Melanoma mimicking dermal and Spitz's nevus ("nevoid" melanoma)

We describe two examples of malignant melanoma that present with clinical and histopathologic characteristics resembling the benign acquired dermal nevus and the spindle and epithelioid cell nevus (Spitz's nevus), respectively. Both lesions were present on the trunk of adult patients. The clinical impression in both cases was dermal nevus. Histopathologically, these lesions were fairly well circumscribed and symmetrical; they exhibited an expansile dermal proliferation of atypical nevomelanocytes in nests and fascicles with only minimal intraepidermal involvement. These lesions which we will designate as "nevoid" melanoma can be misinterpreted as benign nevi because of the absence of prominent intraepidermal pagetoid spread and the pattern of apparent dermal maturation at the base of the tumor associated with a gradual diminution of cell size. These features mimic the maturation phenomena in banal dermal nevi and spindle and epithelioid cell nevi. The differential diagnosis includes other types of melanoma, and various benign entities characterized by a predominantly dermal proliferative process, such as deep penetrating nevus and cellular neurothekeoma. The recognition of nevoid melanoma is critical so that patients with these lesions receive appropriate therapy for malignant melanoma.     

'Tubular' epithelioid cell nevus: a new variant of Spitz's nevus

The term Spitz's nevus refers to a large spectrum of nevi composed of spindle and/or epithelioid cells. We report on a hitherto undescribed tubular variant of a dermal epithelioid nevus, characterized by aggregates composed exclusively of cuboidal cells with the prominent feature of tubular or microcystic structures. Immunohistochemically, the epithelioid cells expressed melanocytic markers (S-100, NKI/C3) lacking markers for cytokeratin or carcinoembryonic antigen. The three-dimensional analysis of the lesions by confocal laser scanning microscopy revealed the structural configuration of tubular or microcystic empty spaces bordered by cuboidal nevus cells. This rare variant of epithelioid nevus is another example for the remarkable diversity of Spitz's nevi.     

Benign juvenile Spitz melanoma in a dermal nevus cell nevus in an adult. Molluscum contagiosum on a dermal nevus cell nevus

A patient with a cancer of the colon or rectum is at increased risk for developing subsequent cancer of his remaining large bowel, particularly when associated polyps and papillomas are present, and when the initial resection is for two or more growths. Patients who develop signs and symptoms of large-bowel tumors following colonic resections for carcinoma should be completely evaluated for another primary tumor. If it is assumed that these patients simply have recurrences of their initial cancers and therefore they are not treated, many patients would be denied a potentially curative operation. All investigators agree that this group warrants long-term follow up, ideally with regular and double-contrast enema studies and sigmoidoscopy. Earlier diagnosis of a second colorectal cancer should improve the resectability rate and prognosis. Those patients with intact cell-mediated immunologic responses seem to do better after surgical treatment.     

Tumor vascularity, proliferation, and apoptosis in human melanoma micrometastases and macrometastases

BACKGROUND: Clinically undetectable or dormant metastases (micrometastases) probably account for disease recurrence, ie, clinically evident metastases, in patients after disease-free intervals of variable length. Recently developed animal models have shown that dormancy may potentially be explained by the fact that these micrometastases are not vascularized and have comparable rates of cellular proliferation and programmed cell death (apoptosis), enabling them to remain viable indefinitely but not to show progressive growth. OBSERVATION: We report for the first time that melanoma micrometastases from humans are similarly not vascularized (mean number of microvessels, 10.2), have significantly lower rates of tumor cell proliferation (mean, 2.4%), comparable rates of proliferation and apoptosis (means, 2.4.% and 0.2%, respectively), compared with melanoma macrometastases, which have significantly greater tumor vascularity (mean number of microvessels, 18.7), higher rates of proliferation (mean, 18%), and higher rates of proliferation relative to apoptosis (means, 18% vs 1.6%). Tumor vascularity was quantified using the lectin Ulex europaeus agglutinin I to identify the number of microvessels per unit area (microscope ocular grid with an area of 7.84 x 10(-2) mm2 at x400 magnification). Melanoma cell proliferation rate was assessed with the MIB-1 antibody (Ki-67) as the number of positive nuclei per total number of tumor nuclei counted at x400 magnification. Apoptosis was quantified using the method of terminal deoxynucleotidyl transferase-medicated deoxyuridine triphosphate-biotin nick end labeling. The number of positive nuclei were quantified per total number of tumor nuclei; usually 200 tumor nuclei were counted at x400 magnification. CONCLUSION: We report, for the first time, that human micrometastases demonstrate attributes, ie, the lack of significant tumor vascularity and low but comparable rates of proliferation and apoptosis, that may explain the dormant state.     

Diagnosing and treating congenital melanocytic nevus simulating malignant melanoma

Many cases reported as malignant melanomas arising in benign congenital melanocytic nevi in the neonatal period have not shown evidence of metastases after several years of follow-up. These lesions were probably pathologically misdiagnosed, thus creating a controversy regarding the precise incidence. This article describes the case of an infant with a giant melanocytic nevus simulating malignant melanoma to illustrate the proper criteria for diagnosis of this condition so extensive and unnecessary therapy procedures can be avoided.     

Hypermutability of UV-treated plasmids in dysplastic nevus/familial melanoma cell lines

Members of cutaneous melanoma (CM) families with dysplastic nevi (DN) are at high risk of developing CM. Using a shuttle vector plasmid, pSP189, cell lines from three patients with CM plus DN were previously found to have elevated post-UV plasmid mutability. To investigate familial occurrence of this cellular phenotype, we examined post-UV plasmid mutability in 31 lymphoblastoid cell lines from 6 familial CM kindreds. In comparison to 16 normal control lines, we found an abnormally elevated post-UV plasmid mutability in cell lines from 13 of 13 patients with CM plus DN (P = 1.5 x 10(-8)) and from 5 of 8 patients with DN only (P = 0.001). Elevated spontaneous plasmid mutation frequency (MF) was also present in cell lines from six of the CM plus DN patients (P = 0.002) and three of the DN-only patients (P = 0.028). However, cell lines from two patients with CM without DN had normal post-UV plasmid MF. Although not specific for CM patients, of 27 cell lines with elevated post-UV plasmid MF, only 8 were from donors who did not have CM + DN or DN (19 of 24 versus 8 of 28; P = 0.0003). This study indicates that post-UV plasmid hypermutability is a laboratory marker for members of melanoma-prone families and suggests that patients with familial CM have a defective mechanism for handling UV-induced DNA damage.     

Coincidence of balloon cell melanoma with balloon cells in a dermal nevus]

OBJECTIVE: To determine the effects of megestrol acetate on testosterone, dehydroepiandrosterone and PSA levels in patients with disseminated prostatic carcinoma. METHODS: 26 patients with disseminated prostatic carcinoma treated with megestrol acetate were followed for 21 months to determine its effects on testosterone, dehydroepiandrosterone and PSA levels. RESULTS/CONCLUSIONS: We observed a testicular and adrenal antiandrogenic effect. Patient clinical course improved when PSA levels dropped, although this improvement was not related with changes in androgen levels.     

Evidence for nodular epileptogenicity and gender differences in periventricular nodular heterotopia

The new synthetic oleanane triterpenoid 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid (CDDO) is a potent, multifunctional molecule. It induces monocytic differentiation of human myeloid leukemia cells and adipogenic differentiation of mouse 3T3-L1 fibroblasts and enhances the neuronal differentiation of rat PC12 pheochromocytoma cells caused by nerve growth factor. CDDO inhibits proliferation of many human tumor cell lines, including those derived from estrogen receptor-positive and -negative breast carcinomas, myeloid leukemias, and several carcinomas bearing a Smad4 mutation. Furthermore, it suppresses the abilities of various inflammatory cytokines, such as IFN-gamma, interleukin-1, and tumor necrosis factor-alpha, to induce de novo formation of the enzymes inducible nitric oxide synthase (iNos) and inducible cyclooxygenase (COX-2) in mouse peritoneal macrophages, rat brain microglia, and human colon fibroblasts. CDDO will also protect rat brain hippocampal neurons from cell death induced by beta-amyloid. The above activities have been found at concentrations ranging from 10(-6) to 10(-9) M in cell culture, and these results suggest that CDDO needs further study in vivo, for either chemoprevention or chemotherapy of malignancy as well as for neuroprotection.     

Epidermal nevus and rhabdomyosarcoma

A child with an epidermal nevus was diagnosed at the age of 15 months as having an embryonal rhabdomyosarcoma of the bladder. This child also had pigmentary abnormalities characteristic of the epidermal nevus syndrome. The question is again asked whether patients with epidermal nevi have an increased incidence of tumors. It is suggested that the thorough evaluation of these patients as recommended by Solomon should also include an alertness for the development of earlier-than-anticipated neoplasms.     

Recipient bed vascularity and the survival of ischaemic flaps

The purpose of this study was to identify the length of the ischaemic period required to induce the 'no-reflow' phenomenon in a rat epigastric flap on an avascular recipient site. The vascularity of the recipient bed may affect flap survival in the early postischaemic stage after flap transfer. Initially, we designed epigastric flaps in 300-350 g Sprague-Dawley rats and separated the rats into four groups of 5 rats each (total 20 rats). In groups 1, 2, 3, the flaps were made ischaemic for 1 hour, 6 hours and 10 hours, respectively, by temporarily clipping the epigastric artery and vein. In group 4, the epigastric artery and vein were divided to create permanent ischaemia. In groups 1, 2 and 3, ischaemia was ended by removing the clips. After the ischaemic flaps were reperfused, their viability was studied by measuring the flap survival rate at postoperative day 7. Flap survival was studied by direct observations, laser Doppler flowmeter measurement of flap blood flow, histopathology, and carbon particle perfusion of the flap vasculature. Ischaemic flaps of groups 1 and 2 recovered almost completely after reperfusion due to the short period of ischaema. In a second series of experiments, in order to evaluate the contribution to flap survival of the recipient vascularised bed, another four groups of epigastric flaps (of 5 animals each, using the same time periods as above) were raised and a piece of Biobrane was interposed between the flap and the recipient bed before the flap wound was closed, to eliminate all nutrient supply from the recipient bed. THe results showed that the combined effect of the reperfused flap vasculature plus the metabolic contribution of the recipient bed significantly (P < 0.01) increased the extent of flap survival of the 6- and 10-hour ischaemic flaps as well as the divided pedicle flaps, which were never reperfused. An absolute 'no-reflow' rat model flap for further flap salvage studies was also developed.     

Tumor vascularity predicts recurrence in differentiated thyroid carcinoma

Insulin treatment is reportedly associated with the transient progression of retinopathy, possibly with the development of macular oedema in middle-aged Type 2 diabetic patients. The purpose of this study was to investigate the effect of insulin treatment on eye-grounds in elderly (> 65-year-old) Type 2 diabetic patients with secondary failure of oral antidiabetic-drug therapy. Eye examinations were performed in 37 patients randomized to insulin (n = 19) or sulphonylurea (n = 16) treatment and re-investigated after one year. Insulin treatment reduced HbA1c from 9.3% to 7.3% (p < 0.001) after one year. In the sulphonylurea-treated group, HbA1c did not change (9.1 vs. 9.3%). At the start, 65% of the patients had retinopathy, and after one year progression was noted in 7/35 patients (20%; 5 insulin- and 2 sulphonylurea-treated). In the insulin-treated group, the 5 patients with progression had higher initial fasting blood-glucose levels than other patients in the group (15.8 vs 13.1 mmol/L, p < 0.05). Initial HbA1c levels did not differ between the groups (9.8 vs. 9.1%, n.s.), nor the reduction of HbA1c levels during treatment (2.2 vs. 1.3% n.s.). Thus, diabetic retinopathy in this study was common among elderly Type 2 diabetic patients. The progression of retinopathy may in fact be associated with insulin treatment or improvement of metabolic control.     

Management of nevus spilus

BACKGROUND: Granulomatous gastritis is a rarely observed pathological diagnosis. This condition often mimics gastric adenocarcinoma clinically, resulting in gastric resection. However, granulomatous gastritis has long been viewed as a benign process not observed in association with adenocarcinoma of the stomach. This article describes a patient with granulomatous gastritis occurring in close proximity to an area of superficially invading gastric adenocarcinoma. METHODS: Acid-fast stains, fungal stains, standard cultures, tuberculosis cultures, and a VDRL serum test were all obtained. Both upper endoscopy and colonoscopy were performed. Chest radiographs were taken and pulmonary consultation was obtained. RESULTS: The gastric samples obtained from resection showed no evidence of foreign body reaction. The acid-fast stains, fungal stains, cultures, and VDRL were all negative. Endoscopic exams did not show granulomatous inflammation in any other part of the gastrointestinal tract. No pulmonary disease was evident on radiographic or pulmonary exam. CONCLUSION: Isolated granulomatous gastritis is a diagnosis of exclusion. The findings in this patient do not support a diagnosis of Crohn's disease, tuberculosis, sarcoidosis, syphilis, histoplasmosis, berylliosis, or foreign-body reaction. This is a unique case suggesting an association between isolated granulomatous gastritis and metaplastic mucosal changes.     

Three-dimensional power Doppler sonography of tumor vascularity

We used existing data on hepatitis C prevalence, injection-related hepatitis C transmission and needle use in prisons and new data on infectiousness, to estimate the size of study required to detect injection-related hepatitis C in UK prisons. A pilot study of 500 prisoners followed for 10 weeks would have a 65% chance of detecting a hepatitis C seroconversion, conservatively assuming one injection per prisoner per week, and a 3% transmission rate per injection, but uncertainty might persist as to whether transmission had occurred during a short incarceration or before it. If the actual transmission rate was 10%, as recently documented, then such a study would have more adequate statistical power. A definitive study of 3000 prisoners for 10 weeks would expect to detect about six seroconversions, even with conservative estimates of injection frequency and transmission rate. Adequate design and power of these studies is important because of the complacency that could result from false-negative findings. We suggest six risk-factor themes that studies should document.     

Painful nodular and plantar erythema in children

INTRODUCTION: According to our knowledge, only twenty-three similar cases have been reported in the literature. Possible hypotheses for localised painful red nodules on the feet in children include erythema nodosum, neutrophilic eccrine hidradenitis, traumatic plantar urticaria, vasculitis and cold panniculitis. CASE REPORT: We report a typical case of painful erythematous plantar nodules of the child. A 13-yr-old boy was first seen by a paediatrician for intermittent fever. The fever was associated with red, painful nodules on the soles. He was unable to walk. Routine blood chemistry parameters were within normal limits. Histopathologic examination of lesional skin revealed an image of septal and lobular panniculitis with vasculitis. Direct immunofluorescence study was not contributive. With proper antibiotic therapy, pain resolved within one week while fever and nodules cleared within two weeks. DISCUSSION: Briefly, this observation concerns a child disease occurring as painful erythematous plantar nodules. The lesions are spontaneously resolutive and the children are in good health. Our observation should constitute a supplementary group with the same classical symptoms of nodular plantar painful erythema of the child but moreover accompanied by a septal and lobular panniculitis with vasculitis at the histological examination. Further studies are necessary to verify these hypotheses.     

Measurement of the maturation parameter by using computer-assisted interactive image analysis may be helpful in the differential diagnosis between compound Spitz nevus and malignant melanoma

The so-called maturation parameter (MP) (that is, the ratio of the mean nuclear areas in the deep portion and in the superficial portion of a tumor) was measured and calculated using a computer-assisted interactive image analysis system in 29 compound Spitz nevi (SNs) and 37 primary invasive cutaneous malignant melanomas (MMs), of which 16 and 14 lesions, respectively, measured up to 1 mm in Breslow thickness (that is, thin). The MPs of the SNs and MMs were found to be 0.37-0.89 (mean +/- SD, 0.64 +/- 0.1) and 0.81-1.16 (mean +/- SD, 0.96 +/- 0.1), respectively (p < 0.001). The MPs of the subgroups of thin SNs and MMs were 0.56-0.87 (mean +/- SD, 0.67 +/- 0.1) and 0.86-1.10 (mean +/- SD, 0.98 +/- 0.1), respectively (p < 0.001). Most of the SNs and MMs had MP values of < 0.81 and > 0.89, respectively. This pattern of distribution prevailed in the subgroup of thin lesions. Thus, the previously shown difference in MPs between SN and MM for thicker lesions (> or = 1.0 mm) was demonstrated in this study in thin lesions (< or = 1.0 mm) as well. Although a relatively small area of overlap in MP values exists between compound SNs and MMs, including the thin ones, below this area the lower the MP value the more likely the diagnosis is SN, and vice versa.