Biomedical subjects
Publications and source records attributed to S G Ronan.
Malignant melanoma is extremely rare in patients with albinism. To date, in the English language literature, there have been only sixteen documented cases of malignant melanoma in albino patients. These cases include thirteen cutaneous, one oral, one ocular, and one anal; only one of these was in a child. Here, we present the case of the youngest known albino patient to have cutaneous malignant melanoma.
A 20-month-old Kuwaiti girl had manifestations of lipoid proteinosis, a rare autosomal recessive disorder seen more commonly in Caucasians. This condition is diagnosed based on clinical, histopathologic, and ultrastructural criteria. Its biochemical and genetic aspects are still poorly understood.
PURPOSE: A study was performed to assess the usefulness of a radiolabeled monoclonal antibody (MoAb; technetium 99m NR-ML-05 Fab) as a detecting agent, as well as to evaluate its role in the overall decision-making process in the management of cutaneous malignant melanoma. PATIENTS AND METHODS: Twelve patients with histologically confirmed primary cutaneous melanoma and palpable regional nodes were injected with MoAb NR-ML-05 Fab, radiolabeled with 20 to 30 mCi of 99mTc. Whole-body anterior and posterior images were obtained. Left and right lateral views of the head and anterior and posterior views of the chest, abdomen, pelvis, and extremities were obtained, as were selected single-photon emission computed tomographic (SPECT) views of regional lymph nodes and areas of known or suspected lesions. RESULTS: In nine of 12 patients, clinical and/or MoAb evolution identified 30 discrete sites of suspected melanoma. The remaining three patients showed no positive sites, and there was no evidence of metastatic melanoma. All 30 sites were examined microscopically, and melanoma was confirmed histologically in 23. The remaining seven were negative. MoAb imaging detected 21 (true-positive) but failed to detect two (false-negative) lesions. Sensitivity was 91% (21 of 23); positive predictive value was 95% (21 to 22). CONCLUSIONS: MoAb imaging seems to provide an excellent way to obtain information with regard to the metastatic status of melanoma patients. Immunocytochemistry showed that MoAb (NR-ML-05) is as sensitive as the S-100 antibody and probably more sensitive than the commercially available antimelanoma antibody HMB-45.
To evaluate whether the increase in disease-free survival and survival previously reported for women with melanomas with estrogen receptors (ER) was a reflection of the histopathology of the primary melanoma, the interrelationship of histopathologic characteristics of 143 patients with such tumors was examined. The ER was assayed in the primary tumor from 44 patients and in 99 metastatic deposits from the other patients. Tumor thickness, level of invasion, prognostic index, mitoses/mm2, ulceration, vascular invasion, necrosis, histologic grade, preexisting nevus, and predominant malignant cell type were examined. There was no relationship between ER presence and any histopathologic characteristic examined, irrespective of the tumor source (primary or metastatic). Examination of histopathologic characteristics as a function of sex and receptor status showed a slight but insignificant predominance of more well-differentiated, thinner tumors in women whose lesions were positive for the ER. These results suggest that the increased disease-free survival in patients with ER-positive lesions is not attributable to the pathologic characteristics of the primary tumor examined during this study.
Initial results (Cancer Res., 48: 1708-1711, 1988) suggest that ovariectomy alters the proliferation of congenital exophytic melanoma in Sinclair swine. In order to provide a phenotypic basis for this effect, histopathological staging of 375 exophytic melanomas from 236 intact male and female Sinclair swine was compared with 114 lesions from 51 gonadectomized (6 weeks of age) and 90 lesions from castrated swine receiving s.c. silastic implants of estradiol during the first year of life. A rapid progression from actively proliferating tumor cells (Stages I-III) to regressive lesions (Stages IV-V) was virtually complete by 16 weeks of age in intact swine of both sexes. Bilateral ovariectomy reduced (P less than 0.02) tumor volume over time compared with intact animals. Replacement of estradiol in gilts increased tumor volume to that in intact animals. In contrast, neither bilateral orchidectomy nor estradiol replacement altered tumor volume in boars. Ovariectomy significantly reduced the tumor macrophage, keratinocyte, and fibroblast invasion that normally replaces tumor cells and expands tumor volume (Stages IV and V) with increasing age. Chronic exposure to estradiol reversed this process. Orchidectomy and estradiol replacement did not significantly affect histopathological stage in boars with increasing age. A significant number (20 of 41; 49%) of Stage III lesions (greater than 75% tumor cells) in swine of both sexes contained low but reproducibly measurable amounts of receptor for estrogen determined radiometrically and by enzyme-linked immunosorbent assay. These results suggest that reproductive steroids influence the natural history of these heritable lesions, and that the effect may be via alteration of host immune status.
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Clinical and pathologic variables were compared between "older" (greater than or equal to 70 years) and "younger" (30 to 39 years) patients with primary invasive cutaneous melanoma. Older patients had more nodular melanomas and acral lentiginous melanomas (58%); superficial spreading melanomas predominated in younger patients (74%). Mean tumor thickness was greater in the older patients (3.95 vs 2.02 mm). Invasive levels 2 and 3 occurred more often in younger patients (41.1% vs 13%); level 5 occurred more often in older patients (30.4% vs 5.3%). Microscopic ulceration occurred more often in older (46.4%) than in younger patients (19.4%). Older patients classified as clinical stage I at presentation or with primary lesions 1.50- to 3.00-mm thick had poorer survival. Younger women survived longer than younger men; this was not true of older patients. The elderly patients with cutaneous melanoma were more likely to have poor prognostic features and thus more likely to die from melanoma than the younger patients.
Fifteen women with genital malignant melanoma were studied. Their ages ranged from 19 to 66 years (mean 49.1 years); 12 were white, and three were black. The sites of involvement were the mons pubis (one patient), perineal body (one), labium majus (three), labium minus (three), and vagina (seven). Ten patients (66.6%) died of their disease, one is alive with disease, and four are alive without evidence of disease. For the living patients the duration of follow-up was 20 to 118 months (mean 63.6 months). Of those who died, survival ranged from 3 to 76 months (mean 25.1 months). The predominant type of malignancy was superficial spreading melanoma 50%. Nodular melanoma represented 22%, and the nodular polypoidal variant 14%. Melanoma of the squamous mucosa, also referred to as lentiginous melanoma, constituted 14%. By using Chung's method of determining levels of invasion, we found that no lesion was in situ (level I), two were level II (less than 1.0 mm thick), one was level III (between 1.0 and 2.0 mm) and the remaining 11 patients had lesions that were greater than 2.0 mm (levels IV and V). Because the subcutaneous fat is not consistently present in all sites of the female genitalia, all tumors thicker than 2.0 mm were included in level IV, and no level V tumors were classified in our study. Using Breslow's microstaging method, we found the thickness to range from 0.65 to 9.5 mm (mean 4.75 mm). When we correlated survival with level and thickness of tumor in nine patients who died, one tumor was level III and eight were level IV; thickness ranged from 1.65 to 9.0 mm (mean 5.64 mm).(ABSTRACT TRUNCATED AT 250 WORDS)
We report three cases of pigmented Bowen's disease that clinically and histologically had features of seborrheic keratoses. We speculate about the mechanism of pigmentation in these lesions and suggest that they arise from pigmented seborrheic keratoses.
A transferable computer program for the differential diagnosis of diseases of the skin, CLINDERM, has been produced for use by physicians on standard IBM and compatible personal microcomputers. This program lists the differential diagnosis and definitive diagnosis of any presented disease of the skin, except single tumors. The physician operator indicates the distribution and detailed description of lesions, which the interactive system integrates with a comprehensive knowledge base. The computer diagnosis in 129 cases was compared with independent interpretation of the same information by an academic dermatologist. Results were synonymous in 66.7% of all diseases and similar in an additional 4.7%. A common differential diagnosis was obtained in 24%, for a 95.3% rate of synonymous, similar, or common differential diagnoses. Diagnosis was different in 3.9% and description was inadequate for diagnosis in 0.8%. The variation in diagnosis showed that some descriptive terms are prejudicial of certain diagnoses; that diagnostic terms are not all completely standardized; that some diagnoses are variants of another disease; and that drug-induced eruptions simulate many other diseases. A skin disease can usually be diagnosed by specific description. Most lesions that are not diagnostic from inspection are nodular. A computer can be programmed to list diagnoses according to morphologic description.
We report a patient with disseminated strongyloidiasis who was being treated with steroids for cerebral edema caused by brain metastases from urinary bladder carcinoma. He had extensive purpura involving the abdomen, arms, and thighs. A skin biopsy specimen showed numerous larvae of Strongyloides stercoralis. Subsequently, rhabdoid larvae of S. stercoralis were isolated in the stool and the sputum. The patient died 2 days later despite thiabendazole therapy.
Pigmented tumors resembling cutaneous melanoma were first reported in Sinclair miniature swine in 1967. Since that time, carefully planned breeding has established that this is an inherited malignancy the natural history of which mimics human cutaneous melanoma in a number of ways. Because of these characteristics, miniature swine melanoma appears to be an effective model with which to investigate the mechanisms influencing initiation, growth, and progression of human melanoma. This investigation characterized histologically the cutaneous melanoma in miniature swine and compared the findings with human neoplasm. Primary cutaneous melanoma in swine has been reclassified and standardized according to the classifications currently in vogue in human melanoma. Our results suggest that the condition in miniature swine is histologically similar to that in humans. These observations will provide a basis for interpretation of the results derived in the biologic studies performed in this model.
We have analyzed the association between host hormonal status and growth rate of congenital exophytic melanomas of Sinclair swine. The growth of multiple exophytic lesions during the first year of life of intact males, orchiectomized males, intact females, and ovariectomized females was quantitated using a proliferative index which assigned a numerical value to fixed increments of gains or losses in tumor volume. The proliferative index from 6 wk (gonadectomy at 6 wk) to 52 wk of age of each treatment group was statistically increased from 0 (P less than 0.01) except that of gonadectomized females. The proliferative indices from lesions in gonadectomized females were significantly lower than those from intact males, intact females, and gonadectomized males. A total of 93 exophytic tumors from 63 swine were biopsied and histopathologically staged according to the degree of progression or regression and analyzed as a function of animal age. There were no Stage I and only two Stage II lesions at the time biopsies were taken. Twenty-six of 32 (81.2%) Stage III tumors were found in swine of both sexes less than 26 wk of age of which 71.8% were found less than 10 wk of age, while 20 of 29 (68.9%) were Stage IV, and only 3 of 32 (9%) were Stage V lesions present in this age group (P less than 0.001, chi 2). Only 20.7% of Stage IV tumors were present prior to 6 wk of age. Preliminary results suggest that castration of either sex also altered tumor histopathology. Our data suggest that a reduction in gonadal steroid secretion was associated with a decrease in exophytic tumor growth rate and regression in animals of both sexes during the first year of life in Sinclair swine. The effect in female swine was due to significant reduction in the proliferative index over the first 6 mo of age.
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A surgically created, totally autogenous venous valve has been devised that holds potential for the treatment of venous insufficiency. Valves were constructed from 2.7 cm long segments of canine external jugular veins. Through the use of intimal separation, folding, and suturing techniques, thin, pliable valves with an intimal lining were constructed and interposed in the canine superficial femoral vein. Fifteen valves were implanted in three groups of dogs. In group I (six dogs) the valves were immediately removed after implantation and subjected to various levels of hydrostatic pressure. In group 2 (six dogs) valves were removed after 1 week and examined for patency and competency. Group 3 animals (three dogs) were anticoagulated with subcutaneously administered heparin from implantation to removal at 7, 9, and 13 days. In group 1 valves were found to open at less than 3 cm of water and remain competent at 55 cm of water. Two of these valves subjected to 300 mm Hg pressure also remained competent. In the six group 2 dogs, two valves remained patent and competent, whereas four valves were patent but incompetent as a result of thrombus that prevented valve closure. In group 3 all valves were patent and competent at 7, 9, and 13 days after implantation. An autogenous venous valve that opens at physiologic pressures and remains competent at high pressures can be surgically created. The ability to remain competent at high pressures may give this valve an advantage over the repaired, transposed, or transplanted native venous valve in the treatment of chronic venous valvular insufficiency.
Among proponents of elective lymph node dissection (ELND) for clinical stage I melanoma, controversy exists as to whether there is an upper limit of tumor thickness beyond which ELND should not be considered. We reviewed 169 patients with clinical stage I and II melanoma that was greater than or equal to 3.0 mm thick and who were treated at the University of Illinois Hospital, Chicago. Of 139 patients with clinical stage I disease, 117 underwent ELND. Five- and ten-year survival rates were 55.7% and 48.9%, respectively. Multifactorial analysis demonstrated that anatomical location, level, pathologic stage, and ulceration were the best predictors of survival. Thickness did not emerge as a significant variable. Our findings do not support basing treatment decisions, eg, ELND in this group of patients, solely on the thickness of the primary tumor. We continue to recommend ELND in patients with either intermediate or thick melanomas.
A practical, transferable microcomputer system for differential diagnosis in dermatopathology, called TEGUMENT, has been developed for use by dermatologists on the standard IBM PC, Compaq, and other compatible personal microcomputers. In an interactive computer program a set of information is abstracted from the microscopic study of each specimen by a dermatologist, to compare with a structured knowledge base. The process leads through a relevant sequence of descriptive phrases until the findings can be allocated to a disease class. The microscopic description and diagnosis are then combined with clinical information by the computer and printed, optionally, as a pathology report. The identification and diagnosis of each case are preserved in permanent memory to enable future search and sorting. The results of independent validation are that a pathologist made the same diagnosis as the machine or a similar differential diagnosis in 91.8%, disagreed in 4.8%, and was unable to make a diagnosis from the description furnished by the machine in 3.4% of 147 actual cases. We conclude that a certain critical minimum of information is required for objective diagnosis; more information is needed for definitive than for differential diagnosis; a characteristic feature is necessary to distinguish between differential diagnoses; an objective description may admit of more than one diagnosis; ambiguity may be reduced by presenting for consideration all distinguishing features that characterize closely related diagnoses; and the personal microcomputer, programmed in this way, is of considerable assistance to the dermatologist in the histopathologic diagnosis of diseases and neoplasms of the skin.
The significance of partial regression in thin malignant melanomas (0.76 mm or less) of the skin was evaluated to determine if the regression was associated with the later development of metastases in patients who previously were considered to have a favorable prognosis. Of 575 patients with primary cutaneous melanoma treated and followed up by the Division of Surgical Oncology at the University of Illinois, Chicago, we found that 103 (18%) had tumors that measured less than 0.76 mm. Of these, 30 (29%) showed histologic evidence of partial regression. In six (20%) of the 30 patients, visceral metastases developed and the patients died. All six had more than 77% regression of their primary tumors. Of the remaining 24 patients, only one had regression greater than 77% and she is still alive three years after diagnosis. Most of these 24 (83%) patients had regression of less than 50% (mean, 29.9%). No metastasis occurred in the 73 patients who had thin melanomas without histologic evidence of regression. It is apparent from this study that patients with thin melanomas who show partial regression cannot be included in the "low-risk" group if the extent of regression is 75% to 80% or more.