Extranodal NK/T‐cell lymphoma, nasal type, presenting after 5 years of remission

A 76‐year‐old woman with multiple edematous erythemas, erosions, and ulcers on the breast and abdomen was admitted to our hospital in June 2005. She had developed granulomatous bleeding lesions in the right nostril 6 years prior to her visit to our dermatology unit. She had been observed at the otorhinolaryngology department of our hospital, and a biopsy was taken from the nasal lesion. Computerized tomography and gallium scintigraphy ( 67 Ga single‐photon emission computed tomography) did not reveal any lesions corresponding to the diagnosis of malignant lymphoma. The histologic examination of the nasal specimen rendered a diagnosis of natural killer (NK)/T‐cell lymphoma, nasal. Because imaging analysis indicated a small‐sized tumor without metastases, oral prednisolone at 20 mg/day was administered for 1 month. The tumor decreased in size and disappeared after 19 months of low‐dose steroid therapy.  Five years after the initial treatment, the patient developed a fever of 38 °C with infiltrated erythemas and erosions on her breast. Erysipelas was initially suspected, but the antimicrobial agent did not show any effect and the multiple infiltrated erythemas and ulcers spread throughout her chest and abdomen ( Fig. 1). The lymph nodes were not palpable. The right nasal cavity showed no granulomatous lesions or other signs of abnormality. The peripheral white blood cell count (3000/µL), red blood cell count (3.54 × 10 6 /µL), and platelet count (112 × 10 3 /µL) were reduced. Atypical lymphocytes were not observed. The serum lactic dehydrogenase (LDH; 1770 U/L; normal, 224–454 U/L), aspartate aminotransferase (AST; 140 U/L; normal, 10–30 U/L), and alanine aminotransferase (ALT; 57 U/L; normal, 3–29 U/L) levels were elevated. The soluble interleukin‐2 (IL‐2) receptor level was high (25,300 U/mL; normal, 167–497 U/mL). Epstein–Barr virus (EBV) serologic examination showed the immunoglobulin G (IgG) viral capsid antigen (VCA) at 1 : 320 and the EBV nuclear antigen (EBNA) at 1 : 40. IgM VCA and EBV early antigen‐diffuse restricted antibody (EA) IgA and IgG were not detectable. Histologic findings from the left chest skin showed a distribution of atypical lymphocytes from the upper dermis to the subcutaneous tissue, and many foamy cells which had phagocytosed the hemocytes ( Fig. 2a,b). Immunohistochemical analysis showed that the atypical lymphocytes were sCD3–, CD4–, CD8–, CD20–, CD56+, granzyme B+, and T‐cell intracellular antigen (TIA‐1) positive. Furthermore, EBV‐encoded small RNAs (EBER), detected by in situ hybridization, exhibited a strong signal. The nasal lesions biopsied 6 years previously showed an identical staining pattern with the skin lesions immunohistochemically. Analysis of the T‐cell receptor‐β (TCR‐β), TCR‐γ, and TCR‐δ gene did not reveal any clonal rearrangements, but the EBV gene was detected from the skin specimens by Southern blotting. Our patient's condition was diagnosed as a case of extranodal NK/T‐cell lymphoma, nasal type, but the patient had concomitantly developed hemophagocytic syndrome (HPS). She was treated with a combination of steroid pulse therapy and chemotherapy (pirarubicin hydrochloride 30 mg/m 2 , cyclophosphamide 500 mg/m 2 , vincristine 1 mg/m 2 , prednisolone 30 mg/m 2 , etoposide 80 mg/m 2 ). After the first session of chemotherapy, the lesions on the chest and abdomen diminished, but, 2 weeks later, the skin lesions recurred, and disseminated intravascular coagulation (DIC) induced by HPS supervened. The patient died as a result of multiple organ failure induced by HPS. 1Multiple infiltrated erythemas, erosions, and ulcers on the breast and abdomen2Histologic findings of a skin biopsy specimen from the left chest (hematoxylin and eosin staining). (a) Dense infiltration of atypical lymphocytes from the upper dermis to the subcutaneous tissue (×40). (b) Many foamy cells had phagocytosed the hemocytes (×400)