Prognostic value of baseline total metabolic tumor volume (TMTV0) measured on FDG-PET/CT in patients with peripheral T-cell lymphoma (PTCL).

BACKGROUND: Most peripheral T-cell lymphoma (PTCL) patients have a poor outcome and the identification of prognostic factors at diagnosis is needed. PATIENTS AND METHODS: The prognostic impact of total metabolic tumor volume (TMTV0), measured on baseline [(18)F]2-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography, was evaluated in a retrospective study including 108 PTCL patients (27 PTCL not otherwise specified, 43 angioimmunoblastic T-cell lymphomas and 38 anaplastic large-cell lymphomas). All received anthracycline-based chemotherapy. TMTV0 was computed with the 41% maximum standardized uptake value threshold method and an optimal cut-off point for binary outcomes was determined and compared with others prognostic factors. RESULTS: With a median follow-up of 23 months, 2-year progression-free survival (PFS) was 49% and 2-year overall survival (OS) was 67%. High TMTV0 was significantly associated with a worse prognosis. At 2 years, PFS was 26% in patients with a high TMTV0 (>230 cm(3), n = 53) versus 71% for those with a low TMTV0, [P < 0.0001, hazard ratio (HR) = 4], whereas OS was 50% versus 80%, respectively, (P = 0.0005, HR = 3.1). In multivariate analysis, TMTV0 was the only significant independent parameter for both PFS and OS. TMTV0, combined with PIT, discriminated even better than TMTV0 alone, patients with an adverse outcome (TMTV0 >230 cm(3) and PIT >1, n = 33,) from those with good prognosis (TMTV0 ≤230 cm(3) and PIT ≤1, n = 40): 19% versus 73% 2-year PFS (P < 0.0001) and 43% versus 81% 2-year OS, respectively (P = 0.0002). Thirty-one patients (other TMTV0-PIT combinations) had an intermediate outcome, 50% 2-year PFS and 68% 2-year OS. CONCLUSION: TMTV0 appears as an independent predictor of PTCL outcome. Combined with PIT, it could identify different risk categories at diagnosis and warrants further validation as a prognostic marker.

Breast implant-associated anaplastic large cell lymphoma: two distinct clinicopathological variants with different outcomes.

BACKGROUND: ALK-negative anaplastic large cell lymphoma associated with breast implant (i-ALCL) has been recently recognized as a distinct entity. Among 43 830 lymphomas registered in the French Lymphopath network since 2010, 300 breast lymphomas comprising 25 peripheral T-cell lymphomas (PTCL) were reviewed. Among PTCL, ALK-negative ALCL was the most frequent and all of them were associated with breast implants. PATIENTS AND METHODS: Since 2010, all i-ALCL cases were collected from different institutions through Lymphopath. Immuno-morphologic features, molecular data and clinical outcome of 19 i-ALCLs have been retrospectively analyzed. RESULTS: The median age of the patients was 61 years and the median length between breast implant and i-ALCL was 9 years. Most implants were silicone-filled and textured. Implant removal was performed in 17 out of 19 patients with additional treatment based on mostly CHOP or CHOP-like chemotherapy regimens (n = 10/19) or irradiation (n = 1/19). CHOP alone or ABVD following radiation without implant removal have been given in two patients. The two clinical presentations, i.e. effusion and less frequently tumor mass correlated with distinct histopathologic features: in situ i-ALCL (anaplastic cell proliferation confined to the fibrous capsule) and infiltrative i-ALCL (pleomorphic cells massively infiltrating adjacent tissue with eosinophils and sometimes Reed-Sternberg-like cells mimicking Hodgkin lymphoma). Malignant cells were CD30-positive, showed a variable staining for EMA and were ALK negative. Most cases had a cytotoxic T-cell immunophenotype with variable T-cell antigen loss and pSTAT3 nuclear expression. T-cell receptor genes were clonally rearranged in 13 out of 13 tested cases. After 18 months of median follow-up, the 2-year overall survival for in situ and infiltrative i-ALCL was 100% and 52.5%, respectively. CONCLUSIONS: In situ i-ALCLs have an indolent clinical course and generally remain free of disease after implant removal. However, infiltrative i-ALCLs could have a more aggressive clinical course that might require additional therapy to implant removal.

[Giant cell arteritis: guidelines of the University Hospital of Lausanne]. / Artérite de Horton: recommandations Lausannoises de prise en charge.

Giant cell arteritis (GCA) is a subacute/chronic vasculitis and represents the most common form of systemic vasculitis in people over the age of 50 years. The absence of clear and specific diagnostic criteria with the highly variable clinical presentation is a diagnostic challenge requesting a multidisciplinary approach. Yet, GCA is an emergency and the treatment must be initiated very rapidly due to the risk of blindness. This article presents a review of GCA as well as the diagnostic and therapeutic institutional guidelines of the University Hospital of Lausanne.

Real-world EGFR testing practices for non-small-cell lung cancer by thoracic pathology laboratories across Europe.

BACKGROUND: Testing for epidermal growth factor receptor (EGFR) mutations is an essential recommendation in guidelines for metastatic non-squamous non-small-cell lung cancer, and is considered mandatory in European countries. However, in practice, challenges are often faced when carrying out routine biomarker testing, including access to testing, inadequate tissue samples and long turnaround times (TATs). MATERIALS AND METHODS: To evaluate the real-world EGFR testing practices of European pathology laboratories, an online survey was set up and validated by the Pulmonary Pathology Working Group of the European Society of Pathology and distributed to 64 expert testing laboratories. The retrospective survey focussed on laboratory organisation and daily EGFR testing practice of pathologists and molecular biologists between 2018 and 2021. RESULTS: TATs varied greatly both between and within countries. These discrepancies may be partly due to reflex testing practices, as 20.8% of laboratories carried out EGFR testing only at the request of the clinician. Many laboratories across Europe still favour single-test sequencing as a primary method of EGFR mutation identification; 32.7% indicated that they only used targeted techniques and 45.1% used single-gene testing followed by next-generation sequencing (NGS), depending on the case. Reported testing rates were consistent over time with no significant decrease in the number of EGFR tests carried out in 2020, despite the increased pressure faced by testing facilities during the COVID-19 pandemic. ISO 15189 accreditation was reported by 42.0% of molecular biology laboratories for single-test sequencing, and by 42.3% for NGS. 92.5% of laboratories indicated they regularly participate in an external quality assessment scheme. CONCLUSIONS: These results highlight the strong heterogeneity of EGFR testing that still occurs within thoracic pathology and molecular biology laboratories across Europe. Even among expert testing facilities there is variability in testing capabilities, TAT, reflex testing practice and laboratory accreditation, stressing the need to harmonise reimbursement technologies and decision-making algorithms in Europe.

Diffuse large B-cell lymphoma of Waldeyer's ring has distinct clinicopathologic features: a GELA study.

BACKGROUND: Diffuse large B-cell lymphomas (DLBCLs) arising in specific extranodal sites have peculiar clinicopathologic features. PATIENTS AND METHODS: We analyzed a cohort of 187 primary Waldeyer's ring (WR) DLBCLs retrieved from GELA protocols using anthracyclin-based polychemotherapy. RESULTS: Most patients (92%) had stage I-II disease. A germinal center B-cell-like (GCB) immunophenotype was observed in 61%, and BCL2 expression in 55%, of WR DLBCLs. BCL2, BCL6, IRF4 and MYC breakpoints were observed in, respectively, 3 of 42 (7%), 9 of 36 (25%), 2 of 26 (8%) and 4 of 40 (10%) contributive cases. A variable follicular pattern was evidenced in 30 of 68 (44%) large biopsy specimens. The 5-year progression-free survival (PFS) and the overall survival (OS) of 153 WR DLBCL patients with survival information were 69.5% and 77.8%, respectively. The GCB immunophenotype correlated with a better OS (P = 0.0015), while BCL2 expression predicted a worse OS (P = 0.037), an effect overcome by the GCB/non-GCB classification. Compared with matched nodal DLBCLs, WR DLBCLs with no age-adjusted international prognostic index factor disclosed a better 5-year PFS rate (77.5% versus 70.7%; P = 0.03). CONCLUSIONS: WR DLBCLs display distinct clinicopathologic features compared with conventional DLBCLs, with usual localized-stage disease, common follicular features and a high frequency of GCB immunophenotype contrasting with a low rate of BCL2 rearrangements. In addition, they seem to be associated with a better outcome than their nodal counterpart.

Surgical treatment of cardiovascular complications in patients with Marfan syndrome: a report of two cases and literature review.

Cardiovascular disease is the main cause of morbidity and mortality in patients with Marfan syndrome. The most life threatening complication is aortic root aneurysms leading to aortic dissection or rupture. It can be prevented by regular aortic follow-up and prophylactic aortic surgery. Modern aortic surgery has led to a substantial increase in the life expectancy of these patients. We report two cases of Marfan syndrome with cardiovascular complications. Their management is discussed according to the most recent literature.

Cardiac paraganglioma: diagnostic work up and review of the literature.

Paraganglioma of the heart are potentially invasive, highly vascularized tumors for which complete resection may be curative. Derived from the cardiac wall in most instances, resectability can be assessed after integration of the data provided by MRI in T2 sequence, and coronarography. A fully documented case of a large cardiac pheochromocytoma of the left atrium and AV groove is reported and the pertinent literature on the subject is here presented.

[Clinical case of the month. Intrapulmonary lung sequestration diagnosed in an adult]. / Le cas clinique du mois. A propos d'un cas de séquestration pulmonaire intralobaire diagnostiqué à l'âge adulte.

Pulmonary sequestration is a rare congenital lung malformation characterized by an abnormal segment of bronchopulmonary tissue supplied by aberrant systemic arteries. Due to the non-specific symptomatology, the diagnosis can be missed. Imaging is the cornerstone of the diagnosis. Complete surgical resection provides the definitive treatment. We report a case of pulmonary sequestration associated with an asymptomatic aspergillosis presenting during adulthood and describe briefly the epidemiology, embryology, histology, imaging and surgical treatment of this congenital abnormality.

[Hard palate B cell lymphoma with spontaneous regression]. / Régression spontanée d'un lymphome B à grandes cellules du palais.

INTRODUCTION: Non-Hodgkin lymphomas are common cancers that can develop in the upper aero-digestive tract. We describe a case of a large B-cell palatine lymphoma with spontaneous clinical regression. CASE: A 58-year-old female patient presented with a sub-mucosal lesion of the hard palate. CT scan and magnetic resonance imaging revealed a lesion invading the right posterior palatine canal. At the second consultation, 15 days after performing the biopsy, the lesion had disappeared. PET scan proved the absence of lesion. Lymph node biopsy supported the diagnosis of large B-cell lymphoma. DISCUSSION: Large B-cell lymphoma of the hard palate is a rare disease. Only 27 cases have been described in the international literature. The anatomopathological analysis is often difficult to perform. The final diagnosis is often made by immunochemistry. The usual treatment is R-CHOP chemotherapy (cyclophosphamide, adriamycin, vincristine, prednisone combined to rituximab) with a 5-year survival rate at 55%.

Clinical and molecular practice of European thoracic pathology laboratories during the COVID-19 pandemic. The past and the near future.

BACKGROUND: This study evaluated the consequences in Europe of the COVID-19 outbreak on pathology laboratories orientated toward the diagnosis of thoracic diseases. MATERIALS AND METHODS: A survey was sent to 71 pathology laboratories from 21 European countries. The questionnaire requested information concerning the organization of biosafety, the clinical and molecular pathology, the biobanking, the workload, the associated research into COVID-19, and the organization of education and training during the COVID-19 crisis, from 15 March to 31 May 2020, compared with the same period in 2019. RESULTS: Questionnaires were returned from 53/71 (75%) laboratories from 18 European countries. The biosafety procedures were heterogeneous. The workload in clinical and molecular pathology decreased dramatically by 31% (range, 3%-55%) and 26% (range, 7%-62%), respectively. According to the professional category, between 28% and 41% of the staff members were not present in the laboratories but did teleworking. A total of 70% of the laboratories developed virtual meetings for the training of residents and junior pathologists. During the period of study, none of the staff members with confirmed COVID-19 became infected as a result of handling samples. CONCLUSIONS: The COVID-19 pandemic has had a strong impact on most of the European pathology laboratories included in this study. Urgent implementation of several changes to the organization of most of these laboratories, notably to better harmonize biosafety procedures, was noted at the onset of the pandemic and maintained in the event of a new wave of infection occurring in Europe.

[Organizing pneumonia: three case reports]. / Pneumopathies organisées: à propos de 3 cas.

Infiltrative lung lesions are not always linked to infectious processes or cancers. An interesting entity, the OP (Organizing Pneumonia) or COP (Cryptogenic Organizing Pneumonia)--formerly BOOP (Bronchiolitis Obliterans Organizing Pneumonia)--is discussed through observations repor. ted in this article. We provide some keys to allow the astute observer to target this often curable disease.

[Clinical case of the month. The "classic" triad presentation of mucinous bronchiolo-alveolar carcinoma]. / Le cas clinique du mois. La triade "classique" de présentation de certains cancers bronchiolo-alvéolaires mucineux.

The case of a 59-year-old female complaining of cough of recent onset, abundant salty expectoration and lung condensation is presented. This "triad" constitutes a rare but nearly pathognomonic presentation of mucinous bronchioloalveolar carcinoma (BAC) of the lung.

Pulmonary veno-occlusive disease in myeloproliferative disorder.

The present study reports a case of biopsy-proven pulmonary veno-occlusive disease as a cause of severe pulmonary hypertension in a patient suffering from a chronic myeloproliferative disorder. The pulmonary disease evolved favourably under treatment with defibrotide, a pro-fibrinolytic medication used in hepatic veno-occlusive disease.

[Current treatment of follicular lymphoma]. / Traitements actuels du lymphome folliculaire.

After diffuse large B-cell lymphoma, follicular lymphoma is the most frequent non-Hodgkin's lymphoma. It remains incurable, except for localized diseases. Advanced disease has to be treated only in the presence of clinical and/or biology aggressiveness. These patients should be treated by rituximab (Mab-Thera) associated to polychemotherapy comprising cyclophosphamide, vincristine and prednisone. After this therapy, the benefit of rituximab in maintenance has to be confirmed. Autologous stem cell transplantation is now reserved for young patients in first relapse. Allogenic stem cell transplantation is also an interesting option. The other therapeutic options comprise radio-immunotherapy with 90Y ibritumomab tiuxetan (Zevalin) and bortezomib (Velcade).

Chronic hepatitis C infection in a patient with bone marrow hypoplasia.

Chronic hepatitis C virus (HCV) infection is associated with multifarious extra-hepatic manifestations; the most described and discussed being mixed cryoglobulinemia which is strongly related to B-cell lymphoproliferative disorders (LPDs). We present a case of chronic HCV infection and mixed cryoglobulinemia, with minimal liver involvement. The case is a 53-year-old patient who was diagnosed as having bone marrow hypoplasia at the age of three. She received several blood transfusions to normalize her haemoglobin. At the age of 31, she was diagnosed with rheumatoid arthritis on account of her diffuse joint pain and inflammation, elevated rheumatoid factor (RF) and Raynaud's phenomenon. Twenty years later, monoclonal gammopathy of IgG Lambda (one year later, changed to IgM Kappa) was detected during a routine examination. A bone marrow biopsy showed hypoplasia, Kappa positive B-lymphocytes and low-grade malignant lymphoma cells. PCR of the bone marrow aspirate was not contributory. No treatment was initiated owing to her poor bone marrow function and she is under regular follow-up.

Adrenal ganglioneuroma. A neoplasia to exclude in patients with adrenal incidentaloma.

OBJECTIVE: To determinate the MRI and CT scanning appearance of adrenal ganglioneuroma and correlate the imaging with histological features. SUMMARY BACKGROUND DATA: In the last 10 years, eight patients with a pathologically proven adrenal ganglioneuroma were operated on in our department of endocrine surgery. To our knowledge, these patients represent one the largest reported cohorts of adrenal ganglioneuroma treated in a single institution. METHODS: All these eight patients had a comprehensive hormonal work up and underwent CT and/or MRI. Biological data, radiological features and histological findings were thoroughly reviewed in order to further characterize these tumours. RESULTS: The most relevant characteristics of adrenal GN resected in our patients were: No hormonal hypersecretion, Presence of calcifications; no vessel involvement; and a non-enhanced attenuation of less than 40 HU on CT, A low non-enhanced T1W signal, a slightly high and heterogeneous T2W signal, a late and gradual enhancement on dynamic MRI, especially if associated with a whorled pattern. CONCLUSIONS: Even if many aggressive tumours, mainly adrenal carcinoma, may share some of these radiological features, the presence of all or most of them must made the clinician evoke the diagnosis of GN.

[Anatomo-clinical comparison: caecal duplication cyst]. / Confrontation anatomo-clinique: duplication caecale.

Enteric duplication cysts, and particularly caecal duplication cysts, are rare and generally benign congenital anomalies for which a diagnosis is difficult to make because they mimic other surgical diseases. A surgical management is the treatment of choice. The diagnosis can then be made or confirmed by histopathologic analysis.

[Isolated tricuspid valve endocarditis as a cause of fever of unknown origin]. / Endocardite infectieuse tricuspidienne comme cause d'une fièevre d'origine indéterminée.

Isolated tricuspid valve endocarditis is the least common endocarditis with an incidence of 5 to 10% in the literature. It is usually described in drug abusers and as a complication of nosocomial infections (catheter, post-surgery...). We present the case of a 70 year-old patient admitted for a fever of unknown origin lasting for 2 months. He had an isolated tricuspid endocarditis with Enterococcus faecalis. We review the diagnostic criterias predisposing factors and treatment of right-sided valvular endocarditis, particularly the endocarditis produced by Enterococcus faecalis, a rare etiopathogenic agent of tricuspid endocarditis.