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To assess the relationship between immune system and nevi, we studied two models of immunodeficiency caused by different mechanisms, i.e., virus and drug. Our rationale was that if an excess of nevi was found in these two epidemiologic models, it could be concluded that the excess was due to immunodeficiency itself rather than its cause. One hundred ten renal transplant recipients (RTR) were compared with age-, sex-, and phenotype-matched controls. Eighty four HIV-positive patients (HIV+) were compared with similarly matched controls. Nevi < 5 mm (N < 5) or > or = 5 mm (N > or = 5) were counted in three sites representative of regularly, intermittently, and never sun-exposed sites. The number of N < 5 was higher in RTR (p < 0.001) and in HIV+ (p < 0.001) than in respective controls. N > or = 5 were significantly higher only in RTR. These differences tended to be the same for all sites and persisted after adjustment for possible confounding factors. The incidence of atypical nevus was higher in RTR than in controls. Immunodeficiency seems to promote the occurrence of nevi. This supports the concept of immune surveillance of nevi and raises the question of whether sun-induced immune suppression plays a role in the development of nevi. As nevi are risk markers for melanoma, a higher incidence of melanoma could be expected in immunocompromised patients.

In 126 adult renal transplant recipients who had survived their transplantation for at least 8 years, we determined whether numbers of nevi and the presence of clinically atypical nevi were related to chronic sun exposure. On the basis of a skin examination, three groups were defined: patients with at least one clinically a typical nevus; patients with only clinically normal nevi: and patients without any nevi. The prevalence odds ratio of having any clinically atypical nevi as compared to having only clinically normal nevi was calculated in a logistic model, in relation to gender, skin type, age, sun exposure, and number of keratotic skin lesions present. Similarly, the prevalence odds ratio of having 30 or more nevi compared to fewer than 30 nevi was calculated. We found an inverse association between chronic sun exposure and age with numbers of nevi in adult renal transplant recipients. The presence of clinically atypical nevi was also inversely associated with chronic sun exposure, but this association disappeared after adjustment for age. We did not observe an association of nevi with the number of keratotic skin lesions, nor with humoral immune responses against human papillomavirus and the presence of certain HLA antigens, which are factors associated with nonmelanoma skin cancer in renal transplant recipients. Chronic sun exposure and age appeared to be strong determinants for decreased numbers of nevi in adult renal transplant recipients. Infection with human papillomaviruses does not appear to play an important role.

CD44 is a polymorphic family of cell membrane glycoproteins that mediate cell-matrix and cell-cell interactions involved in the mechanisms of tumor invasion and metastasis, and are subject to differential regulation during normal and malignant cell growth. We have investigated immunohistochemically the expression of CD44S and the variant isoforms CD44v3 and CD44v6 in paraffin-embedded tissue from 5 Spitz nevi, 3 compound melanocytic nevi, 2 blue nevi, 6 primary melanomas, 15 cutaneous metastases (three epidermotropic, nine dermal and three ulcerated) and 10 lymph node metastases of melanoma. Melanocytes were extensively positive for CD44S in primary melanomas and benign melanocytic proliferations. Among 15 cases of cutaneous metastases of melanoma, the three epidermotropic metastases, as well as one of the three ulcerated ones were positive for CD44S. CD44S expression was diminished or totally absent in six of the nine dermal metastases, in two of the ulcerated metastases and in seven of the ten lymph node metastases. CD44v3 and CD44v6 melanocytic expression was absent in all the lesions studied. According to our results, selective retention of CD44S expression by melanocytes in epidermotropic metastases of melanoma seems to indicate that preservation of CD44S may contribute to the intraepidermal spread of melanoma.

Aims: To draw attention to the possibility of simultaneous occurrence of pitfalls in breast pathology., Material and Methods: Presentation of a curious case with an association of granular cell tumour of the breast and neuro-naevic inclusions in axillary lymph nodes, first interpreted as metastatic mammary carcinoma., Discussion: Non malignant inclusions in axillary lymph nodes, rare but not unusual, may be erroneously interpreted as metastasis of carcinoma, establishing a wrong diagnosis of malignity in the breast. It is important to recognize this type of lesion and the possibility of their coexistence to correct the diagnosis. An approach to the histogenesis of this lesion is presented.

The associations of sun exposure, sunburn, skin color, and other constitutional characteristics with the density of nevi (2 mm or more in diameter) were assessed in a study of 410 secondary school children ages 14-15 years in Tasmania, Australia. Skin color was estimated by using a chromameter that measures across the visible light spectrum (400-700 nm). Skin color and lifetime history of sunburn were significant predictors of nevus density on the arms and legs of girls and boys and on the shoulders and backs of boys. The nevus density ratios between the highest and lowest exposure groups were 2.85 for the arms and legs of boys (P < 0.01), 2.19 for the arms and legs of girls (P < 0.01), and 1.72 (P = 0.03) for the shoulders and backs of boys. The increase in nevus density appeared to occur at lower levels of lifetime sunburn in children with light or medium skin than it did in children with darker skin. Darker-skinned children with a history of many sunburns ( > or = 11 lifetime sunburns) had a similar number of nevi compared with their lighter-skinned peers.

Background: These studies were designed to assess the influence of sun exposure on nevi in white people. To eliminate the confounding effect of age, sex, and phenotype, two parallel studies were conducted on people of the same age (17 to 24 years; median, 20 years old), sex (male), and phenotype: one in people with "red" phenotype (red or red-blond hair, white complexion on the inner part of the arm, and inability to tan) and one in people with "dark" phenotype (brown or black hair, dark complexion on the inner part of the arm, absence of freckles, and easy tanning without burning)., Results: In both groups, comparison of nevus counts on the inner and outer side of the upper extremities and comparison of mean density of nevi (number per square meter) in always-exposed and never-exposed skin show that the number of nevi is higher in sun-exposed areas. The density of large and atypical nevi was maximal on intermittently sun-exposed skin while the density of small nevi was maximal on always-exposed skin. The number of large nevi on intermittently exposed skin correlated with cumulative intensive exposure during beach recreation in the red phenotype group. The number of large nevi was significantly higher in red phenotypes who repeatedly experienced severe sunburns in their first 20 years of life., Conclusions: The number of nevi at the end of the second decade is influenced by cumulative sun exposure from birth. "Traumatizing" sun exposure, which is more frequent in the red phenotype than in the dark phenotype, has an influence on the number of large nevi and is therefore likely to make small nevi grow.

There is evidence from previous studies of small numbers of children who received cytotoxic therapy for cancer, that they may develop increased numbers of melanocytic naevi (moles), the strongest known risk factors for melanoma. Our aim was to investigate a large number of survivors of childhood cancer in order to test the hypothesis that they have more melanocytic naevi than matched controls. Total-body naevus counts were obtained from 263 oncology patients ascertained in paediatric oncology departments in Queensland, Australia, and from 263 hospital controls matched for age and sex. Additional information was gathered from children's parents about concurrent factors influencing naevus development such as type of complexion and history of sun exposure. Matched analyses, both crude and adjusted for possible confounding factors, revealed no significant difference in overall density of naevi among oncology patients and control subjects, according to diagnosis or to duration or type of chemotherapy. However significantly more oncology patients had atypical naevi (P < 0.05) and acral naevi (P < 0.0001) than controls. One patient developed a malignant melanoma 13 years after chemotherapy and radiotherapy for rhabdomyosarcoma. These findings support an association between treatment for childhood cancer and acral naevi and suggest that atypical naevi may also be associated with chemotherapy in childhood.

Intermediate lesions of melanocytic tumor progression are potential precursors, simulants, and risk markers of melanoma. The clinical, public health, and biologic significance of intermediate lesions warrants their continued recognition and study, although improved schemata for their clinical and histological coding are needed. Blurred boundaries are inherently problematic to the categorization of lesions occurring along a stepwise pathway of increasing clinical and histological atypia. Nevertheless, the concepts of melanocytic dysplasia and of radial growth phase (in situ and microinvasive) melanoma are important to the classification of intermediate lesions of melanocytic tumor progression. Conceptually, these lesions are clearly separable from early and late lesions and from one another, and there is evidence that criteria distinguishing them can be reproducibly applied. Analysis of these intermediate lesions suggests that they represent responses to events (perhaps mutational) induced by ultraviolet light in constitutionally hypersensitive individuals, supporting epidemiological data that implicate sunlight as an etiologic agent for most melanomas. The continuing rigorous application of the methodologies of epidemiology and basic science to the study of these lesional steps will likely lead to the recognition of biologic markers to better distinguish benign from malignant melanocytic lesions.

Background: Conflicting evidence exists on the relation between sun exposure and the number of common acquired nevi. The increase in the number of common acquired nevi until early adulthood and their greater concentration on sun-exposed areas suggested that the growth of common acquired nevi is promoted by UV radiation. Nevertheless, it was noticed that although solar exposure accumulates with age, the number of common acquired nevi decreases after the third decade., Objective: Our purpose was to examine the relation between the prevalence of common acquired nevi and accumulative sun exposure., Methods: The number of common acquired nevi on 128 patients with multiple solar keratoses (SK) was compared with their number on 82 control subjects. The existence of SK served as a biologic marker for long-term solar effects., Results: On patients with SK we counted 1285 nevi (mean 10.0 nevi per person) and on control subjects, 1521 nevi (mean 18.5 nevi) (p = 0.0046; Kruskal-Wallis test). The finding that persons exhibiting signs of accumulating sun effects have fewer nevi was maintained irrespective to differences of gender, occupation, and complexion., Conclusion: Our data suggest that accumulating solar effects may contribute to the natural maturation and elimination of common acquired nevi in late adulthood.

We examined the role of UVR (UV radiation) (UVA, 320-400 nm; UVB, 290-320 nm; and the combination of UVA and UVB) as a promoter in the induction of cutaneous melanoma. One hundred and seventy hairless mice (Skh-hr2), 6-8 weeks old, were treated in 8 groups: group I, DMBA [7,12-dimethylbenz(a)anthracene] plus UVA; group II, DMBA plus UVA plus UVB; group III, DMBA plus UVB; group IV, DMBA; group V, UVA; group VI, UVA plus UVB; group VII, UVB; group VIII, control. DMBA (0.5% solution) was applied once to promote the formation of dermal melanocytic nevus-like lesions while UVR treatments were conducted 3 times/week for 30 weeks. The mice were examined periodically for the development of multiple pigmented lesions, papillomas, squamous cell carcinomas, melanomas, and lymphomas. Treatment with DMBA plus UVA, DMBA plus UVB, and DMBA plus UVA plus UVB stimulated the development of multiple pigmented nevus-like lesions (85-100%) in mice of groups I, II, III, and IV. Upon necroscopy, 27-33% of animals in groups I, II, and III receiving UVR treatments developed clinically and histologically characterized melanomas. Treatment with DMBA alone did not produce melanomas. DMBA-treated animals in groups I, II, and III which received UVR treatments also developed lymphomas (21-50%). Animals treated with DMBA alone or those that received UVB or the combination of UVB plus UVA (without DMBA) developed only papillomas and squamous cell carcinomas (25-47%). Skin tumors were analyzed for the presence of point mutations in the ras gene. Polymerase chain reaction amplification of DNA and selective oligonucleotide hybridization revealed mutations in the 61st codon of the N-ras gene in the precursor nevus-like lesions and melanoma samples studied. This study suggests that UVR (both UVA and UVB) plays a role as a promoter in the stimulation of melanoma and lymphoma development in hairless mice.

We have suggested that pigmented macules on the palms and/or soles occur in response to various systemic diseases. In the present paper, we evaluated the influences of clinical severity and duration of illness in Japanese subjects. In males, cases who suffered from cerebral vascular accident (CVA) for long periods and/or severely tended to have numerous pigmented macules. In females, cases with CVA did not show any similar tendency. As the result of our prior and present studies, we conclude that underlying systemic disease itself can play a pivotal role in the development of pigmented macules on the palms and/or soles of Japanese subjects. We emphasize that such a pigmented macular eruption with characteristic clinical features is an important sign of internal disorders, including malignancy.

A possible association between oral contraception and the development of cutaneous melanoma has been raised largely because of the hyperpigmentation of pregnancy and the effect pregnancy may have on the outcome of established disease. Present evidence suggests there is no causal link between oral contraceptive (OC) use and melanoma (or with benign melanocytic nevi), nor has a specific subgroup of women or subtype of melanoma been consistently implicated as being at increased risk of this disease due to use of OCs.

To investigate the UV effect on epidermal melanocytes, 21 volunteers and 11 patients with dysplastic nevus syndrome (DNS) received UVB irradiation three times weekly during 17 days. Skin biopsies were taken before and three weeks after the last irradiation (on day 37) from exposed and covered buttock skin. The epidermal melanocyte population density was estimated in dopa-stained split skin preparations. The biopsies taken on day 37 revealed that repeated UVB irradiation induces an increase in the number of melanocytes not only in exposed but also in covered skin. This increased mitotic activity might be a link between sun exposure and melanoma development in covered skin. The size of the proliferative response was inversely correlated to the basal melanocyte number. The larger population increase in skin with few melanocytes might amplify the propagation of DNA damage and increase the likelihood of tumor development. The pigment metabolite 5-S-cysteinyldopa (5-S-CD) was measured in urine before the irradiation and twice weekly until day 38. No correlation was found between the basal 5-S-CD excretion and the size or activity of the melanocyte organ, suggesting that the basal 5-S-CD excretion is mainly of non-melanocytic origin. Despite numerous nevi, DNS-patients did not differ from controls in their 5-S-CD excretion. The normal upper range for the tumor maker 5-S-CD is therefore valid in these melanoma-prone subjects. During the irradiation, subjects with a low tanning ability developed a more pronounced erythema and excreted more 5-S-CD than those with a good tanning ability. This suggests that the UVB-induced 5-S-CD excretion is rather due to melanocyte damage than to an increased melanin synthesis. To investigate the influence of sun exposure on the development of nevi and melanoma (CMM), the distribution over the body surface of CMM, common nevi (CN) greater than or equal to 2 mm and dysplastic nevi (DN) was registered in 121 melanoma patients and 310 controls. Four times as many nevi were found in a sun-exposed area than in a comparable sun-protected area, demonstrating that sun exposure plays an important role in nevus development. Subjects with DNA had a larger difference in nevus counts between the two areas than subjects without DN, indicating a different UV-dose and/or a higher sensitivity to the "nevogenic" effect of UV-light than subjects without DN.(ABSTRACT TRUNCATED AT 400 WORDS)

Vascular nevi occur in up to 70% of infants. The term includes hemangiomas, of which the majority involute, and vascular malformations, such as port wine stains which tend to persist. The appearance, and in some cases rapid growth of the lesion, may be alarming to the parents and may cause great distress to the patient. In rare cases systemic involvement and associated abnormalities may be life threatening or permanently disabling. Correct diagnosis of the type of lesion is vital to know the prognosis of the lesion, the likelihood of complications and whether investigations and treatment are indicated.

An animal experiment is presented in which pigmented hairless mice were exposed once per fortnight to high doses of ultraviolet B (UVB) to study tumorigenesis. The aim of the study was to confirm a causal relationship between cutaneous melanoma and UV radiation, and to find an animal model to study it. The experiment was based on the hypothesis that the risk of developing a melanoma is increased by a history of severe sunburns. Pigmented hairless mice, Skh-hr2, were exposed once every fortnight to high doses of UVB radiation from fluorescent sunlamps, Westinghouse FS40 T12. Heavy actinic damage was observed for several days after each exposure. Seventeen of the 24 animals eventually developed tumors. Histopathologically, 80% of the tumors were squamous cell carcinomas. Depositions of melanophages were observed, but no melanomas. In this mouse experiment no causal relationship between cutaneous melanomas and UV radiation could be established.

A child with connective tissue naevi is described. She was exposed in utero to maternal varicella and has evidence of congenital varicella infection. It is proposed that her cutaneous lesions are also a manifestation of this infection.

Meningocoele manqué is a congenital anomaly relating to the spinal cord, cauda equina and the filum terminale commonly found on exploration of the spinal cord in cases of spina bifida occulta. The anomalies consist of fibrous bands, aberrant nerve roots and adhesions within the theca which may tether or press on the neural structures so interfering with nerve conduction and causing increasing neurological deficit. Treatment is to free the neural structures from these bands and adhesions surgically. An account is given of 45 cases with a discussion of their similarity to cases of meningocoele, thus justifying the naming of a previously undescribed clinical entity. Meningocoele manqué demonstrates the relation of spina bifida occulta to spina bifida cystica as having a similar origin differing only in degree of severity. All the cases discussed are drawn from a personal series of 200 cases of spina bifida occulta which have had surgical exploration of the spinal cord.

Aggregates of cells resembling those of cutaneous nevi have been found in the capsules of lymph nodes. Although seemingly rare, this extraordinary lesion could conceivably occur often enough to be more than a pathological curiosity, and should be differentiated from metastatic tumor. Slides from every axillary lymph node dissection for female mammary carcinoma in the years 1964 and 1974 at Memorial Hospital were reviewed, as were slides from 100 consecutive lymph node dissections performed during 1974 in patients with malignant melanoma. Nevus cell aggregates (NCA) were associated with three of 17,504 lymph nodes (0.017%) obtained from 909 mastectomies, or 0.33% of the cases. Among the 100 lymph node dissections for malignant melanoma, NCA were found associated with three of the 2,607 lymph nodes examined (0.12%), or 3.0% of the cases studied. Since NCA occur in association with lymph nodes more often than previously thought, the possibility that they may be a potential source of malignant melanoma in patients without a demonstrable cutaneous or mucosal primary is discussed.

Examination of patients with nevus flammeus or nevus anemicus showed disturbed sensibility in the area of the nevus in the majority of cases. Histologically and with special technique of histochemistry and fluorescencemicroscopy there was no evidence for neurogenic lesions. However, signs of vegetative dysfunction were present: hyperhidrosis and absent reactivity of vasculature in the nevus area to vasoconstrictive and vasodilatatory stimuli. Based on these findings a disturbed regulation of vascular intramural adrenergic receptors seemed possible and really could be demonstrated by means of autoradiography. In both types of nevi only one of the adrenergic receptors could be marked with specific antagonists. Therefore the persistent vascular dilatation and constriction can be accounted for by the absence of one of these receptors. This abnormal distribution of receptors could be due to a developmental defect influenced by the "nerve growth factor".

A rare case of Sturge-Weber syndrome without facial nevus and epileptic seizures is reported. The other cases of incomplete form of the disease reported in the literature showed occipital calcification and epileptic seizures without facial nevus, while in the present case also the convulsions were absent. The possible pathogenic mechanism is discussed. The CT findings of these incomplete forms include unilateral or often bilateral occipital calcifications with no evidence of contrast enhancement. The Authors conclude that the radiologic finding of bilateral gyriform calcifications in the occipital region must suggest the diagnosis of Sturge-Weber disease even in the absence of facial nevus and epileptic seizures.

In 104 consecutive Caucasian patients who had histologically proved dysplastic nevi, the number and diameter of nevocytic nevi were determined in two equally sized contiguous rectangles in the lumbosacral region. The cephalad (superior) rectangle was in a relatively sun-exposed site, whereas the caudad (inferior) rectangle was in a relatively sun-protected site. Many of the nevocytic nevi identified in these rectangles had the clinical features of dysplastic nevi. Significantly, more nevi were found in the cephalad rectangle compared with the caudad rectangle. Men greater than or equal to 40 years of age had significantly larger nevi in the cephalad rectangle compared with the caudad rectangle. These data are consistent with the hypothesis that sunlight promotes development of more and larger nevocytic nevi in individuals afflicted with dysplastic nevus syndrome.

A nevus is a cutaneous lesion characterized histologically by clustering and disorganization of a variety of cell types in the skin including the epidermis, appendages, melanocytes, and their precursor cells. Commonly, a nevus is congenital but it may be acquired. Owing to the prevalence and variations of melanocytic nevi and their association with malignancy, this article discusses the development, classification, histology, and clinical characteristics of nevi with an emphasis on the relationship to malignancy. Recommendations are provided for treatment of these benign lesions.

Investigations by use of the formaldehyde-induced fluorescence (FIF) method in benign and malignant pigment tumors of the skin are the main basis of the present monograph concerning the theory of the dualistic histogenesis of melanoma according to Mishima. Furthermore, the value of the FIF method in both classification and diagnosis of pigment-producing tumor cells after certain forms of therapy is emphasized. Experimental studies with nevus cell nevi have gained important findings on the histogenesis of nevus cells. These results indicate that nevus cells are possibly derivatives of normal melanocytes, for nevus cells in junctional nests still show a dendritic pattern like melanocytes. Based on photocatamnestic studies it can be concluded that the initial growth of melanoma may be very protracted. There are many indications that pigment spots which had sometimes existed for decades and were mistaken for nevi were malignant from the very beginning and had developed from the melanocytes of the epidermis. The development of melanomas on nevus cell nevi seems to be an exception. However, in these cases, too, malignant transformation occurs in the melanocytes of the epidermis overlying the nevus rather than in the nevus cells. This is confirmed by the findings obtained by the FIF method; under certain conditions dendritic cells may be demonstrated in all types of melanoma, which gives support to the unitary melanocytogenic origin of the tumor. However, typical dendritic tumor cells in great numbers are only visible in lentigo maligna. In the other tumors (e.g., SSM or NM), the shape of the tumor cells and the growth of the melanoma are probably dependent on the varying degree of cell dedifferentiation, the ability or unability for horizontal spreading growth as well as on terrain factors. However, there is every reason to believe that melanoma cells originate from melanocytes of the skin (or mucous membranes).

An 8-year-old child with a ring chromosome 7 is presented, the first female and the fourth such individual to be described. The associated anomalies were rather benign: she presented with short stature, minor skeletal alterations, and normal intelligence. The only truly striking feature was the presence of multiple large, pigmented naevi, suggestive of a hamartomatous origin, but unlike those typical of any particular syndrome. Though other ring 7 patients have had naevus flammeus, and one had café-au-lait spots, our proband is the first with an anomaly of chromosome 7 to have such extensive lesions. These four cases of ring 7, which show great phenotypic variation, are reviewed, and the clinical presentation of the proband is also compared with that of patients suffering from terminal, interstitial and translocation-derived 7p and 7q deletions. The formation and behavior of ring chromosomes are discussed, as are the cytogenetic factors which may influence their phenotypic expression.

Port wine stains have been shown to be lesions formed by the progressive dilatation of vessels within the superficial cutaneous vascular plexus. Previous investigators have been unable to define abnormalities of vessel structure or perivascular stromal tissues. We, however, have demonstrated morphologically that port wine stains are lacking proper innervation, and have shown them to behave differently than normal skin, physiologically. Dermal vessels are under the control of sympathetic nerves which course through the dermis and cause vasoconstriction without a parasympathetic system for counterregulation. We, therefore, propose that continued blood flow in the absence of tonic modulation is the basis for the vascular ectasia that characterizes the port wine stain.

The aetiopathogenetic and evolutive problem of primary oral melanoma is examined with particular regard for melanosis and its relationship with oral naevi. These lesions are classified differently by Authors with different opinions regarding their ability to turn malignant. In this regard, the latest and most reliable hypotheses on the subject are put forward.

Eight choroidal melanomata and 3 suspected naevi were observed in 11 diabetics. One xenon-arc treated tumor was followed up for 7 years; two tumors had Strontium90 radioactive plaque brachytherapy and their follow up was 3 years and 6 years.

There exists a large body of evidence that the occurrence of nevocytic nevi is closely related to skin complexion. Nevi are more frequent in Caucasians with a light skin than in those with a dark phenotype. In Orientals and Negroids nevocytic nevi are uncommon. Within a black population subjects with a relatively light complexion have greater total counts than those with a very dark skin. It is concluded that literature data dealing with mole proneness in relation to skin complexion strongly point to an association of high nevus counts with light complexion. This applies to differences between racial groups as well as to differences between complexion phenotypes within a given racial group.

205 recipients of renal allotransplants were evaluated either by clinical examination (n = 91) or by study of records (n = 114). More than 75% of the patients studied had dermatologic problems in the late post transplant phase, 25% having 2 or more such conditions. Steroid related complications were most often observed, i.e. cushingoid in 42%, acne in 26%, hirsutism in 19%, purpura in 12%, and rubeosis in 12%. Infections included warts (29%), herpes simplex (13%), herpes zoster (7%), and candidiasis (29%). 9 patients (4.4%) had skin carcinomas which were diagnosed on average 6.2 years after transplantation. The frequency of skin lesions during immunosuppressive therapy after renal allotransplantation requires regular skin inspections and information to patients on the potential risks.

A patient was seen with several congenital anomalies and bilateral branchial cleft sinuses that clinically resembled inflammatory linear verrucous epidermal nevi. This unusual condition most likely represented a cutaneous reaction to residual branchial remnants and prior surgical therapy.