Skin toxic effects of polyethylene glycol-coated liposomal doxorubicin.

OBJECTIVES: To record the profile of toxic effects of polyethylene glycol-coated liposomal doxorubicin hydrochloride (Doxil) to the skin, and to evaluate whether the long circulation pattern and enhanced accumulation of liposomes in specific skin sites will result in any unique presentations. DESIGN: Patients were accrued in the frame of dose-range-finding studies that examine the toxic effects and antitumor activity of Doxil therapy in metastatic breast and prostate cancers. All patients receiving Doxil were instructed to report any skin eruption or discomfort. Skin examination was performed on a regular basis at every cycle of Doxil therapy and after specific complaints. SETTING: Outpatient day care unit of the oncology institute of a secondary-referral medical center. PATIENTS: Sixty patients (45 women and 15 men). MAIN OUTCOME MEASURES: A basic severity scale of I through IV was adopted for toxic effects to the skin, based on National Cancer Institute common toxicity criteria. RESULTS: The following 4 patterns of skin eruptions were encountered: hand-foot syndrome (n = 24), diffuse follicular rash (n = 6), intertrigolike eruption (n = 5), and new formation of melanotic macules (n = 3). Another major toxic effect of Doxil was stomatitis, which was found to be the dose-limiting factor for the maximal single dose. Alopecia and extravasation injuries did not occur. CONCLUSIONS: The profile of toxic effects of Doxil to the skin reflects its unique pharmacokinetics and tissue distribution. These skin reactions vary significantly from those associated with doxorubicin in non-liposome-encapsulated form.

Nedocromil sodium ameliorates skin manifestations in a murine model of chronic graft-versus-host disease.

Dermal fibrosis, loss of cutaneous appendages, and loss of subcutaneous fat are the main manifestations of chronic graft-versus-host disease (cGVHD) in mice. Mast cells (MC) may have a role in cGVHD. To investigate this point we have evaluated the effect of a MC stabilizer (nedocromil sodium) and a MC activator (compound 48/80) on skin manifestations in a murine model of cGVHD (B10.D2-->BALB/c). Mice were treated with nedocromil sodium (5 mg/day) or compound 48/80 (10 micrograms/day) from day -3 until day 15. Nedocromil ameliorated the skin features of cGVHD while compound 48/80 caused skin changes reminiscent of mild cGVHD in control mice. In addition nedocromil normalized peritoneal MC numbers and skin MC numbers and their activation state in the cGVHD mice. On the other hand compound 48/80 caused a complete disappearance of toluidine blue stainable peritoneal MC from cGVHD and control mice and decreased skin MC in controls. In summary, MC activation may play a negative role in the skin changes seen in cGVHD while MC stabilization ameliorates the skin manifestations of cGVHD and therefore may have a therapeutic benefit.

Total leucoderma: a rare manifestation of cutaneous chronic graft-versus-host disease.

We describe a 14-year-old boy who developed total leucoderma during the course of chronic graft-versus-host disease, which developed after allogeneic bone marrow transplantation. Skin biopsy and dihydroxy-phenylalanine staining revealed a total absence of melanocytes from the epidermis. Cytotoxic anti-melanocyte antibodies were found in the patient's serum, and this probably explains the development of the leucoderma.

Generalized granuloma annulare post autologous bone marrow transplantation in a Hodgkin's disease patient.

A case of generalized granuloma annulare is described in a patient with Hodgkin's disease 3 weeks after autologous bone marrow transplantation (BMT). This is, to our knowledge, the first report of generalized granuloma annulare post-BMT. Immunological pathogenesis is suggested and the association with delayed-type hypersensitivity reaction is discussed.

Follicular mycosis fungoides.

Follicular mycosis fungoides is a rare variant of cutaneous T-cell lymphoma. We report a patient with thin plaques of mycosis fungoides studied with follicular papules. Histologically, these lesions were composed of dense infiltrates of lymphocytes within and around follicular epithelium ("folliculotropism"). This case indicates that follicular mycosis fungoides is a distinct clinicopathologic entity. It is different from follicular mucinosis associated with mycosis fungoides. Conceptually, the relationship between follicular mycosis fungoides and ordinary mycosis fungoides is analogues to the relationship of lichen planopilaris to ordinary lichen planus.

Local cutaneous reaction induced by subcutaneous interleukin-2 and interferon alpha-2a immunotherapy following ABMT.

Immunotherapy using subcutaneous injections of recombinant interleukin-2 (IL-2) and recombinant interferon alpha-2a (IFN-alpha) for advanced hematologic and solid tumors is rapidly developing. We report five patients with Hodgkin's and non-Hodgkin's lymphoma who developed a local cutaneous reaction consisting of inflammatory painful nodules with a central multiloculated vesicle at the site of sc injections of IL-2 and IFN-alpha immunotherapy following ABMT. This is the first report of a local cutaneous adverse reaction induced by IL-2 and IFN-alpha immunotherapy following ABMT.

Merkel cell tumor masquerading as granulation tissue on a teenager's toe.

Merkel cell tumor (MCT) typically occurs on the head or neck of elderly patients. A case is presented of a teenage girl with an MCT on her toe. The diagnosis was made 5 years after an ingrown nail on the toe was avulsed. During the interim 5 years, the periungual skin looked like granulation tissue and thus no biopsy was performed. This case of MCT is unique in three aspects: (a) extraordinarily young age, (b) atypical site, and (c) deceptive clinical appearance. Awareness of the possible occurrence of MCT in younger patients and in unusual locations will facilitate earlier diagnosis.

Rapid whitening of the hair first reported in the Talmud. Possible mechanisms of this intriguing phenomenon.

The first reported episode of rapid whitening of the hair is recorded in the Talmud. This intriguing phenomenon is explained on the basis of a two-step process. The first step involves the actual abrupt development of white hair due to vitiligo or alopecia areata. The second step involves the apparent sudden whitening of the scalp hair due to either simultaneous lengthening of the white hair or selective loss of the dark hair. In fact, the hair that is perceived as suddenly whitening was already white.

Genital lentiginosis: a clinical and histopathologic study.

We studied the clinical and histopathologic characteristics of melanotic macules of the penis and vulva. The 10 lesions studied were relatively large (up to 2 cm), multifocal, irregular in outline, and had variegated pigmentation. Most were regarded as clinically atypical in appearance. Histologic examination of the lesions showed basal layer hyperpigmentation, slight melanocytic hyperplasia, epithelial hyperplasia, and stromal melanophages. No cytologic atypia of melanocytes was detectable. Information is insufficient at present to predict the natural history of genital lentiginosis or its relation to mucocutaneous melanoma.

Elastophagocytosis: a non-specific reaction pattern associated with inflammatory processes in sun-protected skin.

Four cases characterized by primary inflammatory processes localized to sun-shielded skin were observed to have associated phagocytosis of elastic fibers by multinucleate histiocytic giant cells. These findings support the idea that this reaction pattern may occur non-specifically, at least in some instances, in sun-protected areas, as well as in sun-exposed skin as previously reported.

Malignant blue nevus. Case report and literature review.

A well-documented case of malignant blue nevus is presented, along with an in-depth review of the literature. Malignant blue nevus is a rare form of malignant melanoma. A cellular blue nevus is the precursor lesion. The scalp is the most common site. The tumor often presents clinically as a progressively enlarging or multinodular blue-black lesion. The histologic pattern is fascicular dense collections of pigmented, pleomorphic spindle cells. Because of marked regional histologic variation within a malignant blue nevus, however, sampling error can cause delay in recognition of malignancy. A high clinical index of suspicion and appropriate biopsy technique are necessary to reach an early diagnosis. The most common site of metastasis of a malignant blue nevus is the lymph node. The phenomenon of benign lymph node nevus cell metastasis, which may occur with benign blue nevi, must be differentiated from a true malignant metastasis of a malignant blue nevus.

Documented evolution of a solar lentigo into a solitary lichen planus-like keratosis.

The purpose of this communication is to report the evolution of a solar (senile) lentigo into a solitary lichen planus-like keratosis (SLPLK). This case is unique because this evolution was documented by biopsies taken from the same lesion nearly 5 years apart. The pathogenesis of SLPLK is discussed.

Invasive squamous cell carcinoma initially diagnosed as a giant keratoacanthoma.

Keratoacanthoma (KA) is currently considered a benign epithelial neoplasm. We report a patient with a lesion diagnosed as a KA that behaved aggressively like a squamous cell carcinoma (SCC). Similar reports are not uncommon in the literature. Because there are currently no criteria by which KA can be differentiated from SCC in all instances, we prefer to group KAs within the spectrum of well-differentiated SCC. We emphasize excisional surgery as the treatment modality of choice.