Barbara M. Egbert

Radiation injury of the normal and neoplastic prostate

Tissue samples from 40 patients with prostatic adenocarcinoma treated by radiation therapy were evaluated simultaneously by three observers to establish criteria for distinguishing residual tumor from radiation-induced atypia. Sections from 10 patients irradiated for nonprostatic pelvic neoplasms served as controls in addition to pretreatment biopsies from the determinate group. Patients had been treated by external x-irradiation, the majority receiving 6200–7400 rad to the prostate and pelvis over 7 to 8 weeks. Positive (tumor) biopsy incidence in the determinate group was 80% at 18 months, 40% at 36 months, and 43% in later samples. The following features were characteristic of radiation injury in the prostate: decreased ratio of the number of tumor glands to stroma, atrophy and squamous-like metaplasia of non-neoplastic glands with or without atypia, stromal fibrosis, arterial lumenal narrowing due to myointimal proliferation, foam cells within vessel walls, and fibrosis and atrophy of seminal vesicles. Criteria not useful for diagnosing radiation injury included architectural pattern or differentiation of tumor, cytologic features of tumor cells, inflammatory infiltrate, and ratio of normal glands to stroma. Ionizing radiation produced characteristic lesions in neoplastic and non-neoplastic prostatic glands, stroma, and blood vessels, and the sum of these changes was a reliable indicator of prior radiotherapy. An understanding of the morphologic effects of radiation injury of the prostate allowed distinction between residual prostatic adenocarcinoma and radiation-induced atypia of non-neoplastic glands.

Desmoplastic and spindle-cell malignant melanoma. An immunohistochemical study.

The clinical, histologic, and immunohistologic features of 22 desmoplastic melanomas (DMM), 10 mixed desmoplastic and spindle-cell melanomas (DMM/SMM), and two cellular spindle-cell melanomas (SMM) were studied. Patients ranged in age from 35 to 91 years (mean, 67) and included 23 men and 11 women. Seventeen cases occurred in sun-damaged skin of the head and neck. 11 were on the extremities, and six on the trunk. Except for two cases, all were Clarks level IV or V. Twenty-two (65%) cases were associated with a recognizable overlying pigmented lesion. Thirty of 32 (94%) DMM and DMM/SMM were clearly positive for S100. S100 staining was limited to < 5% of the spindle cells in two DMM/SMM. All DMM were negative when stained with HMB45. Three DMM/ SMM were immunoreactive with HMB45, as were both SMM. CD68 staining was limited to < 5% of the spindle cells in two of 32 DMM and DMM/SMM and 20% of the cells in one of two SMM. Nine (32%) DMM and DMM/SMM contained significant numbers of spindle cells immunoreactive for SMA but not desmin. In five cases, the number of actin-positive spindle cells. Two color stains for SMA and S100 demonstrated that these smooth-muscle actin positive cells constituted a separate spindle-cell population, consistent with reactive myofibroblasts. This study indicates that the immunohistologic features of desmoplastic melanoma differ from those of conventional melanoma. If a problematic spindle-cell skin lesion is a suspected melanocytic process, HMB45 is unlikely to provide confirmatory (or exclusionary) evidence for the diagnosis of DMM. Similarly, because of the variability in S100 expression in this neoplasm, the absence of S100 staining should not be relied on too heavily to exclude DMM if the clinical and histologic features favor that diagnosis. Caution should be exercised in the interpretation of numerous actin-positive spindle cells in isolation of additional confirmatory or exclusionary data as desmoplastic melanomas may contain significant numbers of these cells.

Desmoplastic malignant melanoma. A clinicohistopathologic study of 25 cases.

A clinical and histologic review of 25 patients with melanocytic lesions classified as desmoplastic malignant melanoma is reported. All of the lesions were located in sun‐exposed sites. The average age was 61.2 years (range, 38 to 83), with a median age of 56. There were 14 female and 11 male patients. Desmoplastic malignant melanoma is a melanocytic and fibroblastic proliferation that occurs predominantly in the head and neck area. The bland constituent cells resemble flbroblasts and are often arranged in bundles or fascicles, which may be arrayed perpendicularly to the overlying epidermis. Enlarged and/or atypical cells are usually scattered among the spindled cells. Most, but not all, of the tumors (24 of 25 in this series) are associated with lentigo maligna or an atypical junctional melanocytic proliferation. Mitotic figures are always found within the constituent cells of the fibrous‐appearing mass, and neurotropism may be present. Patients with desmoplastic melanoma typically present with a mass, which is occasionally associated with a pigmented lesion. The lesions in our series were deeply invasive to level IV or V. Lentigo maligna and a dermal fibroblastic‐appearing mass containing atypical cells arranged in fascicles are the most common morphologic features found in desmoplastic melanoma. Follow‐up data is available for 23 patients. The average length of follow‐up was 2.7 years (range, 0.1 to 9 years). Eighteen patients were observed for 3 or more years. Twelve patients developed local recurrences, and five developed metastases; three of the patients with metastases had a local recurrence before the development of metastases. Three of the patients with metastatic melanoma died of tumor between 2 and 4 years after their initial excision. Eight of the 12 locally recurring lesions were either diagnosed initially as a benign lesion or histologic examination was not performed on the initial excision specimen. It appears that recurrence may be related to inadequate initial therapy.

Cryolipolysis for noninvasive fat cell destruction: initial results from a pig model.

BACKGROUND Liposuction is one of the most frequently performed cosmetic procedures in the United States, but its cost and downtime has led to the development of noninvasive approaches for adipose tissue reduction. OBJECTIVE To determine whether noninvasive controlled and selective destruction of fat cells (Cryolipolysis) can selectively damage subcutaneous fat without causing damage to the overlying skin or rise in lipid levels. METHODS Three Yucatan pigs underwent Cryolipolysis at 22 sites: 20 at cooling intensity factor (CIF) index 24.5 (−43.8 mW/cm2), one at CIF 24.9 (−44.7 mW/cm2), and one at CIF 25.4 (−45.6 mW/cm2). Treated areas were evaluated using photography, ultrasound, and gross and microscopic pathology. Lipids were at various times points. One additional pig underwent Cryolipolysis at various days before euthanasia. RESULTS The treatments resulted in a significant reduction in the superficial fat layer without damage to the overlying skin. An inflammatory response triggered by cold‐induced apoptosis of adipocytes preceded the reduction in the fat layer. Evaluation of lipids over a 3‐month period following treatment demonstrated that cholesterol and triglyceride values remained normal. CONCLUSIONS Cryolipolysis is worthy of further study because it has been shown to significantly decrease subcutaneous fat and change body contour without causing damage to the overlying skin and surrounding structures or deleterious changes in blood lipids.

Effects of hyperthermia in a malignant tumor

The mechanisms of immediate and delayed tumor cell killing by hyperthermia were investigated in EMT‐6 neoplasms implanted in BALB/cKa mice. Radiofrequency electromagnetic fields were used to achieve a curative local dose of 44°C for 30 minutes. The tumors were sampled sequentially, during and after heat therapy, and studied by light and electron microscopy. Assays for cell survival, including cell cultures, were performed at various times after completion of therapy. Focal cytoplasmic swelling, rupture of the plasma membrane and peripheral migration of heterochromatin were observed 5 minutes after initiation of therapy and led to cytoplasmic fragmentation by the end of the treatment period (30 minutes). Necrosis of most cells occurred 2–6 hours after the end of treatment. At 48 hours, there were no recognizable tumor cells. A scar replaced the tumor bed 14 days later. Viable (clonogenic) tumor cells were still 2% of control levels at the end of therapy and then progressively decreased to 0.0003% at 48 hours, confirming the morphologic observations and indicating that factors other than the direct effect of heat on tumor cells contributed to complete tumor eradication. Our findings, coupled with previous studies, suggest that the immediate heat induced necrosis in this tumor occurs through the mechanisms of physical changes in the plasma membrane. The delayed (post‐therapy) cell death is likely due to modifications in the environment of the tumor bed.

Identification of herpes simplex virus DNA in lesions of erythema multiforme by the polymerase chain reaction

An association between erythema multiforme and herpes simplex virus infection has been supported by clinical studies and by the detection by immunofluorescence of herpes viral antigen in sera and skin biopsy specimens of patients with erythema multiforme. In rare cases, the virus has also been isolated in cultures of skin biopsy specimens of erythema multiforme. To investigate further the association between erythema multiforme and herpes simplex virus, we used the polymerase chain reaction for herpes simplex virus to examine skin lesions from patients with erythema multiforme. In this study herpes simplex virus DNA was detected in 11 of 31 biopsy specimens of erythema multiforme; six additional cases showed equivocal amplification results, which is suggestive of low amounts of viral DNA. Seven skin and mucosal biopsy specimens with the histologic changes of herpes virus infection served as positive controls: all were positive for herpes simplex virus DNA. Viral DNA was not detected in control biopsy specimens from skin excised for unrelated conditions. These studies support the association of herpes simplex virus in the pathogenesis of some cases of erythema multiforme. The polymerase chain reaction provides a quick and effective method of detecting herpes simplex virus in lesions of herpes-associated erythema multiforme. Furthermore, the polymerase chain reaction may delineate those cases of erythema multiforme that are etiologically related to herpes virus infection and therefore might be treated with acyclovir to prevent recurrence.

A case of argyria after colloidal silver ingestion

Background:  Argyria is often considered an entity of the past, one which has largely disappeared with the cessation of silver usage in oral medications. However, with the practice of colloidal silver ingestion in current “alternative health” treatments, argyria should be considered in the differential diagnosis of blue‐gray hyperpigmentation.

Pigmented spindle cell nevus. Clinical and histologic review of 90 cases.

A clinical and histologic review of 90 patients with melanocytic lesions termed pigmented spindle cell nevi (PSCN) is reported. The lesions are small in surface diameter, sharply confined both clinically and histologically, and often occur on the proximal extremities of young adults. They are generally of recent onset, moderately to heavily pigmented, and made up of nests of spindled cells confined to the epidermis and papillary dermis. There were 30 male and 60 female patients. Their average age was 25.3 years (ranging from 2.5 to 56 years). Lesions were located on the extremities in 61 cases (67%). Follow-up was possible in 38 cases seen more than 6 months after histologic diagnosis and ranged up to 40 months (average 14 months). No local recurrence or distant spread was found. The importance of recognizing this lesion lies in differentiating it from malignant melanoma. Conservative but complete excision has resulted in no recorded instances of local recurrence or distant spread

Effects of biopsy-induced wound healing on residual basal cell and squamous cell carcinomas: rate of tumor regression in excisional specimens

Background: Wound healing following a partial biopsy of basal cell (BCC) and squamous cell carcinomas (SCC) may induce tumor regression.

Histologic analysis of the thermal effect on epidermal and dermal structures following treatment with the superpulsed CO2 laser and the Erbium:YAG laser: An in vivo study†

To compare the in vivo histologic effects of the carbon dioxide (CO2) and erbium:yttrium aluminum garnet (Er:YAG) lasers. To ascertain the effects of combining CO2 and Er:YAG laser modalities during a single treatment session.