tumor, a rare neoplasm of uncertain lineage resembling malignant fibrous histiocytoma and schwannoma, was first described in 1996 by M. E. F. Smith et al. (Am Surg Pathol. 20:21-29). To date, less than 100 cases have been reported in the international literature. It occurs in subcutaneous and intramuscular soft tissues of extremities or trunk in adults without sex predilection. All lesions are composed of sheets and fascicles of spindled and pleomorphic cells associated with clusters of thick-walled ectatic vessels surrounded by a perivascular hyaline material and inflammatory cells such as mast cells. About one-half of these neoplasms express CD34. No patient has developed metastases but occasional local recurrences are possible. This tumor of uncertain lineage is suggested to be an aggressive locally growing low-grade sarcoma. Only 3 cases were previously studied by electron microscopy and appeared to consist of primitive fibroblastic cells. The authors report histological and ultrastructural characteristics of a new case of PHAT excised from the right buttock of a 66-year-old man with the presence of ganglion-like cells, a feature that has not been previously reported, and unusual central ischemic necrosis. The features of this case are suggestive of a fibroblastic origin.

[Post-cholecystectomy amputation neuroma of the common bile duct with obstructive jaundice]. / Sténose post-opératoire de la voie biliaire principale due à un névrome d'amputation post-cholécystectomie.

Amputation neuroma of the common bile duct after surgery is a rare and mostly asymptomatic lesion. A 60-year old patient presented with obstructive jaundice three months after a cholecystectomy for symptomatic gallstones. Imaging investigations showed common extrahepatic bile duct stenosis. Surgical resection of the stricture with biliodigestive anastomosis was performed. Histological examination of the surgical specimen revealed an amputation neuroma. Despite its rarity, amputation neuroma of the common bile duct should be considered in patients with post-cholecystectomy syndrome following liver or extrahepatic bile duct surgical procedures.

An original cause of drowning in an industrial environment.

We describe an original case of drowning in a wax tank in an industrial setting. The causes of death were multiple, with the association of drowning, mechanical asphyxia, and extensive superficial burns. To our knowledge, it is the first report of drowning in wax, and only 7 previous related observations of drowning in industrial environments were reported in the international literature. These accidents are more often fatal, with multiple associated causes of death due to the incriminated media. Although exceptional, these serious accidents must be prevented in potentially risky industries.