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HODGKIN

 

 

Clasification:

Hodgkin is originated in B cell from germinal center. Stage is more important than histology in Hodgkin. It is divided basically in 2 different entities with different clinic, morphology and immunophenotype:
1. Nodular Lymphocytic Predominance(NLP) . The cell classically found in NLP is theLP cell (popcorn cell with lobulated nuclei and small nucleoli).
2. Classic: Lymphocyte rich (LR), Nodular Sclerosis (NS), Mixed cellularity (MC) and Lymphocyte depletion(LD).
MC, once was considered a wastebaskdet category for all the cases combining variants, for example MC mixed with NS or NS mixed with LR etc. It is now a true category in WHO classification. The cell found in classic Hodgkin is the Reed Sternberg (RS).

Clinical presentation:

All ages with peak in young adults and after 55 y/o. NLP single node. NS and LR generally localized (Stage I and II). LD generally advanced. 50% of MC and some NS are disseminated (stage III and IV), and therefore B symptoms appear. NLP, LR and LD are rare with very low incidence. Most cases of Hodgkin are NS or MC. If HIV patient with disseminated disease think in LD

Architecture in HE:

-Nodular: NLP, LR, NS. They may have some diffuse areas.
-Possible necrosis: Possible in NS, MC and LD. Geographic necrosis or necrotizing granulomas common in NS.
-Fibrosis and sclerotic bands: NS birrefringent bands around nodules. Small birrefringent areas possible in MC. Extensive fibrosis seen in fibrotic variant of LD.
-Progressive transformed germinal centers: NLP
-Remmanents of germinal centers or intact germinal centers: possible in Classic variants. Absent or blurry border in NLP.
-Total obliteration of architecture or difficult differentiation with other anaplastic tumors (may look sarcomatoid): LD.
-Epithelioid granulomas: common in MC and NLP.
-Fibrinoid or fibrillary material: LD.

Diagnostic cells:

-Classic RS: required for the first time diagnosis of classic Hodgkin.
-Variants: LP (popcorn): NLP. Variants of Hodgkin cell: mononuclear, pleomorphic and mumified, common in MC. Lacunars common but not exclusive of NS. Very pleomorphic and bizarre cells possible in LD
-Number of Hodgkin cells: LP < NS < MC < LD. Note that they are extremely abundant in LD reticular pattern with more RS cells that background cells but scant in fibrotic LD. Very easy to find in MC and NS. Relatively scant in LR.
-Location of diagnostic cells: Neoplastic cells inside nodules, regresive or intact germinal centers (highlighted with CD21+ meshwork) are present in NLP and LR. Prominent parafollicular location of RS cells in all variants, but common in MC. Syncytial aggregates of lacunar cells in syncitial variant of NS.

Background cells:

All cases of Hodgkin have plasma cells and histiocytes. Some histio and plasma cells are identified in NLP around nodules. Eos and PMNs are common in classic Hodgkin, particullary around residual follicles in MC and NS (rare in LR). Background cells are less in number than RS cells in LD.

Immunohistochemistry:

The basic pattern of IHC is totally opposed for the LP cell vs RS cell

LP CELL: CD20+/79a+/45+/15-/30-/BOB1+/OCT2+/EMA+
RS CELL: CD20-/79a-/45-/15+/30+/BOB1-/OCT2-/EMA-

Other stains for LP cell: EBER-, LMP1-, CD43-, BCL6+, IgD+. Ring or rosettes of T cells around LP cells is CD4+/CD3+/CD57+ (not seen in any Classic Hodgkin).

Other stains to request in the initial pannel for classic Hodgkin: PAX5+ in RS cell. EBER+/LMP1+ in 60% MC and 40% NS.

Differential Diagnosis:

NLP vs TCRBCL: TCRBCL diffuse, no nodules

ALCL vs Classic Hodgkin: ALCL PAX5-/EMA+/most ALK+

DLBC Anaplastic vs Classic Hodgkin: difficult differential. Both CD30 and they may overlap

PTCL vs Classic Hodgkin: both CD15+/30+ but neoplastic cell in PTCL have T markers

MC vs early phase of NS: difficult dx. No fibrosis. More lacunar cells in N

Prognosis:

Good px in general except for advanced NLP, massive mediastinal NS and HIV patients with LD

Main References:
Wikipedia
eMedicine
WHO classification of tumors of hematopoietic and lymphoid tissues

Rossai and Ackerman Surgical Pathology textbook
Sternberg Diagnostic Surgical Pathology textbook