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.

[Endocrine tumor arising in heterotopic gastric pancreas]. / Tumeur endocrine développée sur pancréas ectopique gastrique.

We report the case of a 49-year-old caucasian woman, in whom an endocrine tumor arising in gastric heterotopic pancreas was diagnosed. The patient was treated surgically with a gastric wedge resection. Heterotopic pancreas is a benign anatomic condition, probably widely underdiagnosed because usually asymptomatic. The malignant transformation of aberrant pancreas is very rare and almost always in adenocarcinoma. The endocrine tumors developed in heterotopic pancreas are exceedingly rare. Of our knowledge, only four cases have been published and only one case in the gastric location similar to this reported case.

[Non-Hodgkin's malignant lymphoma of the peripheral nervous system: clinicopathological correlations in ten patients]. / Lymphomes malins non Hodgkiniens du système nerveux périphérique. Corrélations anatomo-cliniques dans 10 observations.

INTRODUCTION: Identifying tumor infiltration or compression in patients with non-Hodgkin's malignant lymphoma presenting peripheral neuropathy can be a difficult task. METHODS: We collected a series of patients with peripheral neuropathy with demonstrated lymphomatous infiltration or compression managed between October 1977 and October 2001 to search for clinico-pathological correlations. RESULTS: Ten cases were reviewed. Neurological manifestations were the inaugural symptom of the disease in 7 patients. Clinical presentations included 5 focal (3 cranial nerve palsies, 2 brachial radiculopathies) and 5 diffuse neuropathies (3 polyradiculoneuropathies, 1 polyneuropathy and 1 mononeuritis multiplex). The mechanisms of peripheral nerve involvement were classified into lymphomatous meningoradiculitis (5 cases), involvement of cranial nerves or spinal roots in their extraneuraxial course (3 cases) and infiltration of distal peripheral nerves (2 cases). Four long lasting survivals after treatment were observed. CONCLUSIONS: Prognosis depends much more on the haematological disease than on the neurological symptoms or tumor location.

Further demonstration of the diversity of chromosomal changes involving 2p23 in ALK-positive lymphoma: 2 cases expressing ALK kinase fused to CLTCL (clathrin chain polypeptide-like).

Anaplastic lymphoma kinase (ALK)-positive lymphomas are characterized by expression of a hybrid protein, comprising the cytoplasmic portion of the ALK tyrosine kinase fused to a partner protein. This hybrid kinase is often encoded by the nucleophosmin (NPM) NPM-ALK fusion gene resulting from the (2;5)(p23;q35) chromosomal translocation. However, the ALK gene at 2p23 may also be involved in 2 variant translocations, namely t(1;2)(q25;p23) and t(2;3)(p23;q21), which create the TPM3-ALK and TFG-ALK fusion genes, respectively. We report here 2 lymphomas with an unusual finely granular cytoplasmic ALK staining pattern, clearly different from the pattern observed in ALK-positive lymphomas carrying NPM-ALK or its variants. A cloned complementary DNA sequence from 1 of these 2 lymphomas contained the ALK gene fused to the second clathrin heavy chain gene (also referred to as clathrin heavy polypeptide-like gene) (CLTCL). The distinctive granular cytoplasmic staining pattern for ALK was likely to be due to binding of the fusion protein to clathrin-coated vesicles. The CLTCL gene is constitutively expressed in lymphoid cells and therefore presumably contributes an active promoter for the CLTCL-ALK gene. The fusion protein had a molecular weight (250 kd) that differs from all known ALK products, and it was autophosphorylated in an in vitro kinase assay, confirming that it is constitutively active and hence capable of contributing to malignant transformation. These 2 cases, therefore, represent a hitherto undescribed mechanism of ALK activation in lymphoma and further illustrate the diversity of fusion partners for the ALK gene.

MBR rearrangement and P-glycoprotein expression are not independent prognostic factors like p53 protein in malignant lymphoma.

Non-Hodgkin's lymphomas (NHL) are B-cell malignancies which generally present molecular abnormalities, such as bcl-2 translocation t(14; 18) predominantly in the follicular subgroup. Other molecular events have been described in NHL, including p53 gene mutation and overexpression of one chemoresistance mechanism, the multidrug resistance system, P-glycoprotein (MDR 1/P-gp). In this study, we analysed samples from 44 NHL patients with the presence of the bcl-2 major breakpoint region (MBR) rearrangement in 29 and without in 15. Immunochemical analysis revealed that 39 samples were positive for bcl-2 protein expression in tumoral cells (88.6%). Seventeen (38.6%) patients expressed P-gp and 9 (20.5%) expressed p53 proteins. Eleven patients expressed both bcl-2 and P-gp proteins, four expressed bcl-2 and p53 proteins whereas four expressed bcl-2, p53 and P-gp proteins. Our results confirm the importance of p53 expression as a key prognostic factor, and no objective response (OR) was found in patients with p53 positivity. MBR rearrangement was not associated with poor response to chemotherapy (62.1% OR in MBR positive patients v. 60% OR in MBR negative patients). The clinical impact of P-gp cannot be identified because no relationship was observed between P-gp expression and prognosis (58.8% OR in P-gp positive patients v. 63% OR in P-gp negative patients).

Primary mediastinal B-cell lymphoma: update of its clinicopathologic features.

The peculiar clinical, histomorphological and biological characteristics of PMBCL are reviewed. Special emphasis is given to the frequent aggressive clinical behaviour of this lymphoma in which conventional prognostic factors seem inadequate to identify high risk cases. The need for new clinical and/or biological prognostic markers is stressed.

CD23 antigen density is related to serum gamma globulin level, bone marrow reticulin pattern, and treatment in B chronic lymphocytic leukemia.

The CD23 antigen density was evaluated by a cytofluorometric technique in 55 patients with chronic lymphocytic leukemia. The quantification method was based on the use of biological standards in indirect immunofluorescence. The CD23 antigen density was correlated with the percentage of CD23 positive cells, but antigen density appeared to be a more informative parameter. CD23 antigen density was lower in stage B than in stages A or C patients, and higher in patients undergoing chemotherapy or previously treated than in untreated patients. There was a significant negative correlation between CD23 antigen density and serum gamma globulin and IgG levels, that existed only in patients in an advanced stage of the disease. CD23 antigen density was higher in patients with abnormal bone marrow reticulin pattern. Serum gamma globulin level was lower in these patients, as well as in patients with prognostically unfavorable histologic bone marrow infiltration pattern. These data emphasize the interest of antigen density as an additional parameter and the complex relationship between CD23 expression, hypogammaglobulinemia, bone marrow histologic findings, and treatment in chronic lymphocytic leukemia.

An alpha-spectrin mutation responsible for hereditary elliptocytosis associated in cis with the alpha v/41 polymorphism.

The alpha 207 Leu-->Pro mutation in spectrin has recently been identified as a cause of alpha I/50-46a hereditary elliptocytosis (HE) or pyropoikilocytosis among Black people. We have found this mutation in a Moroccan family in both the heterozygous and homozygous states. The mutated alpha-spectrin allele carried, in cis, the alpha V/41 polymorphism, a common polymorphism altering the peptide maps and associated with a low-expression level. This is the first report of the cis combination of an HE mutation and the alpha V/41 polymorphism. Presumably, such a combination accounts for the very low expression of the abnormal allele in the heterozygous state.

A study of 15 cases of primary mediastinal lymphoma of B-cell type.

Fifteen cases of pure supradiapragmatic lymphoma with initial prominent antero-superior mediastinal involvement displaying a B-cell pattern of reactivity were studied. These cases occurred in six men and nine women with a median age of 33 years at diagnosis (range, 23 to 75 years). Supradiapragmatic peripheral lymphadenopathies were present in three cases, and intrathoracic extension to the lung, pericardium, or pleura was possible. In five cases a thymic origin was obvious. All cases exhibited a B-cell pattern of differentiation, with a great variety of histopathologic aspects associated with a high frequency of fibrosis and/or necrosis. Hodgkin's disease was initially misdiagnosed in four cases. The evolution was purely local, with extrathoracic extension in five cases, at the ultimate phase of the disease. The prognosis appeared to be poor with only five patients still alive at a median survival time of 16 months. A complete chemoresistance and radio-resistance was observed in seven cases; only two complete remissions were achieved with aggressive chemotherapy. Prolonged remission could be achieved after surgical reduction of the mass. Primary B-cell mediastinal lymphoma appears to be a distinct clinical entity with local evolution and resistance to therapy. A new therapeutic regimen, which could include surgery in some cases, should be found for this disease.

Interest of simultaneous ultrastructural characterization of morphology, cytochemistry and immune phenotype in a case of putative hybrid acute leukaemia.

A case of acute leukaemia is reported in which blast cells expressed some B-related antigens (namely the CALLA antigen) and no peroxidase activity at the optical level; however, some mature granular cells contained Auer rods. Simultaneous characterization of ultrastructural morphology, cytochemistry and immune phenotype was performed. There was an apparent mutual exclusion in the expression of myeloperoxidase activity and the CALLA antigen, and a heterogeneity in the CALLA expression among the blastic population. These results disagree with the hypothesis of a true biphenotypic leukaemia and demonstrate a complete heterogeneity between the lymphoblastoid cells and the myeloid ones. The interest of such a simple combined method in a case of putative hybrid acute leukaemia is emphasized.