Why Clinical Context is Key for Rare Cases and Diverse Skin Types

Clay J. Cockerell, MD, owner of Cockerell Dermatopathology in Dallas, Texas, and Andrew F. Alexis, MD, MPH, professor of clinical dermatology and Vice-Chair for Diversity and Inclusion at Weill Cornell Medicine in New York City, delivered complementary Winter Clinical Miami lectures in diagnostic vigilance and therapeutic nuance, underscoring how pattern recognition, clinicopathologic correlation, and tailored treatment strategies directly impact patient outcomes.

The Toughest Clinical Cases

Cockerell opened with a reminder that dermatology is fundamentally about solving complex visual puzzles—and that accurate diagnosis depends on meaningful clinical information.¹ He stressed that vague requisitions such as “rash, unspecified” undermine dermatopathologic accuracy, particularly in challenging cases where history and photographs are critical.

One striking example involved a patient with a remote history of melanoma who later developed a lesion clinically presumed benign. Histologically, the biopsy resembled granuloma annulare, with interstitial histiocytic inflammation. However, immunohistochemistry revealed strong SOX10 positivity, confirming metastatic melanoma mimicking a granulomatous process. The case illustrated how metastases can masquerade as inflammatory dermatoses and reinforced the importance of clinicopathologic correlation.

Another case featured a pediatric patient with enlarging plaques ultimately diagnosed as Wells syndrome (also known as eosinophilic cellulitis). The presence of “flame figures”—eosinophil granule proteins coating collagen—highlighted a classic but uncommon histologic clue. Cockerell emphasized that flame figures are not pathognomonic and may appear in other eosinophilic disorders, reinforcing the need for clinical context.

Global dermatology also played a role in the discussion. A patient with longstanding nodular lesions acquired in Guyana was diagnosed with lobomycosis (also known as keloidal blastomycosis), caused by Lacazia loboi. The organism cannot be cultured and produces keloid-like nodules filled with yeast-like structures. Interestingly, the disease also affects bottlenose dolphins in warm coastal waters. The case underscored the importance of travel and occupational history in evaluating unusual cutaneous infections.

Cockerell then turned to hematologic malignancies presenting with cutaneous findings. Intravascular large B-cell lymphoma was highlighted as a rare but serious cause of retiform purpura, characterized histologically by malignant lymphocytes confined within vessel lumina. He urged clinicians to biopsy unexplained purpuric eruptions rather than attributing them prematurely to vasculitis or coagulopathy.

Similarly, blastic plasmacytoid dendritic cell neoplasm (formerly hematodermic neoplasm) was presented as a “bruise-like” lesion that may initially appear deceptively benign. Immunostaining for CD123, CD4, and CD56 is diagnostic. Given the historically poor prognosis—but emerging targeted therapies—early recognition is critical. The overarching message: persistent, atypical bruises warrant biopsy.

Skin of Color Therapeutic Pearls

Alexis, a Dermatology Times Editorial Advisory Board member, shifted the focus to therapeutic optimization in patients with skin of color, emphasizing that pigmentary alteration often carries as much psychosocial burden as the primary inflammatory disease.²

In psoriasis and atopic dermatitis, skin of color patients frequently seek not only control of scaling and pruritus but also normalization of dyspigmentation. Targeted systemic therapies, including biologics and JAK inhibitors, have demonstrated progressive improvement in post-inflammatory hyperpigmentation (PIH) over months to a year. Importantly, patients should be counseled that pigmentary resolution lags behind inflammatory control.

He cautioned against misinterpreting active inflammation as residual hyperpigmentation. In darker skin tones, erythema may appear violaceous or gray rather than bright red, and subtle scale or induration may signal ongoing disease.

Seborrheic dermatitis presents unique considerations in patients of African descent, where hypopigmentation may predominate and hair care practices influence treatment adherence. Adjusting shampoo frequency recommendations and counseling on oily scalp products are essential. Newer vehicles, such as roflumilast foam, simplify management across diverse hair types.

For hyperpigmentation disorders, including acne-induced PIH and melasma, Alexis reviewed advances beyond hydroquinone. Fourth-generation retinoids, cysteamine, thiamidol, and topical agents like picolinyl glycine derivatives expand long-term non-hydroquinone options. For refractory melasma, short-term off-label oral tranexamic acid can significantly enhance outcomes in appropriately selected patients.

He also emphasized recognition of dermal macular hyperpigmentation disorders such as lichen planus pigmentosus, which may present with violaceous-gray hues. These inflammatory conditions often respond to low-dose oral isotretinoin combined with topical anti-inflammatory agents, reframing them as immune-mediated rather than purely pigmentary disorders.

Together, the 2 presentations reinforced a shared theme: excellence in dermatology demands careful observation, thoughtful diagnostic evaluation, and individualized therapy, particularly when clinical appearances challenge conventional expectations.

References

1. Cockerell C. Dermatology CPC – The Toughest Clinical Cases. Presented at: 2026 Winter Clinical Miami Dermatology Conference; February 27-March 1, 2026; Aventura, FL.

2. Alexis A. Skin of Color Therapeutic Pearls. Presented at: 2026 Winter Clinical Miami Dermatology Conference; February 27-March 1, 2026; Aventura, FL.