HIV Insight: Human Immunodeficiency Virus-Positive Secondary Syphilis Mimicking Cutaneous T-Cell Lymphoma

Malignant syphilis or lues maligna is a severe form of secondary syphilis that was commonly reported in the pre-antibiotic era, and has now reemerged with the advent of the human immunodeficiency virus (HIV) epidemic. However, the characteristic histopathological findings of malignant syphilis remain controversial.

The aim of this case report was to clarify the clinical and histopathological findings of HIV-positive malignant secondary syphilis. A Japanese man in his forties complained of fever, skin lesions, headache, and myalgia without lymphadenopathy during the previous 4 weeks. The skin lesions manifested as erythematous, nonhealing, ulcerated papules scattered on his trunk, extremities, palm, and face.

Although the skin lesions were suspected to be cutaneous T-cell lymphomas on histological analyses, they lacked T-cell receptor Jγ rearrangement; moreover, immunohistochemical analyses confirmed the presence of spirochetes. The patient was administered antibiotics and anti-retroviral therapy, which dramatically improved the symptoms. On the basis of these observations of the skin lesions, we finally diagnosed the patient with HIV-associated secondary syphilis that mimicked cutaneous T-cell lymphoma.

The patient’s systemic CD4+ lymphocyte count was very low, and the infiltrate was almost exclusively composed of CD8+ atypical lymphocytes; therefore, the condition was easily misdiagnosed as cutaneous lymphoma. Although the abundance of plasma cells is a good indicator of malignant syphilis on skin histological analyses, in some cases, the plasma cell count may be very low.

Therefore, a diagnosis of malignant secondary syphilis should be considered before making a diagnosis of primary cutaneous peripheral T-cell lymphoma or lymphoma associated with HIV infection.

Below: Clinicopathological findings. a. Skin lesions before treatment. These 1–5-cm erythematous lesions were scattered on the trunk. Lesions larger than the size of a walnut were ulcerated and crusty. Palmer and planter lesions were also present. b. Nodular infiltration of the cells from the epidermis to the upper subcutaneous. c. Epidermotropism of atypical lymphoid cells. d. In the dermis, there is severe inflammation around the venules. Atypical lymphocytes, multinucleated leukocytes, and epithelioid histiocytes are present, but sparse plasma cells. e. Immunohistochemical staining for CD8. Lymphocytes were exclusively immunoreactive for CD8. Atypical lymphocytes with nuclear twisting and indentation are also present (arrows). f. In the bone marrow clot, a number of CD8+ lymphocytes are infiltrating, as indicated by immunohistochemistry. g. Atypical lymphocytes and small lymphocytes are seen in the bone marrow smear, suggestive of non-neoplastic cells (arrowheads). h. Treponema pallidum is mainly distributed in the dermis, especially in the perivascular space with histiocytes. Immunohistochemical staining for Treponema pallidum