A 35-year-old woman from Mumbai presents with a 4-week history of painless left axillary lymphadenopathy and pruritus. She denies fever or night sweats. Examination reveals a single firm, mobile, rubbery lymph node (3 cm) in the left axilla. CT chest/abdomen shows no other lymphadenopathy or organomegaly. Lymph node excision biopsy shows nodules of lymphoid tissue separated by broad bands of collagen fibrosis. Within the nodules are scattered large cells with clear cytoplasm and prominent nucleoli, admixed with small T lymphocytes. Immunohistochemistry shows these large cells are CD30^+^, CD15^+^, CD45^−^, and CD20^−^. What is the most likely diagnosis?

Explanation

## Diagnosis: Nodular Sclerosis Hodgkin Lymphoma ### Histologic Subtypes of Classical Hodgkin Lymphoma **Key Point:** The WHO classifies classical Hodgkin lymphoma into four subtypes based on the relative proportion of Reed-Sternberg (RS) cells and background inflammatory cells, and the pattern of fibrosis. | Subtype | RS Cell Frequency | Background | Fibrosis Pattern | Prognosis | Frequency | |---------|-------------------|-----------|-----------------|-----------|----------| | **Nodular Sclerosis** | Sparse | Mixed T cells, eosinophils | Broad collagen bands | Favorable | ~70% | | Lymphocyte-rich | Sparse | Abundant small lymphocytes | Minimal | Favorable | ~5% | | Mixed cellularity | Numerous | Mixed inflammatory cells | Diffuse, no broad bands | Intermediate | ~15% | | Lymphocyte-depleted | Numerous | Sparse lymphocytes | Diffuse | Poor | ~5% | ### Why Nodular Sclerosis? **High-Yield:** The **broad bands of collagen fibrosis** separating nodules of lymphoid tissue is the defining histologic feature of nodular sclerosis Hodgkin lymphoma. This fibrosis pattern is absent or minimal in other subtypes. **Clinical Pearl:** Nodular sclerosis is the most common subtype and typically presents with: - Mediastinal or supraclavicular involvement (though axillary as in this case is possible) - Young to middle-aged adults - Favorable prognosis with modern chemotherapy - Absence of B symptoms in ~40% of cases (as seen here) ### Immunophenotype Confirmation The CD30^+^, CD15^+^, CD45^−^, CD20^−^ profile confirms Hodgkin cells (and RS cells): - **CD30^+^** — activation marker; present on RS/Hodgkin cells - **CD15^+^** — myeloid antigen; present in ~75% of classical HL - **CD45^−^** (CD20^−^) — absent common leukocyte antigen; excludes reactive B cells and non-Hodgkin lymphomas **Mnemonic:** **HRSB** = **H**odgkin cells are **R**are, **S**parse, **B**ackground-rich (in nodular sclerosis) ### Why Not Lymphocyte-Rich? **Key Point:** Lymphocyte-rich classical HL has abundant small lymphocytes with minimal fibrosis and no broad collagen bands. The prominent fibrosis here excludes this subtype. [cite:Robbins 10e Ch 13]