Mediastinum

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F de 36 ans, asymptomatique, se présente pour une masse médiastinale antérieure, radiologiquement (masse prenant le contraste de manière hétérogène, de 7.7 cm) en faveur d'une tumeur thymique. Pas d'adenopathie médiastinale observée.

Biopsie (hors HDF) en faveur d'un thymome.

Resection chirurgicale (HDF)

Macroscopiquement, la masse est bilobée de 10x7.5cm. Un lobe quasi-entièrement kystique à contenu brunâtre, et l'autre charnue, microkystique, à contenu séreux.

 

36 yo female, no symptoms, discovered an anterior mediastinal mass, on radiology (heterogenously enhancing mass, mesuring 7.7 cm) in favour of a thymic tumour. No enlarged mediastinal, axillary or hilar lymph nodes.

Biopsy (out HDF) in favor of a thymoma.

Surgical resection (HDF)

Grossly, the mass was bilobated mesuring 10x7.5cm. One lobe was cystic, with a brownish content. The second was fleshy, microcystic, with serous content.

 
     
     
     
     
     
     
     
       
     
  CK (AE1-AE3)   CK (AE1-AE3)  
     
  CK (AE1-AE3)   CK (AE1-AE3)  
     
  CK (AE1-AE3)   CK (AE1-AE3)  
     
  CD5   CD5  
       
  CD5      
     
  CD20   CD20  
     
  CD20   CD20  
     
  CD30   CD23  
 

Diagnostic proposé

 

 

 

 

 

 

 

Lymphome médiastinal, à grandes cellules B, thymique sur kyste thymique.

 

Proposed diagnosis

 

 

 

 

 

 

 

Mediastinal (thymic) large B cell lymphoma on a thymic cyst.

 
  Arguments   Clues  
 
 
 
  Reference: Rosai and Ackerman's Surgical Pathology. 10th Ed.  
 

Large cell lymphoma

Mediastinal large cell lymphoma can present as a mass in the thymus with or without lymph node involvement. Most patients are young adult females, and presentation with superior vena caval syndrome is frequent. The tumor has grossly invasive features: extension into pericardium, pleura, lung, sternum, and chest wall is common.The consistency is generally firm, and there are frequent foci of necrosis. Microscopically, a sometimes striking feature is the presence of wide bands of fibrosis, which results in compartmentalization of the tumor cells and a microscopic appearance that simulates an epithelial, germ cell, or neuroendocrine neoplasm. Other reasons for the frequent misdiagnosis of this tumor include the following: perivascular collections of lymphocytes (which may be misinterpreted as the perivascular spaces of thymoma); artifactual clearing of the cytoplasm induced by formalin fixation (not present in B5 or Zenker's fixed material) simulating seminoma; presence of a large number of reactive T cells; rosette-like formations;and entrapment of thymic epithelium.The last feature can also create problems when the tumor is examined ultrastructurally or when immunostained for keratin. Parenthetically, another immunohistochemical pitfall is represented by lysozyme and other histiocytic markers, in the sense that the sometimes abundant reactive histiocytic population may lead to a mistaken diagnosis of true histiocytic sarcoma.

 
 

A diagnosis of large cell lymphoma should be favored in the presence of tumor cells with large, vesicular, irregularly shaped nuclei (indented, kidney-shaped, polylobated); entrapment of intrathymic and perithymic fat; invasion of blood vessel wall, pleura, or lung; and the fact that the fibrosis is manifested not only in the form of wide hyaline bands but also as a fine network that entraps individual cells. In some cases, the cellular pleomorphism is extreme. Exceptionally, the tumor cells show tropism for germinal centers. The diagnosis may also be suspected on the basis of fine needle aspiration material. Immunohistochemical reactivity for CD45 is invariably found. The large majority of the tumors are of B-cell nature (mediastinal large B-cell lymphoma), but T-cell malignancies are also represented. Close to 70% of the cases also express CD30. A diagnostically helpful marker is CD23, which is expressed in 70% of cases of mediastinal large B-cell lymphoma, but in less than 15% of large B-cell lymphomas of other sites. They have also been found to express BCL6 and CD10, suggesting a derivation from germinal center cells. The peculiar morphologic, immunohistochemical, and molecular attributes of mediastinal large B-cell lymphoma are significantly different from those of large B-cell lymphoma at other sites. It has been postulated that it represents a distinct type of lymphoma, possibly arising from a subset of intrathymic lymphoid cells (‘asteroid B-cells’), and that MAL (an integral membrane protein located in glycolipid-enriched membrane microdomains, called lipid rafts) is a distinct molecular marker for this tumor. In contrast to conventional diffuse large B-cell lymphoma, mediastinal large B-cell lymphoma rarely exhibits BCL2 or BCL6 gene rearrangement. Common genetic changes are gains at 9p24 (includingJAK2PDL1, and PDL2 loci) and 2p15 (including REL and BCL11A loci). Inactivating mutations in SOCS1, an inhibitor of JAK/STAT signaling, occur in about half of the cases, and contribute to activation of STAT. In addition, the nuclear factor kappa B (NFκB) pathway is constitutively activated, but the pathogenetic mechanism remains unclear.

It should be kept in mind that in young females with a clinically and microscopically malignant mediastinal tumor in which the differential diagnosis is among malignant thymoma, seminoma (germinoma), and large cell malignant lymphoma, the correct diagnosis will be the latter entity in the large majority of cases.

Mediastinal large B-cell lymphoma is usually restricted to the intrathoracic region at the time of initial presentation. An excellent response to radiation therapy and chemotherapy is the rule, but in some instances the tumor recurs within the chest and spreads to other sites, including peripheral lymph nodes and central nervous system. The presence of pleural effusion at presentation is associated with poor outcome. We have been impressed by the high frequency with which the kidneys have been found to be involved in recurrent disease, and wonder whether some ‘homing’ mechanism is involved analogous to that hypothesized for mucosa-associated lymphoid tissue (MALT) lymphoma.