Less Common Lymphoid and Myeloid Malignancies¶
Chapter 115 | Part 4: Oncology and Hematology
KEY CLINICAL POINTS¶
- NLPHL is distinct from classical Hodgkin lymphoma (cHL) and shares features with indolent B-cell NHLs.
- Hairy cell leukemia (HCL) is a rare B-cell malignancy with splenomegaly and BM involvement.
- Chronic neutrophilic leukemia (CNL) is characterized by clonal neutrophil proliferation and CSF3R mutations.
- Hyper eosinophilic syndrome (HES) involves clonal eosinophilia with organ damage and KIT mutations.
- Mastocytosis is defined by mast cell accumulation with CD117/CD25 expression and KIT D816V mutations.
1. DEFINITION & OVERVIEW¶
Less common lymphoid and myeloid malignancies encompass rare entities distinct from common leukemias and lymphomas. These include NLPHL, HCL, splenic marginal zone lymphoma, and various myeloid neoplasms. Diagnosis requires exclusion of reactive processes and differentiation from other malignancies.
Table 115-1: Unusual Lymphoid and Myeloid Malignancies¶
| Lymphoid | Myeloid |
|---|---|
| B-cell prolymphocytic leukemia | Chronic neutrophilic leukemia |
| Splenic marginal zone lymphoma | Chronic eosinophilic leukemia |
| Hairy cell leukemia | Histiocytic sarcoma |
| Nodal marginal zone B-cell lymphoma | Langerhans cell histiocytosis |
| Mediastinal large B-cell lymphoma | Mast cell sarcoma |
1.1 Nodular Lymphocyte-Predominant Hodgkin Lymphoma (NLPHL)¶
NLPHL is an indolent B-cell neoplasm with L&H cells (CD20+, CD15 − , CD30 − ) and a clinical course similar to indolent NHL. Treatment depends on stage and symptoms.
1.2 Hairy Cell Leukemia¶
HCL is a rare B-cell malignancy with splenomegaly, BM involvement, and CD20+ cells. Treatment includes purine analogs (cladribine) and rituximab.
2. EPIDEMIOLOGY¶
NLPHL affects males more frequently (75% of cases) with bimodal age distribution (children and adults 30–40 years). HCL is more common in males and associated with alkylating agent exposure. CNL incidence is ~0.1 cases/million/year.
2.1 Risk Factors¶
Age, gender, prior chemotherapy (alkylating agents), and immune deficiencies (e.g., HIV, autoimmune diseases) are key risk factors.
3. ETIOLOGY & PATHOPHYSIOLOGY¶
Genetic mutations (e.g., CSF3R, SF3B1, KIT D816V) and immune dysregulation drive these malignancies. NLPHL involves B-cell clonal expansion with L&H cells. HCL is associated with BRAF V600E mutations.
3.1 Molecular Mechanisms¶
CNL: CSF3R mutations; HES: KIT D816V; HCL: BRAF V600E; Mastocytosis: KIT D816V.
4. CLINICAL FEATURES¶
Symptoms vary by disease: splenomegaly, lymphadenopathy, constitutional symptoms, and organ-specific manifestations (e.g., hepatosplenomegaly, skin lesions).
Table 115-2: Immunophenotype of Small Lymphocyte Tumors¶
| CD5 | CD20 | CD43 | CD10 | CD103 | sIG | CYCLIN D1 |
|---|---|---|---|---|---|---|
| neg | pos | pos | pos | neg | pos | neg |
| pos | pos | pos | neg | neg | pos | pos |
| neg | pos | neg | neg | neg | pos | neg |
| neg | pos | ? | neg | pos | pos | neg |
4.1 NLPHL¶
Indolent course with splenomegaly, lymphadenopathy, and B-symptoms (fever, night sweats).
4.2 HES¶
Eosinophilia with organ damage (cardiac, GI, skin) and systemic symptoms (fever, weight loss).
5. DIFFERENTIAL DIAGNOSIS¶
Differentiate from reactive processes (e.g., infections, inflammation), other lymphomas, and myeloproliferative neoplasms. Key features include clonal markers and organ-specific involvement.
Table 115-3: Differential Diagnosis of 'Dry Tap'¶
| Cause | Frequency |
|---|---|
| Metastatic carcinoma | 17% |
| Chronic myeloid leukemia | 15% |
| Cause | Frequency |
|---|---|
| Myelofibrosis | 14% |
| Hairy cell leukemia | 10% |
| Acute leukemia | 10% |
| Lymphomas, Hodgkin's disease | 9% |
5.1 HES vs. Reactive Eosinophilia¶
Clonal markers (KIT D816V), organ damage, and persistent eosinophilia (>1.5×10 I /L) distinguish HES from reactive causes.
6. INVESTIGATIONS & DIAGNOSIS¶
Diagnostic workup includes flow cytometry, cytogenetics, molecular testing (e.g., KIT, CSF3R), and imaging. Bone marrow biopsy is critical for myeloid neoplasms.
Table 115-4: ICC Classification of Myeloid Neoplasms¶
| Category | Subtypes |
|---|---|
| Acute myeloid leukemia (AML) | AML with KMT2A rearrangement |
| Myelodysplastic syndromes (MDS) | MDS with mutated TP53 |
| Myeloproliferative neoplasms (MPN) | Chronic neutrophilic leukemia |
| MDS/MPN overlap | Chronic myelomonocytic leukemia (CMML) |
6.1 Molecular Testing¶
CSF3R mutations for CNL, KIT D816V for mastocytosis, and SF3B1 mutations for MDS/MPN.
7. MANAGEMENT & TREATMENT¶
Treatment varies by disease: chemotherapy (CHOP, R-CHOP), targeted therapy (BRAF/MEK inhibitors), and stem cell transplantation. Supportive care includes corticosteroids and cytoreduction.
Table 115-5: ICC Diagnostic Criteria for CNL, aCML, CMML¶
| Variable | CNLa | aCML | CMML |
|---|---|---|---|
| PB leukocyte count | ‡13×10n/L | ‡13×10n/L | ‡13×10n/L |
| PB neutrophil precursors | <10% | ‡10% | ‡10% |
| PB monocyte count | <10% of leukocytes | No or minimal monocytosis | ‡0.5×10n/L |
7.1 HES¶
First-line: corticosteroids (prednisone). Second-line: mepolizumab, rituximab, or ASCT for advanced disease.
8. PROGNOSIS & COMPLICATIONS¶
Prognosis varies: NLPHL is curable, while HES and mastocytosis have variable outcomes. Complications include organ damage, secondary malignancies, and treatment-related toxicity.
8.1 CNL¶
Median survival ~2 years. Poor prognosis with leukemic transformation or treatment resistance.
9. SPECIAL CONSIDERATIONS¶
Pregnancy: Avoid alkylating agents. Pediatric: Monitor for JMML. Elderly: Consider ASCT for high-risk disease. Immune suppression: Monitor for opportunistic infections.
9.1 Juvenile Myelomonocytic Leukemia (JMML)¶
Common in children, associated with RAS pathway mutations. Treatment: ASCT for high-risk cases.
10. KEY POINTS & CLINICAL PEARLS¶
- NLPHL is distinct from cHL and shares features with indolent NHL. 2. HCL is treated with purine analogs. 3. CNL requires CSF3R mutation confirmation. 4. HES is clonal with KIT D816V. 5. ASCT is curative for high-risk myeloid neoplasms.