#dermpathJC December 2021 summary

Thursday, December 9th, 9pm EST

Article discussed: Secondary skin involvement in classic Hodgkin lymphoma: Results of an international collaborative cutaneous lymphoma working group study of 25 patients.

Authors: Gru, A., Bacchi, C. E., Pulitzer, M., Bhagat, G., Kempf, W., Robson, A., Plaza, J. A., Pincus, L., Raghavan, S., Xu, M., Vencato da Silva, T., Salavaggione, A. L., Subtil, A., & Battistella, M.

Temporary free access courtesy of The Journal of Cutaneous Pathology: https://onlinelibrary.wiley.com/doi/abs/10.1111/cup.14077

Summary prepared by: Suzy Bloomquist, MD (@BloomquistSuzy)

Journal Club Summary:

Overview:

While Hodgkin lymphoma (HL) is a fairly common B cell lymphoma overall in the US (approx. 9000 new cases per year); it is exceedingly RARE in the skin and when present is ALWAYS considered to be a secondary involvement of systemic HL. Simply put, the concept of primary cutaneous HL no longer exists.
Many previously reported examples of so-called primary cutaneous HL are now considered to be most likely cases of misdiagnosed lymphomatoid papulomatosis and cutaneous anaplastic large-cell lymphoma which both have overlapping histomorphology and immunophenotypic features with classic HL.
Possible mechanisms of skin involvement: “hematogenous dissemination, direct extension from involved lymph nodes, and retrograde lymphatic spread from proximally involved lymph nodes”
Implications of skin involvement: usually means the patient has stage IV disease (unless locoregional spread from nearby lymph node)

Tips:

Clinical presentation:
- In this series:
  - 84% with cutaneous involvement by HL had stage IV disease
  - 67% showed skin lesions involving HL relapse
  - 28% of skin lesions present at time of diagnosis
  - 56% presented with solitary skin nodule (ulcerated lesion in 25%)
cd30
Histopathology:
- Mixture of inflammatory cells, spares epidermis
- Large RS cells may be difficult to find
- +/- fibrotic bands (nodular sclerosis subtype)
- Commonly present in the subcutaneous tissue, one case of “panniculitic” involvement
Useful IHC:
- Classic HL: CD30+, CD15+ (usually although some exceptions), PAX-5 weak/dim
  - Negative: CD20 (or weak/focal in few), CD45
  - +/- MUM-1 (non-specific)
  - EBER may be positive
  - CD3+ T cells in background

Differential diagnosis with accompanying immunohistochemistry:

In more detail below:
- - Lymphomatoid papulomatosis (LyP):
    - Lacks classic RS cells, PAX-5 (-)
  - Cutaneous anaplastic large cell lymphoma (C-ALCL):
    - Shows dense diffuse infiltrate of the large atypical cells, cells have hallmark appearance, PAX-5 (-)
  - EBV+ mucocutaneous ulcer:
    - Clinical presentation different: around mouth or other mucosal surfaces, patients immunosuppressed and with shallow ulcers
    - NEED history as IHC pattern is very similar
  - EBV+ diffuse large B-cell lymphoma:
    - Cell types: mixture of centroblasts, immunoblasts, pleomorphic cells, RS-like cells, variable lymphocytes and histiocytes
    - Solid sheets of EBV+ cells
    - Strong PAX-5
  - Large B-cell lymphoma, unclassifiable with intermediate features between CHL and diffuse large B-cell lymphoma (gray zone lymphoma):
    - Strong expression of at least one B cell marker (CD20, CD79a, CD15)
  - Post-transplant lymphoproliferative disorders (PTLD):
    - Rarely CHL-like morphology, especially after solid organ transplant
    - Clinical history key

Helpful images:

Figure 1 from paper: Classic HL, nodular sclerosis type – dense dermal lymphocytic infiltrate sparing the epidermis, vague nodular pattern, classic RS cells seen with background mixed inflammatory infiltrate.

Figure 4 from paper: Classic HL, nodular sclerosis type (note nodularity plus bands of fibrosis) IHC staining pattern: note numerous CD3+ T cells in background (neoplastic cells negative). CD30+ (strong, diffuse), PAX-5 is dim in neoplastic cells contrasted to strong staining in background reactive B cells.

Figure 5 from paper: Classic HL, mixed cellularity type. Mixture of cells, no fibrosis, epidermis spared. Note mummified cells. Only rare conventional RS cells.

By popular demand, Dr Cha (@sunpungi) and Dr Gottesman (@SGottesmanMD) prepared a follow up YouTube video Q&A session with Dr Alejandro Gru (@alegru18), available at the embedded video link below: