)
)
ANSWERS AND FINAL DIAGNOSIS:
Question #1: What is your diagnosis? Positive for malignant cells.
Question #2: Is this a primary or metastatic process (i.e. is this metastatic prostatic adenocarcinoma)? At this point, the specimen consists of abnormal large malignant appearing cells with increased nuclear to cytoplasmic ratio, pleomorphic nuclei, and numerous mitotic figures. Based on these morphologic findings, which includes large, irregular and discohesive cells with prominent nucleoli, places a neoplastic hematopoietic process high in the differential diagnosis. A poorly differentiated epithelial neoplasm or possibly a metastatic prostatic adenocarcinoma cannot be ruled out. The differential diagnosis includes a diffuse large B-cell lymphoma, anaplastic large cell lymphoma, and less likely metastatic poorly differentiated epithelial neoplasm.
Question #3: What do you tell the clinician? There is adequate material for the diagnosis; however, a second and third pass will be performed in order to obtain additional material for cellblock preparation.
In Table 1, the relevant immunohistochemical stains (Figures 5 and 6) that were performed are shown below. The immunohistochemical staining pattern of both diffuse large B-cell lymphoma and anaplastic large cell lymphoma are also listed.
|
Immunohistochemical Profile
|
||||
|
Antigen / Antibody |
Usual Reactivity |
Result |
Anaplastic large cell lymphoma |
Diffuse large B-cell lymphoma |
CD20* |
B-cells |
Large cells negative. |
NEGATIVE |
POSITIVE |
|
CD79a* |
B-cells |
Neoplastic cells negative |
NEGATIVE |
POSITIVE |
|
CD45/LCA* |
Leukocytes |
Large cells negative. |
+/- |
+/- |
|
CD15/LeuM1* |
Reed-Sternberg cells, myeloid |
Large cells negative. |
NEGATIVE |
NEGATIVE |
|
CD30* |
R-S cells, activated lymphocytes |
Large cells positive. |
POSITIVE |
NEGATIVE |
|
EMA* |
Epithelium, lymphocyte subset |
Some large cells positive. |
POSITIVE |
NEGATIVE |
|
Alk-1* |
Anaplastic large cell lymphoma kinase |
Moderate number of large cells positive. |
POSITIVE |
NEGATIVE (Rarely positive) |
|
CD3 |
T-cells |
Large cells negative |
NEGATIVE (>75%) |
NEGATIVE |
AE1/AE3* |
Cytokeratin |
Negative |
NEGATIVE |
NEGATIVE |
The "*" indicates important immunohistochemical stains used to distinguish this entity from the other malignancies entertained in the differential diagnosis. Due to the morphology and negative cytokeratin, an immunohistochemical stain for prostate specific antigen was not performed.
FINAL DIAGNOSIS:
LYMPH NODE, LEFT NECK, FINE NEEDLE ASPIRATION
SATISFACTORY FOR INTERPRETATION
POSITIVE FOR MALIGNANT CELLS
MALIGNANT NON-HODGKINS LYMPHOMA (ALK-1 POSITIVE ANAPLASTIC LARGE CELL LYMPHOMA)
DISCUSSION:
As stated above, this case was signed out as a malignant neoplasm, immunohistochemical stains support the diagnosis of ALK positive anaplastic large cell lymphoma. ALCL is a T- cell lymphoma consisting of lymphocytes that are usually large with abundant cytoplasm and pleomorphic often horse-shaped nuclei, which were appreciated in the cellblock. This case is of interest because of the fact that the diagnosis was made on fine needle aspiration.
Fine needle aspiration (FNA) is considered a major diagnostic tool in the initial investigation of lymphadenopathy. There has been some debate as to the use of fine needle aspiration in the initial diagnosis of Hodgkin and non-Hodgkin lymphoma. However, there is agreement as to the use of FNA in determining residual disease and/or relapse. In this particular case, enough material was available in the cell block to definitively establish the diagnosis by immunohistochemistry, despite the presence of so few of the characteristic morphologic features of anaplastic large cell lymphoma.
Since the late 1980's it was recognized that a t (2;5) (p23;q35) translocation in CD30 positive large cell lymphomas (anaplastic large cell lymphomas [ALCL]). It is now know that approximately 60-85% of ALK positive cases have a translocation resulting in the fusion of ALK (anaplastic lymphoma kinase) protein, a transmembrane protein on chromosome 2, with NPM (nucleophosmin), a nuclear transport protein on chromosome 5. ALK is absent from post natal tissue and can be positive in rare cases of diffuse large B-cell lymphoma expressing cytoplasmic IgA and showing an immunoblastic /plasmablastic morphology. It is also rarely expressed in rhabdomyosarcomas and inflammatory myofibroblastic tumors.
ALCL accounts for 3% of all adult Non Hodgkin Lymphoma and 10-30% of childhood lymphomas. ALK-1 positive ALCL are more frequent in the first 3 decades of life while ALK-1 negative ALCL are more prevalent in older individuals. Despite the patient's older age, it was found to be an ALK positive ALCL. The AKL negative cases seem to be associated with a more aggressive clinical course. ALK positivity has been associated with a favorable prognosis. In patients who are ALK positive, the overall five-year survival is 80%, in contrast to only 40% for ALK negative patients.
This case represents the common variant of anaplastic large cell lymphoma. The typical immunophenotype, which can be reviewed in Table 1, consists of positive staining of CD30, ALK, and EMA, as well as a large population showing positive staining for CD2 and CD4. Most cases of ALCL express cytotoxic granules. CD3 is negative in greater than 75% of cases. A T-cell or null cell phenotype can be present. ALCL is consistently EBV negative (EBER in-situ and LMP-1).
ALCL can be divided into three distinct morphologic subtypes:
ALCL, common variant (70%) consist of pleomorphic large cells with hallmark features (eccentric, horseshoe or kidney -shaped nuclei)
ALCL, lymphohistiocytic variant (10%) consists of larger and more pleomorphic cells with more prominent nuclei; these tumor cells are admixed with histiocytes and the neoplastic cells cluster around blood vessels
ALCL, small cell variant (5-10%) consists of small to medium neoplastic cells with irregular nuclei (often misdiagnosed as peripheral T- cell lymphoma unspecified)
REFERENCES:
Contributed by Maurice R. Grant, MD and Fiona Craig, MD
  |
