Cutaneous Vasculopathy and Recalcitrant Lower-Extremity Ulcerations

T-cell prolymphocytic leukemia (T-PLL) is an aggressive malignancy with a poor prognosis. Precise pathologic assessment of the phenotype of intravascularly observed cells is necessary, as several other conditions, including lymphomatoid granulomatosis, intravascular large B-cell lymphoma, and other leukemias and lymphomas with an intravascular component, may present identically (1). T-PLL presents with skin involvement in approximately 25% of patients, with cutaneous lesions most often consisting of maculopapular rashes or nodules (2). Recalcitrant lower-leg ulcers, as in the case of our patient, are an unusual manifestation of T-PLL.

To describe an unusual case of T-PLL that initially presented as persistent, worsening leg ulcerations and to highlight the importance of multiple skin biopsies in cases with several morphologic cutaneous changes.

A 30-year-old woman was admitted for large, painful, progressive, bilateral lower-extremity ulcerations. She reported a 15-year history of recurrent ankle swelling as well as intermittent painful and tender nodules on her legs and feet. Multiple skin biopsies performed at her initial presentation demonstrated subcutaneous inflammation most suggestive of erythema nodosum, and initial imaging demonstrated no lymphadenopathy or hepatosplenomegaly. She was treated with repeated courses of oral prednisone, typically 3 to 4 times a year. She noted an increase in the severity of her symptoms during 2 pregnancies, which were successfully carried to term, but otherwise did not note any other modifying factors. One and a half years before admission, she noted an escalation of her symptoms. In addition to the same ankle swelling and tender nodules on her legs and feet, she noted progression of these nodules to painful leg ulcers. She also developed intermittent oral and vaginal ulcerations. Doppler ultrasound of the lower extremities suggested venous stasis, and a skin biopsy showed evidence of a thrombotic vasculopathy. She had an extensive hematology and rheumatology work-up, which was unremarkable except for an elevated C-reactive protein, erythrocyte sedimentation rate, and a mildly elevated C3. She also had leukocytosis and hyperglycemia, both of which were attributed to chronic systemic steroid treatment. Treatment before admission included wound care and leg compression, systemic corticosteroid therapy, methotrexate, hydroxychloroquine, aspirin, and rivaroxaban. Progression of her condition prompted referral to our institution and subsequent admission.

On physical examination, the patient had large, extremely tender, irregularly shaped circumferential leg ulcers, with violaceous and purpuric borders, areas of eschar, and a fibrinous base (Figure 1, A). She had reticulated erythema and purpura on her hands (Figure 1, B) and faintly erythematous, blanching macules and papules coalescing into patches and thin plaques on bilateral thighs (Figure 1, C). She also had genital and oral ulcers. Given the atypical, progressive, and recalcitrant nature of her leg ulcerations, multiple skin punch biopsies were performed to sample the different morphologic changes on her skin. A biopsy from a thin plaque on her left thigh revealed a monomorphic, perivascular, and periadnexal atypical lymphocytic infiltrate (Figure 2, A). Skin biopsy on the purpuric edge of the leg ulceration revealed epidermal necrosis with numerous fibrin thrombi and an intra-/perivascular atypical lymphocytic infiltrate that showed monotony and hyperchromasia (Figure 2, B and C). On immunohistochemical staining, the lymphocytes were CD3-positive T cells coexpressing CD4 and CD8 with preserved expression of CD7 (Figure 2, C). The histopathologic findings were those of an atypical lymphocytic infiltrate with findings concerning for secondary cutaneous involvement by a systemic leukemia/lymphoma. These results prompted peripheral blood flow cytometry studies, which showed a phenotypically abnormal T-cell population that demonstrated expression of CD52. The overall findings were diagnostic of T-PLL. Systemic work-up revealed splenomegaly and involvement of her retroperitoneal, pelvic, and inguinal lymph nodes. The patient was treated with a 12-week course of alemtuzumab and then received a matched unrelated donor stem cell transplant. Posttransplant course was complicated by acute graft-versus-host disease affecting the gastrointestinal tract and Corynebacterium striatum bacteremia that resolved with vancomycin. The ulcerations on her lower extremities have since healed 127 days posttransplant, with only atrophic and nodular scarring remaining (Figure 1, D).

Lower-extremity ulcerations have an estimated prevalence of 1% to 2% in the United States and are a common cause of inpatient hospitalization (3, 4). For the minority of nonhealing leg ulcers not otherwise explained by chronic arterial or venous disease, the differential diagnosis includes infection, panniculitis, calciphylaxis, vasculitis or other immune-mediated etiologies, and malignancy (5).

The young age of our patient, the severe and progressive nature of her ulcerations, and the associated mucocutaneous findings are suggestive of an alternative underlying disease process. In addition, the presence of retiform erythema, as seen in this case, is a critical observation that should prompt further investigation of underlying causes of vasculopathy and/or medium- to large-vessel vasculitis. Skin biopsy is crucial in the diagnosis of both cutaneous ulcers and retiform purpura of unclear cause, and repeat biopsies should be strongly considered for patients with ulcers recalcitrant to treatment or with acute on chronic worsening. Capturing an intravascular pathology on skin punch biopsies can be challenging, and careful selection of the appropriate biopsy site is needed.

It is unclear whether the patient's early skin findings were already part of an evolving T-PLL. T-PLL is a rare condition, and its natural history and evolution is still poorly understood. Although her primary presenting cutaneous problem was her recalcitrant leg ulcers, her physical examination findings clearly indicated a more widespread, vasculopathic process. Our case not only represents a unique presentation of T-PLL responsive to bone marrow transplant but also illustrates the importance of maintaining a broad differential when faced with recalcitrant lower-extremity ulcerations.