Cytopathological analysis of salivary gland cancer: REFCOR recommendations by the formal consensus method.

OBJECTIVE: To determine the indications for fine-needle cytology and the modalities of frozen section pathological analysis in the management of salivary gland cancer. MATERIAL AND METHODS: The French Network of Rare Head and Neck Tumors (REFCOR) formed a steering group who drafted a narrative review of the literature published on Medline and proposed recommendations. The level of adherence to the recommendations was then assessed by a rating group according to the formal consensus method. RESULTS: Fine-needle cytology is recommended as part of the diagnostic work-up for a major salivary gland tumor suspicious for malignancy. Fine-needle cytology should be performed after MRI to avoid artifacts. Frozen section analysis is recommended to confirm the malignant nature of the tumor, to adapt the extent of resection and to indicate neck dissection. Whenever possible, the entire tumor and adjacent salivary or periglandular tissue should be sent for frozen section analysis. CONCLUSION: Fine-needle cytology and frozen section analysis play an essential role in the management of salivary gland cancers.

Outcomes of active surveillance of EU-TIRADS 5 thyroid nodules.

OBJECTIVE: Active surveillance of cytologically proven microcarcinomas has been shown as a safe procedure. However, fine needle aspiration biopsy (FNAB) is not recommended by European Thyroid Association (ETA) and American Thyroid Association (ATA) guidelines for highly suspicious nodules ≤ 10 mm. The aim of the study was to assess the outcomes of active surveillance of EU-TIRADS 5 nodules ≤ 10 mm not initially submitted to FNAB. PATIENTS AND METHODS: 80 patients with at least one EU-TIRADS 5 nodule ≤ 10 mm and no suspicious lymph nodes, accepting active surveillance, were included. RESULTS: Mean baseline diameter and volume were 5.4 mm (±2.0) and 64.4 mm3 (±33.5), respectively. After a median follow-up of 36.1 months, a volumetric increase ≥ 50% occurred in 28 patients (35.0%) and a suspicious lymph node in 3 patients (3.8%). Twenty-four patients underwent an FNAB (30.0%) after at least a 1 year follow-up of which 45.8% were malignant, 8.3% benign, 33.3% undetermined and 8.3% nondiagnostic. Sixteen patients (20.0%) underwent conversion surgery after a median follow-up of 57.2 months, confirming the diagnosis of papillary carcinoma in 15/16 cases (not described in 1 histology report), all in remission at 6-12 months postoperative follow-up. CONCLUSION: Applying ETA and ATA guidelines to avoid FNA of EU-TIRADS 5 sub-centimeter nodules and proceeding to active surveillance of such nodules in selected patients is a safe procedure. Thus, US-FNAB could be postponed until the nodule shows signs of progression or a suspicious lymph node appears, with no added risk for the patient.

TIRADS score is of limited clinical value for risk stratification of indeterminate cytological results.

CONTEXT: Thyroid nodules with cytological indeterminate results represent a daily and recurrent issue for patient management. OBJECTIVE: The primary aim of our study was to determine if TIRADS (Thyroid Imaging Reporting and Data System) could be used to stratify the malignancy risk of these nodules and to help in their clinical management. Secondary objective was to estimate if this risk stratification would change after reclassification of encapsulated non-invasive follicular variant of papillary carcinomas (FVPTC) as non-invasive follicular thyroid neoplasm (NIFTP). PATIENTS AND METHODS: Single-center retrospective study of a cohort of 602 patients who were referred for ultrasound-guided fine-needle aspiration from January 2010 to December 2016 with an indeterminate cytological result and in whom histological results after surgery were available. TIRADS score was prospectively determined for all patients included. Nodules that had been classified as FVPTC were submitted to a rereading of histological report and reclassified as NIFTP when judged relevant. A table of malignancy risk crossing Bethesda and TIRADS results was built before and after this reclassification. RESULTS: The study included 602 cytologically indeterminate nodules. TIRADS score was positively correlated with the malignancy rate (P < 0.0001). Risk stratification with TIRADS was significant only in Bethesda V nodules (P = 0.0004). However, the risk of malignancy in this Bethesda V category was always above 45%, whatever the TIRADS score. CONCLUSION: For a clinician facing an indeterminate cytological result for a thyroid nodule, return to TIRADS score is of limited value in most conditions to rule in or rule out malignancy and to guide subsequent management of patients.

[The Thyroid Imaging Reporting and Data System (TIRADS) for ultrasound of the thyroid]. / Le système TIRADS en échographie thyroïdienne.

PURPOSE: To develop a standardized system for analyzing and reporting thyroid ultrasound, or Thyroid Imaging Reporting and Data System (TIRADS), in order to improve the management of patients with thyroid nodules. MATERIALS AND METHODS: An atlas of imaging features, a standardized vocabulary, a report template and TIRADS categories 0 to 6 were defined, based on the BI-RADS system used for mammography. The diagnostic efficacy of the system was tested by a retrospective review of 500 nodules (159 cancers and 341 benign nodules) and comparing US imaging features to histological findings. RESULTS: Five signs allow accurate detection of 90% of thyroid cancers. The score of a nodule can be easily defined by using an organigram. Sensitivity, specificity and odds-ratio of the score were respectively 95%, 68% and 40. CONCLUSION: TIRADS is a quality assurance tool for thyroid ultrasound. It contains an image atlas, a standardized report and categories to evaluate thyroid nodules to easily assess the risk of individual nodules being cancers and facilitate patient management.

[Multifocal nodular oncocytosis hyperplasia of the parotid gland]. / L'hyperplasie oncocytaire nodulaire multifocale de la glande parotide.

OBJECTIVES: Oncocytic lesions rarely affect the parotid gland, accounting for less than 1% of all salivary lesions. The WHO classification described three main types: diffuse oncocytosis, focal nodular oncocytosis hyperplasia, and oncocytoma. Multifocal nodular oncocytosis hyperplasia of the parotid gland represents an extremely rare, non-tumorous pathology of the parotid gland. MATERIAL AND METHODS: We report a case of multifocal nodular oncocytosis hyperplasia of the parotid gland in a 70-year-old woman who was referred for a left preauricular mass that had gradually increased in size over the last 2 years. No lymph node of the neck was palpable. RESULTS: MRI demonstrated multiple bilateral lesions of the parotid glands. Total parotidectomy, preserving the facial nerve, was performed. CONCLUSION: We discuss the physiopathology and the treatment of multifocal nodular oncocytosis hyperplasia and provide a review of the literature.

[Granular cell tumours (Abrikossoff's tumour) of the parotid region]. / Tumeur à cellules granuleuses (tumeur d'Abrikossoff) de la loge parotidienne.

BACKGROUND: Granular cell tumour (Abrikossoff's tumour) was first described by Abrikossoff in 1926. These tumours are rare and usually presents as a solitary lesion, located mainly in the subcutaneous tissue of the head and neck, and in the oral cavity (tongue). CASE REPORT: We report a rare case of a granular cell tumor of the parotid gland, in a 55-year old woman, who was referred with a left preauricular mass that had rapidly increased in size over 2 months. There was no cervical lymph adenopathy. RMI demonstrated a solitary lesion of the parotid gland. Surgical resection was performed. CONCLUSION: We discuss the classification, pathophysiology and the treatment of granular cell tumours through a review of the literature.

[Caruncular melanoma. Apropos of clinical case]. / Mélanome caronculaire. A propos d'une observation anatomo-clinique.

The clinicopathologic case of a 69-year-old-female patient with a big caruncular melanoma is reported. Tumor was excised surgically and underwent external conventional radiation therapy with no recurrence two years later. Histopathology endorsed the clinical diagnosis and thickness of the tumor measured 5.5 mm. The bad prognosis of the caruncular location was reinforced by the tumor thickness. A better knowledge of conjunctival melanomas characteristics might allow an earlier diagnosis and a better prognosis as irradiation following surgical treatment appears efficient on unifocal limited melanomas.

Sea-blue histiocyte syndrome in bone marrow secondary to total parenteral nutrition.

Clinical and hematological abnormalities can occur in patients receiving intravenous fat emulsions as part of a long-term parenteral nutrition; they consist of hepatosplenomegaly and peripheral blood cytopenia(s). These abnormalities lead to bone marrow examination which revealed numerous macrophages laden with blue staining pigment granules and separate lipid vacuoles, presenting the typical histochemical characteristics of sea-blue histiocytes. Thus, long-term parenteral nutrition including fat-emulsion sources may represent a further condition in addition to the wide variety of disorders which can be associated with sea-blue histiocytosis. Moreover, in view of its clinical and morphological presentation, this storage pathological state could be compared with the so-called sea-blue histiocyte syndrome described by Silverstein and colleagues.

[Mooren's ulcer following combined extracapsular crystalline lens extraction and trabeculectomy]. / Ulcère de Mooren après chirurgie combinée extraction extracapsulaire du cristallin et trabéculectomie.

We report the case of a 70-year-old patient who presented with Mooren's ulcer in her right eye following extracapsular cataract extraction combined with trabeculectomy. She was successfully treated by a sclerocorneal graft combined with a large conjunctival resection. Clinical and histological features, and therapeutic outcomes are discussed and compared to previously published data.

Sea-blue histiocyte syndrome in bone marrow secondary to total parenteral nutrition including fat-emulsion sources: a clinicopathologic study of seven cases.

Bone marrow examination revealed a lipid-laden histiocytosis in seven patients undergoing long-term total parenteral nutrition necessitated by extensive short-bowel surgical resection. Clinical abnormalities occurred during this treatment which required bone marrow examination. These included hepatosplenomegaly and peripheral blood cytopenia; the median time to the detection of these abnormalities was 64 months. The most striking change within the bone marrow was the presence of many pigment-laden histiocytes which had the typical morphology of sea-blue histiocytes seen in the so-called idiopathic sea-blue histiocyte syndrome. The occurrence of sea-blue histiocytosis in the bone marrow in association with long-term parenteral nutrition for short-bowel syndrome has not, to our knowledge, been reported previously and should now be considered in the differential diagnosis of bone marrow sea-blue histiocytosis.

Detection of bcl-2 rearrangement in HIV-related follicular lymphoid hyperplasia.

Rearrangement of the bcl-2 gene at the MBR (major breakpoint region) locus with the immunoglobulin heavy-chain joining region has been reported in a high proportion of follicular lymphomas. This rearrangement has also been reported in very few normal B cells of the blood, tonsils, follicular lymphoid hyperplasia (FLH) of the lymph nodes. HIV infection is often associated at the onset of the disease with FLH, but the presence of rearranged bcl-2 B cells in these lymph nodes has not been described. In using a standard PCR assay with Southern blot or a semi-nested PCR on 48 cases of FLH, we demonstrated that there were a few bcl-2 rearranged B cells in HIV FLH, at almost the same level as that in non-HIV-related FLH. The usual absence of bcl-2 rearrangement in the HIV-associated B-cell lymphomas suggests that the bcl-2 oncogene in the rearranged B cells of FLH is not cooperating with other oncogenes during HIV lymphomagenesis.

VJ rearrangements of the TCR gamma locus in peripheral T-cell lymphomas: analysis by polymerase chain reaction and denaturing gradient gel electrophoresis.

Using Southern blotting for the diagnosis of clonality in peripheral T-cell lymphomas (PTCLs), analysis of the T-cell receptor (TCR) gamma gene rearrangement was shown to be more informative than that of the TCR beta gene rearrangement. In order to amplify every VJ gamma rearrangement, a polymerase chain reaction (PCR) procedure using newly designed GC-clamp primers has been developed. All primers can be mixed in a single multiplex PCR. PCR products are analysed by denaturing gradient gel electrophoresis (DGGE), providing tumour-specific imprints inasmuch as the procedure characterizes N sequence polymorphism at the VJ junctions. In a series of 30 PTCL cases, the PCR procedure demonstrated 27 cases to be clonally rearranged and failed in three cases. PCR was more accurate than Southern blotting, showing 47 rearranged gamma alleles, four of which were undetectable on the Southern blot. When lymphomas were studied at different sites and at relapse, the DGGE pattern remained unchanged. In PTCL, the proposed PCR is helpful for the diagnosis and staging of the disease and should improve the follow-up monitoring. The undetectability of clonal rearrangements in a few cases is discussed in the light of concepts of lymphomagenesis and T-cell differentiation.

[Pseudo-myelomatous plasmacytosis of the bone marrow in a multicentric Castleman's disease]. / Plasmocytose médullaire pseudo-myélomateuse au cours d'une maladie de Castleman multicentrique. A propos d'une observation.

The authors report the case of a 35 year-old polynesian male admitted to hospital with a diagnosis of myeloma. Bone marrow study showed an intense plasmocytosis, mature, Marshalko type. A new physical examination disclosed polyadenopathies and the lymph node biopsy showed lymph node modifications typical of plasma cell type Castleman's disease. At the same time, the polytypic profile of the bone marrow plasmacytosis and of the hypergammaglobulinemia was demonstrated, thus confirming the reactive state of the plasmacytosis, due to Castleman's disease. Such massive, reactive plasmacytosis belong to one of the various pathological features of multicentric Castleman's disease. Thus, this disease should belong to the etiologic diagnosis of intense bone marrow plasmacytosis and be distinguished from multiple myeloma, sometimes associated to Castleman's disease, especially in case of POEMS syndrome.

Cutaneous T-cell infiltrates: analysis of T-cell receptor gamma gene rearrangement by polymerase chain reaction and denaturing gradient gel electrophoresis.

In cutaneous T-cell infiltrates, the demonstration of a clonal T-cell receptor (TCR) gene rearrangement has been considered helpful to distinguish Cutaneous T-cell lymphomas from reactive lymphoproliferation. Hence, a polymerase chain reaction (PCR) method using GC-clamp primers and denaturing gradient gel electrophoresis has been developed in our laboratory to analyze the TCR gamma locus configuration. Two hundred eleven cutaneous samples from 155 patients were analyzed. A detectable clonal TCR gamma rearrangement was significantly associated with cutaneous T-cell lymphomas as defined by morphologic and immunologic criteria. A clonal TCR gamma rearrangement was also detected frequently in lymphomatoid papulosis, never in reactive lymphocytic infiltrates and B-cell lymphomas, and rarely in parapsoriasis en plaque and cutaneous lymphoid hyperplasia. Forty five patients had both a cutaneous and a peripheral blood sample. Fifteen had a detectable clonal rearrangement in the two samples and 22 were negative. Six patients had a positive skin sample and a negative blood sample, whereas two patients had a positive blood sample and a negative skin sample. Four lymph node samples were analyzed and the PCR results were the same as in the skin. Finally, 21 patients had sequential samples of recurrent skin lesions. The PCR results were concordant in all and, when detectable, the clonal TCR gamma rearrangement remained unchanged in a given patient. Because of its simplicity and accuracy, the newly designed PCR procedure improves the monitoring of diagnosis, staging, and follow-up in cutaneous T-cell infiltrates.

Lymph node involvement revealing a lymphomatous polyposis of the gastrointestinal tract.

The digestive tract is the most frequent site of extranodal malignant lymphomas. Lymphomatous polyposis is one of them, and its prognosis is poor. It corresponds to a digestive localization of mantle cell lymphoma. In most cases it is discovered following digestive symptoms. However, in some cases this digestive malignant lymphoma may be asymptomatic. Thus complete endoscopic exploration of the digestive tract including biopsies is necessary for every patient presented with lymph node mantle cell lymphoma.

Recombination pattern of the TCR gamma locus in human peripheral T-cell lymphomas.

The recombination events of the gamma and beta T-cell receptor (TCR) loci were analysed in a series of 39 peripheral T-cell lymphomas (PTCLs) in association with the expression of TCR chains. In TCR alpha beta PTCLs, 22/23 cases showed a gamma-gene rearrangement while only 18/23 showed a concomitant beta-gene rearrangement. The germline configuration of the beta locus was found in angiommunoblastic lymphadenopathy and lymphoepithelioid lymphomas. Three gamma delta PTCLs rearranged both gamma and beta genes. TCR silent PTCLs showed three different patterns of gamma- and beta-gene rearrangements. Three cases were in germline configuration for both loci; five cases had a rearranged gamma and a germline beta locus; and five cases had the two loci rearranged. Regarding the variable genes in the gamma-rearranged alleles, members of the V gamma I subgroup were the most frequently presented (39/50), followed by V gamma II, V gamma III, and V gamma IV (9/50, 1/50, and 1/50, respectively). Joining segment usage was as follows: J1 or J2 (32/50), JP1 or JP2 (17/50), and JP (1/50). Taken together, these data demonstrate that the gamma locus is more frequently rearranged whatever the TCR expression. The gamma-locus analysis provides a better diagnostic yield than the beta locus in the study of PTCL clonality.

Prognostic value of chromosomal abnormalities in follicular lymphoma.

The t(14;18)(q32;q21) chromosomal translocation is observed in more than 75% of cases of follicular lymphoma. Several additional chromosomal abnormalities, which might contribute to tumor progression, have also been described. However, prognostic implications of cytogenetic features in follicular lymphoma have not been clearly established. In an attempt to correlate cytogenetic findings with clinical outcome, we have studied survival and risk of transformation into a more aggressive lymphoma in 66 follicular lymphoma patients from whom a lymph node had been karyotyped at the time of diagnosis. A t(14;18) was the most common abnormality, having been observed in 51 patients (77%), but this showed no correlation with clinical outcome. Seventeen other recurrent numerical or structural abnormalities were identified in more than 10% of the patients. A high percentage of cells (> or = 90%) with abnormal metaphases and a number of chromosomal breaks higher than 6 were associated with a poor survival (P > .01 each). Patients with an abnormality of chromosome region 1p21-22 (P < .01), of 6q23-26 (P < .001), or of the short arm of chromosome 17 (P < .001) had a significantly shorter survival in univariate analysis. Multivariate analysis identified a break at 6q23-26 (P = .01) and 17p (P = .01) as independent prognostic factors in this population. The risk of transformation into a diffuse large-cell lymphoma was significantly higher in patients with either a 6q23-26 (P < .001) or a 17p (P < .01) abnormality. Chromosomal analysis of follicular lymphoma at the time of diagnosis can thus provide important information about the risk of transformation and survival.(ABSTRACT TRUNCATED AT 250 WORDS)