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Notes: A 48-year-old woman presented with extensive facial ulceration of 1 year in duration. Based on the combination of the clinical appearance and a “nondiagnostic” biopsy taken elsewhere, the patient was started on oral prednisone at a dose of 40 mg/day, with a working diagnosis of pyoderma gangrenosum. According to the patient, the ulceration worsened over the 2 months whilst on prednisone and pain control was a major issue, controlled for the most part with oral oxycodone. One month prior to our evaluation of the patient, she was started on dapsone at 50 mg/day with no added benefit. Approximately 2 years prior to our evaluation, she developed raised, reddish, skin lesions on the abdomen and legs which recurred, but healed spontaneously each time after a few weeks.Her past medical history was remarkable for the remote use of intravenous drugs (which she had stopped for the past 20 years) and the past and continued use of alcohol on a daily basis. She had recently been tested elsewhere and was found to be positive for hepatitis C, but not human immunodeficiency virus (HIV). Examination revealed several ulcerations of the face and forehead, with an “apple jelly” coloration to the periphery and necrotic center. There was complete erosion of the nasal sidewall with apparent involvement of the septum (〈link href="#f1"〉Fig. 1). There were also scattered, smaller, nonulcerated, reddish to purplish lesions on the abdomen. Otolaryngologic examination revealed ulceration of the right ala and erosion of the nasal septum, but was otherwise unremarkable. No cervical or submental lymphadenopathy was noted.〈figure xml:id="f1"〉1〈mediaResource alt="image" href="urn:x-wiley:00119059:IJD2035:IJD_2035_f1"/〉Facial ulceration at the time of initial evaluationRoutine laboratory tests showed the patient to be anemic, with a hemoglobin level of 11 g/dL (normal, 12–15.5 g/dL) and a white blood count of 13,300 (normal, 3500–10,500) The total bilirubin was normal at 1.0 mg/dL, but several liver function tests were elevated by 2–4 times the upper limit of normal, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), and γ-glutamyl transpeptidase (G-GT). Hepatitis C tests were abnormal, including antibody to hepatitis B core antigen (anti-HBc) and anti-hepatitis C virus (anti-HCV) antibodies, and hepatitis C-RNA was positive. Anti-hepatitis B surface antigen (anti-HBsAg) and antibody were negative. Human immunodeficiency virus (HIV) was negative. Antinuclear antibodies, antineutrophil cytoplasmic antibodies (ANCA), serologic tests for syphilis, cryoglobulins and cryofibrinogens, renal function, and urinalysis were all either negative or normal. The chest X-ray showed bilateral pulmonary nodules, confirmed by computed tomography (CT) scan of the chest. Serologic tests for several fungal organisms, including Sporothrix and Cryptococcus, were negative. Tuberculin skin testing was negative.Two 4-mm punch biopsies were taken from the right cheek and from the right lower lateral abdomen near the hip. Biopsy of facial tissue cultures for acid-fast bacilli and fungal elements was negative. Bacterial culture revealed 1+Staphylococcus aureus and coagulase-negative Staphylococcus. Polymerase chain reaction (PCR) testing for herpes and varicella viruses was negative.Histologic examination of the skin biopsies revealed identical findings from both sites. There was parakeratosis, serum crust, and mild irregular epidermal acanthosis. Focal interfacial dermatitis was present and characterized by basal vacuolization and melanophages in the superficial dermis. Epidermotropism of atypical lymphocytes singly and in cell clusters was seen in the epidermis. In the papillary and reticular dermis, extending to the subcutaneous fat, there was a dense, diffuse, perivascular, interstitial, and periappendageal infiltrate composed of atypical lymphocytes, lymphocytes, histiocytes, plasma cells, and neutrophils. The atypical lymphocytes infiltrated the hair follicles with little associated spongiosis (pilotropism) (〈link href="#f2"〉Fig. 2). The atypical lymphocytes also surrounded and infiltrated the eccrine glands and blood vessels. Immunoperoxidase studies were performed on paraffin tissue and showed that the atypical lymphocytes were immunoreactive with CD3 (〈link href="#f3"〉Fig. 3) and βF1, but not with CD8, CD56, T-cell-restricted intracellular antigen-1 (TIA-1), or granzyme B. There was a reactive population of B lymphocytes immunoreactive with CD20. In situ hybridization for Epstein–Barr virus (EBV), performed on paraffin sections, was negative. Lung biopsy of several nodules was accomplished via video-assisted thoracoscopy and revealed a peripheral T-cell lymphoma. Gene rearrangement studies of skin and lung nodules showed similar T-cell clones and were positive for T-cell rearrangement by PCR (TCR PCR, T γ-chain positive).〈figure xml:id="f2"〉2〈mediaResource alt="image" href="urn:x-wiley:00119059:IJD2035:IJD_2035_f2"/〉Histopathology of a skin lesion. (a) Dense atypical lymphocytic infiltrate demonstrating pilotropism and epidermal involvement with little associated spongiosis (hematoxylin and eosin stain, × 200). (b) Higher power view better demonstrating the dense atypical lymphocytic infiltrate (hematoxylin and eosin stain, × 400)〈figure xml:id="f3"〉3〈mediaResource alt="image" href="urn:x-wiley:00119059:IJD2035:IJD_2035_f3"/〉Strong CD3 immunoreactivity of the infiltrate (CD3 stain, × 200)The final diagnosis was peripheral T-cell lymphoma with pulmonary and skin involvement. There was no evidence for EBV infection.The patient returned home to receive treatment with four cycles of hyper-CVAD (cyclophosphamide, vincristine, adriamycin, and dexamethasone), followed by autologous stem cell transplantation. The facial erosions and ulcerations, as well as the systemic nodules, responded well to therapy, with only limited recurrence of the right lower lateral abdominal lesions, which were subsequently treated with radiation (〈link href="#f4"〉Fig. 4). The patient's clinical status 18 months after treatment is complete remission from lymphoma, but she has developed fulminant liver failure secondary to cirrhosis associated with hepatitis C.〈figure xml:id="f4"〉4〈mediaResource alt="image" href="urn:x-wiley:00119059:IJD2035:IJD_2035_f4"/〉Facial lesions after completion of chemotherapy

Notes: Summary Piroxantrone is an anthrapyrazole compound undergoing phase II testing in a variety of diseases. The anthrapyrazoles are a series of compounds synthesized with the intent of maintaining the broad antitumor activity of anthracyclines, but with lessened cardiac toxicity. The Southwest Oncology Group (SWOG) conducted a phase II trial of piroxantrone in advanced soft tissue sarcoma. Treatment consisted of piroxantrone 150 mg/M2 administered intravenously over 1 hour every 21 days. Twenty-five eligible patients were registered to the trial. Twenty-three patients received treatment and are fully evaluable for response and toxicity. Two partial responses were seen for an overall response rate of 9% (95% confidence limit 1%–28%). Abnormal cardiac ejection fraction occurred in five patients, and fatal congestive heart failure developed in one patient on study. Toxicities other than cardiac were tolerable. Based on the observed response rate and cardiac toxicity, further trials of piroxantrone in the treatment of soft tissue sarcoma do not appear warranted.

Notes: Summary A phase I trial of chlorozotocin was completed for a weekly times four dose schedule repeated every 8 weeks. Thrombocytopenia was the acute dose limiting toxicity. Nausea and vomiting were moderate to severe and dose related. Two cases of possible drug related irreversible nephrotoxicity were seen. Transient elevations of serum creatinine and mild proteinuria were noted. Also, transient elevations in SGOT were observed. One patient with a carcinoid tumor had a 60% reduction in his 5HIAA level after one course of therapy. The recommended dose for phase II clinical studies of chlorozotocin is 40 mg/m2 IV weekly for four weeks, repeated every 8 weeks.

Notes: Summary A Phase I trial of AT-125 was completed for the bolus dose every three week schedule. Dose limiting toxicity was primarily central nervous system (CNS) in the form of ataxia, confusion, hallucinations and dysarthria. Although this was most severe at doses of 150 mg/m2, lesser symptoms were reported at all dose levels. Nausea and vomiting were moderate to severe at higher doses. Myelosuppression did not occur. This schedule is not recommended for Phase II studies until methods are developed to reduce drug-related CNS toxicity.