A 38-year-old Chinese female was referred to the Department of Dermatology, the People's Hospital of Zhengzhou University with a 10-month history of progressive generalized skin lesions. The lesions originate in her right leg skin as a small raised papule and expanded quickly to her extremities, trunk, neck, and face. Physical examination revealed diffuse cutaneous plaques, ulcerated painful nodules and bulla formation over the entire body, ranging in diameter from 1 cm to 6 cm. The progressively ulcerated painful nodules with violaceous border and covered with a hemorrhagic crust, which resembled pyoderma gangrenosum (Fig. 1). She had no history of skin disease, any other medical problems and any family history of malignancies. The patient was directed to our clinic with a presumed diagnosis of Pyoderma gangrenosum.
The patient underwent the usual staging examinations with clinical exam. Radiography and computer tomographic (CT) assessment did not reveal infiltrates or enlarged nodes in the chest. Abdominal ultrasound examination showed normal liver and spleen, and no enlarged lymph nodes. A complete body positron emission tomography-computed tomography (PET/CT) was performed to evaluate the lymphoma status (Fig. 2). None of these assessments uncovered another involved site except skin. In particular, the nasal and nasopharyngeal regions were free of disease.
Laboratory tests revealed a mild hemophagocytic syndrome, white cell count of 1.98 × 109/L with a normal differential count, a hemoglobin level of 78 g/L, MCV-88 fl, and platelet count of 166 × 109/L. The serum LDH was 948 U/L and alkaline phosphatase 123 U/L at time of diagnosis. The bone marrow was free of disease. Mycological tests, including microscopic analysis of native specimens, and culture were negative. Hemoculture, human immunodeficiency serology, and hepatisis B and C viruses were negative. Biopsy from skin lesion was performed and histologic specimen slides stained with hematoxylin and eosin were reviewed by three pathologists. The pathological examination revealed a diffuse dermal lymphomatous infiltration of the skin. The lymphomatous infiltrate had an angiocentric and angiodestructive growth pattern with a mixed cell population accompanied by an admixture of inflammatory cells (Fig. 3a, b). Immunophenotyping was performed using a panel of monoclonal antibodies and revealed positivity for CD2, cytoplasmic CD3 (Fig. 3c), CD4 (Fig. 3d) CD7, and CD56 (Fig. 3e), as well as a negative stain for CD5, CD8, CD30, CD20, CD163, CD68 (Fig. 3f), programmed cell death (PD-1)/programmed cell death l ligand 1(PD-L1) (Fig. 3g ), and FoxP3. The neoplastic cells showed strong granular straining for the cytotoxic molecules granzyme B, perforin and TIA1(Fig. 3h). The immunostaining with a monoclonal antibody for the anaplastic lymphoma kinase (ALK) was negative. The molecular analysis of the T cell receptor gene was in a germline configuration. In situ hybridization for EBV-encoded small RNAs (EBERs) was strongly positive for most of the tumor cells (Fig. 3i). Histologic, immunophenotypic, genetic and clinical features consistent with the diagnosis of PC-ENKTL, nasal type. Despite the chemotherapy (dexamethasone, methotrexate, ifosfamide, L-asparaginase, and etoposide, SMILE) followed by radiotherapy was planned, she was going rapidly downhill and died of fetal infection 3 months after the onset of treatment.