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Presentation

Two Complex Dermatologic Cases: Systemic Amyloidosis Alopecia and Cutaneous Myeloid Sarcoma

Description

The presentation covered two dermatologic cases illustrating how skin findings can reveal serious systemic disease. The first case was a frail woman in her 60s with progressive diffuse patchy alopecia initially thought to be common nonscarring hair loss, but scalp biopsies showed decreased follicular density, sparse inflammation, diminished sebaceous glands, and abundant dermal amyloid on Congo red stain with apple-green birefringence. Subsequent workup demonstrated amyloid deposition in the colon, an IgG lambda monoclonal gammopathy, elevated lambda light chains, and lambda-restricted plasma cells in bone marrow, confirming systemic light-chain amyloidosis with skin and GI involvement plus multiple myeloma; the most specific cutaneous clue discussed was periorbital/pinch purpura. The second case involved an 83-year-old woman with multiple skin lesions and a biopsy initially considered a keloid, but histology showed a dense atypical dermal and subcutaneous infiltrate of pleomorphic cells. Immunostains were initially confusing, with CD4 and CD56 positivity raising the possibility of blastic plasmacytoid dendritic cell neoplasm, but additional markers favored monocytic/myeloid differentiation, including lysozyme and CD68, and ERG/CD31 positivity. Next-generation sequencing revealed a newly acquired NPM1 mutation on a background of TET2 and ASXL1 mutations, indicating transformation of myelodysplastic syndrome to acute myeloid leukemia and confirming cutaneous myeloid sarcoma as a sentinel manifestation of leukemic progression.

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Conclusions

Diffuse alopecia can be an initial clue to systemic AL amyloidosis and should prompt consideration of an underlying systemic plasma cell disorder rather than only common hair-loss diagnoses.
On scalp biopsy, a pattern of decreased follicular density, sparse inflammation, diminished sebaceous glands, and prominent eccrine structures can suggest amyloid-associated alopecia before special stains are done.
Congo red staining with apple-green birefringence remains the key confirmatory test for cutaneous amyloid deposition, with additional studies used to define light-chain type and systemic involvement.
Systemic AL amyloidosis may present with multiple skin findings, but periorbital purpura is the most specific cutaneous manifestation discussed in the presentation.
When amyloidosis is confirmed, evaluation for monoclonal gammopathy, bone marrow involvement, and GI disease is necessary because skin findings may reflect widespread systemic disease.
In the presented amyloidosis case, the hair loss was ultimately linked to lambda light-chain systemic amyloidosis associated with multiple myeloma, supporting plasma cell–directed therapy.
Myeloid sarcoma can present in the skin and mimic other neoplasms, so broad histologic and immunophenotypic workup is essential when morphology is highly atypical.
CD4 and CD56 co-expression alone is not sufficient to diagnose blastic plasmacytoid dendritic cell neoplasm because these markers can also occur in myeloid neoplasms.
An extended plasmacytoid dendritic cell immunohistochemical panel and negative myeloid markers are required to distinguish BPDCN from cutaneous myeloid sarcoma in difficult cases.
A newly acquired NPM1 mutation in a skin lesion, when absent in prior marrow, supports clonal evolution and transformation from MDS to AML.
Cutaneous myeloid sarcoma may be a sentinel lesion that appears before overt marrow progression, making skin biopsy and reflex molecular testing clinically important.
The two cases together emphasize that unusual skin findings can reveal serious systemic hematologic disease and that timely pathology correlation can change diagnosis and management.

WHO 5th edition criteria for BPDCN: extended plasmacytoid dendritic cell panel including CD123 plus another pDC marker such as TCF4, TCL1, CD303, or CD304, along with negative myeloid markers like lysozyme and MPO.
OnkoSight Advanced Myeloid Panel (BioReference) used for next-generation sequencing revealing a newly acquired NPM1 mutation, with prior TET2 and ASXL1 mutations retained.