Cutaneous Squamous Cell Carcinoma in HIV-Positive Patients: A Diagnostic Challenge

For people living with HIV (PLHIV), the intersection of immunosuppression and malignancy often creates complex clinical puzzles. While Kaposi sarcoma (KS) is a well-known opportunistic tumor in this population, other cutaneous malignancies can present with striking similarities, leading to potential diagnostic pitfalls. A recent case highlights how cutaneous squamous cell carcinoma (cSCC) can mimic KS, complicating the path to a correct diagnosis, and treatment.

The Diagnostic Overlap: When cSCC Mimics Kaposi Sarcoma

Cutaneous squamous cell carcinoma is the second most frequent non-melanoma skin cancer globally. In patients with HIV, cSCC often presents atypically, which can lead clinicians to mistake it for other opportunistic infections or tumors. This clinical overlap is particularly dangerous because the management strategies for cSCC and KS differ significantly.

In one notable case, a 64-year-old woman with well-controlled HIV infection on antiretroviral therapy presented with a progressively enlarging, exophytic lesion on her scalp. Because of the patient’s HIV status and the appearance of the lesion, there was a strong clinical suspicion of Kaposi sarcoma. However, the initial punch biopsy proved inconclusive, illustrating a common hurdle in diagnosing these aggressive skin cancers.

Why Immunosuppression Matters

Immunosuppression increases the risk of developing cSCC that is both aggressive and multifocal. These factors often delay the initial diagnosis, as the tumors may not follow the typical growth patterns seen in immunocompetent patients. This makes repeated histopathology and multidisciplinary evaluation essential for an accurate diagnosis.

An Unexpected Response to Chemotherapy

When a lesion is deemed inoperable and clinical suspicion of KS is high, doctors may turn to empirical treatment. In the aforementioned case, the patient was treated with liposomal doxorubicin at a dose of 20 mg/m², which is the standard chemotherapy for Kaposi sarcoma.

The result was unexpected: after four cycles of treatment, the lesion showed marked clinical and radiologic regression. While liposomal doxorubicin has limited off-label activity against other cutaneous malignancies, its effectiveness in this case allowed the lesion to shrink enough for surgical intervention.

Subsequent surgical excision finally provided a definitive diagnosis: keratinizing squamous cell carcinoma. The surgery achieved tumor-free margins, and the patient remained recurrence-free at a six-month follow-up.

Improving Diagnostic Accuracy in PLHIV

To avoid diagnostic pitfalls in HIV-positive patients, clinicians must look beyond the initial presentation. The case underscores several critical lessons for healthcare providers:

• Avoid Reliance on Single Biopsies: Inconclusive initial biopsies should prompt repeated sampling or deeper biopsies to capture the true nature of the tumor.
• Utilize Advanced Imaging: While basic imaging may show no bony involvement, advanced modalities like MRI or PET/CT are better suited to assess soft tissue involvement and distant spread.
• Maintain a Broad Differential: Even when a patient’s clinical history strongly suggests an opportunistic tumor like KS, the possibility of cSCC should remain on the table.

Key Takeaways for Patients and Providers

Frequently Asked Questions

Can cutaneous squamous cell carcinoma be treated with chemotherapy?

While surgery is the primary treatment for cSCC, chemotherapy—such as liposomal doxorubicin—may be used off-label or in specific cases where the lesion is inoperable or mimics other tumors, as seen in recent clinical reports.

Why is cSCC more aggressive in people with HIV?

Immunosuppression impairs the body’s ability to surveil and destroy malignant cells, which can lead to more rapid tumor growth and a higher likelihood of multifocal lesions.

What is the difference between cSCC and Kaposi Sarcoma?

cSCC is a malignancy of the squamous cells in the epidermis, whereas Kaposi sarcoma is a vascular tumor caused by Human Herpesvirus 8 (HHV-8). Though they can look similar on the skin, they require different long-term management strategies.

Looking Forward

As antiretroviral therapy continues to improve the lifespan and quality of life for people living with HIV, the focus of care is shifting toward managing age-related and immunosuppression-related malignancies. This case serves as a reminder that vigilance and a willingness to question an initial diagnosis are vital in providing the best possible outcomes for PLHIV.