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Case 21 - Discussion

Hematopathology Case

 

MICROSCOPIC EXAM:

  The lymph node is  entirely effaced by diffuse proliferation of small to medium sized lymphocytes. The tumor cells are monotonous with slightly irregular nuclei and occasional nuclear grooves. The nuclei have moderately dispersed chromatin and inconspicuous nucleoli. Several hyalinized small vessels are embedded with lymphocytes.

FLOW CYTOMETRY INTERPRETATION

 

Lymph node: A kappa monotypic B-cell population is detected, expressing CD5, CD19, CD20, CD38 and FMC7, and are negative for CD10 and CD23.

                                            

     Total events       A gate bright CD45+         

     analyzed = 43766   events = 36759 (85% of   

                        total nucleated cells)    

        CD45+/CD14-          100%             

        CD19+/CD3-            81%

        CD3+/CD19-            10%

        CD19+/CD20+           80%

        CD19+/CD38+           80%

        CD19+/CD10+           <2%

        CD5+/CD19+            81%

        CD5+/CD19-            13%

        CD19+/CD23+            3%

        CD10+/FMC+            81%

        CD26+                  2%

        CD2+/CD7+              7%

        CD3+/CD5+              8%

        CD3+/CD4+              4%

        CD3+/CD8+              4%

        CD16+                 <2%

        CD3-/CD56+            <2%

     Gated on CD19+ cells

        CD19+/sIg Kappa+      100%

        CD19+/sIg Lambda+     <2%

 
IMMUNOHISTOCHEMICAL STAINS

CD20

CD79a

CD3 CD5
BCL1 BCL2
BCL6 CD23
 
Ki67  
Mantle Cell Lymphoma
 

The Key Features

  • Architecture: monomorphic lymphoid proliferation with a vaguely nodular, diffuse or mantle zone growth pattern;

  • Cytology: small to medium size, slightly irregular nuclear contours; No neoplastic transformed cells resembling centroblasts, immunoblasts, or paraimmunoblasts;

  • Hyalinized small vessels commonly present;

  • CD5+, BCL1+, CD43+, CD10-/+, CD23-, BCL6-;

  • t(11;14)(q13;q32), IgH/CCND1 fusion gene.

 

CLINICAL FEATURES

  • MCL comprises approximately 3-10% of NHL;
  • Age: middle to older age, median age 60 years; M:F=2:1;
  • Location: mostly lymph nodes, also spleen and bone marrow; most common extranodal sites, GI tract and Waldeyer's ring;

  • Most cases of multiple lymphomatous polyposis of GI tract represent MCL;

  • Clinical features: most patients present with stage III or IV with lymphadenopathy,  hepatosplenomegaly; >50% of cases with massive splenomegaly and marrow involvement; >25% cases with peripheral blood involvement that can mimic prolymphocytic leukemia;

  • No transformation into large cell lymphoma, but can increase nuclear size, pleomorphism, chromatin dispersal and mitotic activity.

MICROSCOPIC FINDINGS

  • Architecture: effacement of lymph node by a monomorphic lymphoid proliferation with a vaguely nodular, diffuse or mantle zone growth pattern, or rarely a true follicular growth pattern;

  • Cytology: small to medium size, slightly larger than the normal lymphocytes; slightly irregular nuclear contours, resembling centrocytes but often have slightly less irregular nuclear contours; occasional round nuclei, resembling B-CLL/SLL;  the nuclei have moderately dispersed chromatin with inconspicuous nucleoli;

  • No neoplastic transformed cells resembling centroblasts, immunoblasts, or paraimmunoblasts; no pseudofollicles;

  • Hyalinized small vessels commonly present;

  • Many cases have scattered single epithelioid histiocytes with a "starry sky" appearance; they typically have pale-pink cytoplasm with no phagocytosis.

SUBTYPES/VARIANTS

  • Blastoid variants: younger age, medium 40 years,

    • Classic type: cells resemble lymphoblasts with dispersed chromatin and a high mitotic rate (>10/10HPF, often >20-30/10HPF);

    • Pleomorphic type: heterogeneous cells with large cleaved to oval nuclei and pale cytoplasm

  • Small round lymphocytes: more clumped chromatin, either admixed or predominant, mimicking small cell lymphoma;

  • Prominent foci of cells with abundant pale cytoplasm resembling marginal zone cell lymphoma.

IMMUNOHISTOCHEMISTRY AND SPECIAL STAINS

  • Positive for B-cell markers: CD 19, CD 20, CD 22, CD79a;

  • Positive for sIgM and sIgD;

  • CD5+, BCL2+, FMC7+, CD43+;

  • BCL1 (Cyclin D1) positive in most cases, even in CD5- cases;

  • CD10-/+, BCL6-, CD23-/+;

  • SOX11+, even in BCL1 negative cases

CYTOGENETIC STUDIES

  • t(11;14)(q13;q32), IgH/CCND1 fusion gene, resulting in over-expression Cyclin D1.

TREATMENT AND PROGNOSIS

  • Not indolent, but moderately aggressive. Median survival, 3-5 years.

REFERENCES

  • Practical Diagnosis of Hematologic Disorders, Fourth Edition. By Carl R. Kjeldsberg, 2006.
  • Jaffe ES, Harris NL, Stein H, Vardiman JW, editors. Pathology and genetics of tumours of haematopoietic and lymphoid tissues. World Health Organization classification of tumours. Lyon (France): IARC Press; 2001.