—  SPECIALTY CONFERENCE  —

Hematopathology

Case 1 - Classic HCL Manifesting in Peripheral Lymph Node with Concurrent Massive Bone Marrow Effacement

Kathryn Foucar
University of New Mexico
Albuquerque, NM


Click on each slide thumbnail image for an enlarged view
Clinical:
This 53-year-old female with a 2-year history of neutropenia presents with an enlarged right axillary lymph node. Following lymph node biopsy, a bone marrow aspirate and biopsy were performed. The bone marrow was inaspirable.

CBC:   Differential count:
WBC 4,100/µL Neutrophils 34%
RBC 4.2 x 106/µL Lymphocytes 60%
Hgb 13.1 g/dL Monocytes 2%
Hct 38% Eosinophils 3%
MCV 91 fl Basophils 1%
Plt 156,000/µL



Case 1 - Figure 1 - Low power photomicrograph of right axillary lymph node (H&E)
Case 1 - Figure 2 - Intermediate power - right axillary lymph node (H&E)
Case 1 - Figure 3 - High power medullary region of right axillary lymph node (H&E)


Case 1 - Figure 4 - Peripheral blood smear (Wright's)
Case 1 - Figure 5 - Low power photomicrograph of bone marrow core biopsy (H&E)
Case 1 - Figure 6 - Intermediate power photomicrograph of bone marrow core biopsy (H&E)


Case 1 - Figure 7 - High power photomicrograph of bone marrow core biopsy (H&E)
Case 1 - Figure 8 - Bone marrow core biopsy (reticulin)


Differential Diagnosis:

A. Classic Hairy Cell Leukemia

Hairy cell leukemia (HCL) classically affects middle aged to elderly patients, often men, who present with splenomegaly and pancytopenia. Hairy cell leukemia can occur as early as the third decade of life, but it is extremely unusual in patients less than 30 years of age. Although splenomegaly is a hallmark of HCL, because of earlier detection the incidence of marked splenomegaly in HCL patients has declined. Hepatomegaly is variable but common, while most patients with HCL lack significant lymphadenopathy. However, localized lymphadenopathy was present in the current case.

Hematologic features of HCL
Either single or multilineage cytopenias dominate blood findings in patients with HCL. Leukopenia, characterized by both neutropenia and marked monocytopenia, is the most common abnormality. Anemia is also a frequent finding in patients with HCL. The search for classic hairy cells in the blood is often a time-consuming endeavor, because of their low numbers. Both nuclear and cytoplasmic features contribute to the "classic" HCL morphology. The nuclei of hairy cells tend to be round or reniform and exhibit a dispersed "spongy" chromatin configuration. Cytoplasm is moderate to abundant in amount, pale, and demonstrates circumferential hairy projections.

Bone Marrow Findings in HCL
Although the bone marrow is frequently inaspirable due to reticulin fibrosis, the bone marrow biopsy is invaluable in establishing a diagnosis of HCL. Unlike virtually all other B-CLPDs, discrete nodular infiltrates of leukemia are extremely rare in HCL. Instead, bone marrow biopsy sections reveal either subtle patchy infiltrates of hairy cells, or a diffuse interstitial pattern of infiltration. Sinusoidal infiltration by HCL is common and may be highlighted by CD20 and CD 34 staining. In some cases the infiltrates of HCL are so inconspicuous that they may be missed on initial evaluation. Staining of these bone marrow biopsy sections with a pan-B cell antigen such as CD20 or with DBA.44 greatly enhances the identification of these subtle hairy cell infiltrates. The concurrent expression of DBA.44 and TRAP by immunohistochemical staining demonstrates high specificity for HCL. The diffuse interstitial infiltrates of hairy cell leukemia are characterized by widely spaced oval to reniform nuclei. A "fried-egg" appearance may be evident.

Lymphadenopathy is unusual in HCL and generally consists of radiographically-detected abdominal adenopathy in HCL patients with fairly longstanding disease (25% of cases in one reference). Peripheral lymphadenopathy, as seen in our patient, is very uncommon. The disease course of HCL is generally indolent with excellent response to therapy, notably 2-CDA.

B. Marginal Zone Lymphoma (MZL)

Node-based, extranodal, and splenic marginal zone lymphomas have all been described and characterized by morphologic, immunophenotypic, and genetic parameters. Overlap with HCL is most commonly encountered in blood and bone marrow specimens. The distinctive medullary involvement in the current patient's lymph node specimen is unusual for nodal MZL.

Splenic marginal zone lymphoma with villous lymphocytes typically affects elderly men who present with symptoms secondary to splenomegaly. Peripheral blood examination reveals mild anemia and/or thrombocytopenia, while the white blood cell count is moderately elevated, rarely exceeding 40,000/mm3.

Nodal MZL (NMZL), extranodal MZL (EMZL), and splenic MZL (SMZL) can involve the bone marrow, although bone marrow involvement is clearly highest in SMZL with a frequency approaching 100%. About 50% of cases of NMZL and EMZL exhibit bone marrow infiltration which may be very subtle. Massive diffuse bone marrow effacement, as seen in the current case, is unusual for all types of MZL and is usually linked to prolonged disease in those rare cases of SMZL in which extensive bone marrow disease is described.

The disease course is generally indolent, and reports of spontaneous regression following effective therapy for hepatitis C have been published. Recent studies suggest that, analogous to CLL, mutation status of IgVH genes may predict disease course.

Differential Diagnosis Based on Immunophenotype:

Classic Immunophenotypic Profile of Selected B-Chronic Lymphoproliferative Disorders
  SMZL HCL† HCLv
SIg + + +
CD19 + + +
CD20 + + +
CD22 + + +
CD23* - , w - , w -
CD25 - + -
CD5 v - - -
FMC7 + + NA
CD11c v + +
CD10 v v -
CD79b + + +
CD103 - + +
Cyclin D1 - +s NA
v = variable expression; w = weakly expressed; c = cytoplasmic; +s = subset of cases positive
*weakly to moderately expressed on many leukemia substypes
†Additional immunophenotypic features of classic HCL include Annexin 1, DBA.44, and TRAP immunohistochemistry positivity. TIA-1 expression is also described in HCL (very unusual in other B-CLPD)


Diagnosis:
Classic HCL Manifesting in Peripheral Lymph Node with Concurrent Massive Bone Marrow Effacement.

HCL Cell of Origin:
Memory B cell (altered expression of chemokine and adhesion receptors)

HCL Unique Aspects:
HCL variant

Large cell transformation

Lymph node manifestations

References

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