The pyrrolo[1,2-a]benzimidazole (PBI) reductive alkylating agents have been investigated in this laboratory since their discovery in the late 1980s. Of all the structural modifications of the PBIs investigated so far, the variation of the 3-substituent has the greatest influence on cytotoxicity, toxicity, and in vivo antitumor activity. In the present study, we prepared both the R and S enantiomers of nitrogen-containing 3-substituents possessing hydrogen-bonding capability as well as varying basicity. The rationale was to take advantage of stereoselective DT-diaphorase reductive activation as well as hydrogen bonding in the DNA major groove. As a result of these studies, analogues were discovered possessing among the highest hollow fiber tumor assay scores observed in hundreds of natural and synthetic antitumor agents. Our findings indicate that a relatively basic 3-substituent is required for outstanding PBI cytotoxicity but that the importance of using pure enantiomers is still open to study.

No abstract

Axillary BCC is rare. Factors other than ultraviolet radiation likely contribute to the development of BCC, especially at sun-protected sites. Performing a periodic and complete cutaneous examination that includes sun-protected sites is important, especially in patients who have a history of skin cancer.

A 66‐year‐old woman was referred for evaluation of a rash on the leg. She had a 1‐year history of stage IV bronchogenic adenocarcinoma with previous metastases to the right first metatarsal‐phalangeal (MTP) joint and a left supraclavicular lymph node. She underwent six cycles of chemotherapy with paclitaxel (Taxol; Bristol‐Myers Squibb Company, Princeton, NJ, USA) and carboplatin (Paraplatin; Bristol‐Myers Squibb Company, Princeton, NJ, USA) as well as palliative radiation therapy to the metastasis sites. One month after completing radiation therapy, the patient developed a nonpainful rash on the right thigh. This eruption was treated as a herpes zoster infection by her internist with 3 weeks of valcyclovir (Valtrex; Catalytica Pharmaceuticals, Greenville, NC, USA), but without improvement. One month later the leg became painful and swollen and the rash spread up the thigh to involve the groin and vulva. The patient was referred to the dermatology department. Physical examination revealed multiple red, indurated, crusted papules and nodules involving the medial, anterior, and lateral right thigh, labia majora, and suprapubic area. The lesions were grouped and arranged in a dermatomal zosteriform distribution (Fig. 1). There was a visible peau d’orange appearance of the right leg with pitting edema. A punch biopsy showed irregular islands of atypical glandular epithelial cells infiltrating the superficial and deep dermis, consistent with metastatic adenocarcinoma (Fig. 2a). Immunohistochemistry showed positive staining to thyroid transcription factor (TTF) and cytokeratin 7 (Fig. 2b and c). The tissue did not stain with progesterone receptor, estrogen receptor, or gross cystic disease fluid protein (BRST‐2). This immunostaining pattern was identical to previous biopsies of the right first MTP joint and left supraclavicular lymph node metastases and is consistent with adenocarcinoma of the lung. 1 Eruption on the right thigh with grouped papules and nodules arranged in a zosteriform pattern 2 (a) Punch biopsy showing irregular islands of atypical glandular epithelial cells within the dermis (hematoxylin and eosin; original magnification × 100). (b) Positive staining with thyroid transcription factor (original magnification × 40). (c) Positive staining with cytokeratin 7 (original magnification × 40)

Lymphomatoid granulomatosis is a necrotizing angiocentric and angiodestructive infiltrative process involving primarily the lung, skin, central nervous system, and kidney. The incidence is highest in middle-aged men and is rare in children. We report a case of lymphomatoid granulomatosis involving both skin and lung in a 4-year-old boy. The disease progressed to peripheral T-cell lymphoma, which was unusual in light of recent evidence suggesting a B-cell origin in the majority of cases.