Primary mediastinal (thymic) large B cell lymphoma

Definition

Primary site of involvement must be mediastinum
- Other nodal and extranodal sites may be involved
Diffuse infiltration and sclerosis frequent
- Frequent diffuse infiltration of mediastinal soft tissue and surrounding structures
  - Overrun thymus may be identifiable
  - Thymic epithelium may be hyperplastic or cystic
- Sclerosis, necrosis and large vessel vascular invasion frequent
  - Primarily when extrathymic or extranodal
Wide range of nuclear features
- May be even more variable than usual diffuse large B cell lymphoma
- Cytoplasm variable but abundant and clear (retraction artifact) in about 40% of cases
- Cytology does not correlate with behavior
B lineage required
- Immunoglobulin frequently negative, even in frozen tissue or by flow, although immunoglobulin genes are rearranged

John P Higgins MD
Robert V Rouse MD
Department of Pathology
Stanford University School of Medicine
Stanford CA 94305-5342

Original posting:: March 8, 2005

B lineage is required for diagnosis

CD20 and or CD79a pos
Immunoglobulin frequently negative, even with frozen tissue or on flow, although immunoglobulin genes are rearranged

Immunoglobulin gene rearrangements are present, even in cases in which immunoglobulin is not demonstrable
Cytogenetics infrequently useful
- Gains of chromosomal material are more common than losses
- However, gain of chromosome 9p, seen in a minority of cases, is the only non-random karyotypic alteration

Nodular sclerosis Hodgkin lymphoma and mediastinal B cell lymphoma share features of age, location and sclerotic background and frequently have to be distinguished on the basis of small specimens
If the biopsy is large enough, the following features may be definitive for the diagnosis of NSHL
- Nodular architecture
- Polymorphous background
- Cytologic features of RS cells
Most specimens will need immunohistochemical study as below
- Note that in mediastinal B cell lymphoma, immunoglobulin staining is frequently negative, even in frozen tissue
- Note that Reed Sternberg cells are frequently positive for both kappa and lambda, apparently due to nonspecific uptake of serum immunoglobulin.

Sclerosis usually confined to thick bands and capsule
Thymic epithelial cells should be numerous
- Keratin stain may be useful to highlight epithelial cells
  - However, we have occasionally found thymoma epithelial cells to stain only variably with common anti-keratin antibodies
- Overrun or even hyperplastic thymic epithelial cells may be seen in lymphoma
- Even distribution is more typical of thymoma
Immature T cells are numerous in most thymomas
- CD1a, CD99 and TdT positive
CD20 may stain epithelial cells in Type A and Type AB thymomas
- Positive cells are spindled
- Keratin stains and other B lineage markers should resolve the diagnosis
Necrosis may be widespread in both thymoma and lymphoma

Keratin and CD20 should resolve the differential if lesional cells are present in specimen

Sclerosing mediastinitis lacks the population of large atypical B cells of mediastinal B cell lymphoma

Embryonal carcinoma and yolk sac tumor should be clearly keratin positive
- AFP and HCG may be positive, but frequently negative
Seminoma is frequently negative for keratin
- Look closely for punctate keratin staining
- PLAP is variably positive in seminoma, uniformly negative in lymphoma
- HCG may be positive if trophoblastic giant cells are present
Serum HCG or AFP may be positive in the absence of tissue section reactivity in germ cell tumors
B lineage markers and LCA should be negative in all germ cell tumors
Both embryonal carcinoma and mediastinal B cell lymphoma may be CD30 positive
One case of mediastinal lymphoma with HCG expression has been reported
Necrosis may be widespread in both germ cell tumors and lymphoma

Mean age 25-30 years but wide range
Female : Male 2:1
Frequent obstruction of superior vena cava or trachea
Frequent (26%) CNS involvement, primarily on relapse
Lamarre has suggested that there are two types of mediastinal B cell lymphoma
- Immunoglobulin negative, predominantly female, younger
- Immunoglobulin positive, no sex preference, older
The prognosis of primary mediastinal B cell lymphoma has been debated
- Some series have found aggressive clinical behavior and a poor prognosis
- Others indicate a similar prognosis to that of other non-mediastinal B cell lymphomas

Stage I
- I if involvement of a single lymph node region
- IE if involvement of a single extralymphatic organ or site
Stage II
- II if two or more lymph node regions on same side of diaphragm
- IIE if localized involvement of an extralymphatic organ or site and one or more lymph node regions on the same side of the diaphragm
Stage III
- III if Involvement of lymph node regions on both sides of the diphragm
- IIIS if spleen involved
- IIIE if extralymphatic site involved
Stage IV
- Diffuse or disseminated involvement of one or more extralymphatic organs or tissues, with or without associated lymph node involvement
Systemic Symptoms in 6 months preceding admission
- Fever, night sweats, 10% weight loss
- A = absent
- B = present
Extranodal sites are also designated
- M+ = marrow
- L+ = lung
- H+ = liver
- P+ = pleura
- O+ = bone
- D+ = skin and subcutaneous tissue
Although originally designed for Hodgkin lymphoma, the Ann Arbor System is also used for non-Hodgkin lymphomas.

Diagnosis in the World Health Organization (WHO) classification
- Equivalent diagnosis in other classifications used by relevant clinicians
Results of supplementary studies if performed
Relationship to other specimens from the same patient
Information relevant to staging if available

Warnke RA, Weiss LM, Chan JKC, Cleary ML, Dorfman RF . Tumors of the Lymph Nodes and Spleen, Atlas of Tumor Pathology, AFIP Third Series, Fascicle 14, 1995
Jaffe ES, Harris NL Stein H, Vardiman JW . Pathology and Genetics of Tumours of Haematopoietic and Lymphoid Tissues, World Health Organization Classification of Tumours 2001
Higgins JPT and Warnke RA. CD30 Expression Is Common in Mediastinal Large B-Cell Lymphoma. Am J Clin Pathol. 1999 Aug;112(2):241-7.
Cazals-Hatem D, Lepage E, Brice P, et al. Primary mediastinal large B-cell lymphoma. A clinicopathologic study of 141 cases compared with 916 nonmediastinal large B-cell lymphomas, a GELA ("Groupe d'Etude des Lymphomes de l'Adulte") study. Am J Surg Pathol. 1996;20: 877-888.

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© 2005 Stanford University School of Medicine