Doru T. Alexandrescu

Fatal intra-alveolar hemorrhage after rituximab in a patient with non-Hodgkin lymphoma.

A 65-year-old male developed progressive dry cough and digital clubbing after starting rituximab-CHOP chemotherapy for non-Hodgkin lymphoma. A lung biopsy showed loose non-necrotic granulomas in a background of mild fibrosis and rare eosinophils, compatible with a drug-induced hypersensitivity pneumonia. Associated manifestations of this hypersensitivity reaction were a high eosinophil count, elevated serum levels of immunoglobulin E, and a skin rash consistent with pigmented purpuric dermatitis (Schamberg disease). Corticosteroids were marginally efficacious in treating this reaction. Few similar reactions have since been described, 2 of them ultimately fatal, but none was associated with pulmonary hemorrhage. A 2.5 : 1 ratio between the interstitial alveolar T4/T8 lymphocytes in our case is similar to the findings in methotrexate-induced pneumonitis and farmer lung disease. This report documents the serologic and immunohistologic findings associated with a pulmonary interstitial reaction to rituximab. A review of the pertinent literature is provided. The possible pathogenetic mechanisms, including the role of cytokines, cytotoxic T-lymphocytes and CD 20 positive T-cells in relation to the administration of rituximab are discussed.

Chemotherapy‐induced scleroderma: a pleiomorphic syndrome

A scleroderma‐like disease has recently been described in association with taxanes. We present the first case of diffuse scleroderma occurring in a woman treated with doxorubicin and cyclophosphamide for breast cancer. The clinical pattern of skin involvement and histological alterations were identical to those found in the classical form of scleroderma. Skin involvement progressed to affect 80% of total body area, and subsequently remained unchanged despite progression of the underlying cancer, making a paraneoplastic aetiology of the scleroderma unlikely. Specific chemotherapeutic agents might be directly responsible for the clinical manifestations and the parameters of progression. Analysis of all similar case reports defines the particular features and clinical course of this phenomenon.

Unusual cutaneous involvement during plasma cell leukaemia phase in a multiple myeloma patient after treatment with thalidomide: a case report and review of the literature

We report the case of a 54‐year‐old African–American male with IgG multiple myeloma (MM) with disease resistant to multiple chemotherapy regimens and immunomodulatory treatment with thalidomide. In spite of achieving a partial remission of short duration, his disease accelerated to peripheral plasmacytosis and subsequent development of cutaneous plasmacytomas. The malignant plasma cells derived from the dermal lesions were CD45+, CD38+, CD138+ and matched the immunophenotype of the plasmacytes during the leukaemic phase. Occurrence of extramedullary lesions in the setting of MM treated with thalidomide is of concern, although currently there are very few reports describing this association. We discuss the possible relationship between the patients unusual disease course and the administered chemo‐ and immunotherapy. The significance of the changes in adhesion molecules, especially CD 138 and CD 56, relevant to the development of cutaneous plasmacytomas is discussed.

Anticipation in families with Hodgkin's and non-Hodgkin's lymphoma in their pedigree

Anticipation is an earlier onset and/or increasing severity in successive generations. This study was conducted to determine whether anticipation occurs in families that exhibit both Hodgkins (HD) and non-Hodgkins (NHL) lymphoma in their pedigrees. Nine published reports of multi-generational lymphoma and 33 previously unreported families with both lymphomas were analysed for evidence of anticipation. The difference between age at onset for each affected related pair was tested against the null hypothesis that there is no difference in age at onset. Differences between disease-free survival in affected generations were determined. These analyses were also conducted separately using only parent – child pairs with an age of onset above 25 years in an effort to avoid ascertainment bias. Age at onset in studied cases was also compared with the HD and NHL series from the Surveillance Epidemiology and End Results (SEER) Program of the US National Cancer Institute. The mean age at onset in the child and parent generations of all case families (60.2 and 35.7 years, respectively) and in the selected pairs (61.5 and 45.6, years) were significantly different (mean difference −24.5 years; P < 0.00001, and −15.9 years, P < 0.00001, respectively). Mean anticipation for parents with HD and children with NHL was −6.8 years (P = 0.01) for the unpublished and −14.4 years (P = 0.002) for the published families (overall anticipation −10.1 years). Mean anticipation for parents with NHL and children with HD was −34.4 years (P < 0.0001) for the unpublished and −32.7 years (P < 0.0001) for the published families (overall anticipation −34.2 years, P < 0.0001). The signed rank test rejected the null hypothesis which stated that there was no difference in age at onset between parents and children for overall, as well as selected pairs (P < 0.00001). The null hypothesis was also rejected for both the parents with HD/children with NHL group and the parents with NHL/children with HD group pairs (P < 0.0001). Age at onset distributions were significantly different for all generations with HD or NHL when compared to the SEER population (P < 0.00001), except for the parents with NHL, which showed no difference. In addition, this study reports four previously unpublished families with three generations of lymphoma in their pedigrees. These data suggest that anticipation occurs in families that exhibit both HL and NHL and that both neoplasms may have a common genetic basis.

Mitoxantrone, vinblastine and CCNU: Long-term follow-up of patients treated for advanced and poor-prognosis Hodgkin's disease

Advanced-stage or relapsed/refractory Hodgkins disease (HD) has a poor prognosis despite aggressive chemotherapy regimens and the use of high-dose therapy with autologous stem cell support. Mitoxantrone, vinblastine and CCNU (lomustine) (MVC) combines the most effective chemotherapeutic agents of previous regimens for poor prognosis HD, and eliminates marginally active agents with unnecessary toxicities, such as bleomycin and dacarbazine. Sixty-eight patients with HD (23 newly diagnosed and 45 with relapsed/refractory disease, one patient treated both de novo and years later in relapse) were treated with the MVC regimen (mitoxantrone 8 mg/m2/day i.v. days 1 – 3; vinblastine 8 m/m2/day days 1 and 22; and CCNU (lomustine) 100 mg/m2 on day 1, repeated at 6 – 8 weeks) in a single-arm Phase II study. All patients responded to treatment in the newly diagnosed group (overall response = 100%). The median response duration was not reached, but was in the range 7.6 – 180 + months, and median survival was 94 months. Eleven complete responses are ongoing at 39 – 180 + months. In the previously-treated patients, 41 responded to MVC (OR = 91%). The median response duration for this group was 11 months, and the median survival was 34 months after initiating MVC. Four secondary myeloid leukemias occurred, three in de novo, and one in the relapsed/refractory group, at a median follow-up of 14 years. MVC regimen for HD is highly active, for both de novo and relapsed/refractory disease, with high response rates and survival that compare favourably with the results obtained by high-dose therapy with stem-cell transplantation. Although significant, the toxicities associated with this regimen were manageable.

Trastuzumab/docetaxel‐induced nail dystrophy

Combination of trastuzumab, an antibody directed against the Her‐2/neu receptor, with chemotherapy is increasingly used for the treatment of metastatic breast cancer, and currently is being explored in the adjuvant setting. We report the case of a 55‐year‐old woman with metastatic breast cancer, who developed nail dystrophic changes comprising Beaus lines, subungual hyperkeratosis, dyschromia and onycholysis early in the treatment with trastuzumab/docetaxel. Nail alterations advanced with the continuation of therapy. This combination of nail changes, and its progressive course, are extremely rarely encountered with the use of taxanes alone. The cellular mechanisms of action of trastuzumab and docetaxel are discussed in regards to their potential synergy, which may explain the particularities and severity of nail alterations in this patient.

Metastatic choriocarcinoma in a middle-aged man presenting as a right thigh mass with venous thrombosis: a case report.

Choriocarcinoma is a highly aggressive β-subunit of human chorionic gonadotropin (βHCG)-producing germ cell tumor. In men, it is a rare neoplasm and can arise in the testes or in various extragonadal locations such as the retroperitoneum, mediastinum, and pineal body. We present a highly unusual case of a middle-aged man with primary metastatic βHCG-producing choriocarcinoma of the right thigh along with right lower-extremity venous thrombosis. We comment on prognostic variables as well as discuss several theories to account for the unusual location of his choriocarcinoma.