Comparison of histological measures of skin photoaging.

BACKGROUND: Dermal elastosis is considered the histological 'gold standard' for evaluation of skin photoaging, but the relation of the level of dermal elastosis to other histological indicators of photoaging is not clear. OBJECTIVE: To investigate how various proposed histological measures of photoaging compare with the level of dermal elastosis. METHODS: Prospective, community-based study in Southeast Queensland, Australia, among 89 participants aged 40-82 years. Quantitative histology was used to evaluate 8 biomarkers of photoaged skin, and associations between grades of dermal elastosis and each of the other 7 biomarkers were analysed using ordinal logistic regression models with proportional odds assumption, using histological grades of elastosis as the outcome. RESULTS: Older age, male sex and high outdoor exposure levels were confirmed as predictors of high levels of dermal elastosis. After adjustment for age and sex, the only significant positive association with increasing elastosis grades was the proportion of p53-positive cells. Epidermal thickness, interdigitation index proportion of surface covered with melanin (% Fontana-Masson staining) and glycosaminoglycan content were not associated with elastosis in either crude or adjusted models. CONCLUSIONS: Among a range of suggested biomarkers of photoaged skin, only p53-positive cells appear to be strongly associated with the level of dermal elastosis.

Cutaneous manifestations of cytomegalovirus disease in renal transplant recipients: a case series.

Cytomegalovirus (CMV) is an important and well-described opportunistic virus in the immunocompromised host, with infection occurring mainly after the first month in the new renal transplant recipient. CMV can present as primary infection, reinfection, or reactivation of latent disease. It is capable of protean manifestations. Cutaneous manifestations are variable, rare, and diagnosis often delayed. We present 3 cases of cutaneous CMV disease in renal transplant recipients. Manifestations in our patients included ulceration of the tongue and perianal areas, facial petechiae, and nodular lesion involving the ear. This case series serves to highlight the importance of early skin biopsy in the diagnosis and management of cutaneous CMV disease.

A non-invasive measure of photoageing.

BACKGROUND: Photoageing develops in skin due to chronic sun exposure and a method of measuring photoageing would be useful in monitoring solar damage in populations, in studies of sun exposure as an aetiological agent, and in the evaluation of the effects of cosmetics and therapeutics. Methods of measuring photoageing include several invasive techniques as well as non-invasive techniques which are often difficult to use and have not been validated. The non-invasive measure of photoageing described here is a new method for grading silicone-rubber casts of the skin surface. This paper describes the development of the measure (named the sigma system) and compares its reliability and validity with the most widely-used similar measure (the Beagley and Gibson system). METHODS: Useable punch biopsies and silicone-rubber casts were obtained from 82 subjects. Two random subgroups of silicone casts were created and the first subgroup was used for the development of the sigma system, while the second subgroup was used to test validity. All casts were graded twice using the sigma system and twice using the Beagley and Gibson system by two observers. The gradings of the second subgroup of casts were compared with the degree of photoageing seen on histological examination of the biopsies. RESULTS: The intraclass correlation coefficient (ICC) for inter-observer reliability of the sigma system was 0.89, with 73 of the 82 casts graded at the same level of photoageing by the two observers. Intra-observer ICC were 0.84 and 0.87 for the two observers. The Goodman-Kruskal tau for agreement between the grade on the sigma system and histological degree of photoageing was 0.22. While these values are very similar to the reliability and validity estimates obtained using the Beagley and Gibson system, the sigma system is easier to learn and to use. CONCLUSIONS: The sigma system is a reliable and easy-to-use measure of photoageing which has many possible applications in monitoring and studying the effects of solar exposure.

Malignant melanoma of the gall bladder--does primary melanoma exist?

Although cases of both primary and metastatic malignant melanoma of the gall bladder have been reported, and the occurrence of metastasis to the gall bladder is well recognized, it is still far from clear as to whether a primary melanoma of the gall bladder is a definite entity in itself. Criteria which have been used to make the diagnosis of primary melanoma include the size and shape of the tumor, the presence of junctional activity within the tumor and the lack of another obvious primary site. We present a case of definite metastatic melanoma of the gall bladder however which demonstrates all these primary melanoma features. This must call into doubt the validity of these criteria as diagnostic aids, and ultimately the question remains--does primary melanoma of the gall bladder actually exist?

Two case reports of breast carcinoma associated with prolactinoma.

Two cases of breast carcinoma associated with prolactinoma are presented. Literature review reveals only five previous case reports of this association. Both of our cases occurred in women, aged 55 and 34. Both were typical of the reported cases in that they had long histories of amenorrhea before diagnosis of prolactinomas and breast carcinomas. One patient had a three and a half year history of atypical ductal hyperplasia and a prominent intraduct component in the invasive tumor. Both had axillary lymph node metastases. The significance of the association of breast carcinoma with prolactinoma is discussed. Whereas studies in animals have shown prolactin to be an initiator and promoter of breast carcinoma, studies in humans have been inconclusive. Some studies have shown raised levels of prolactin in patients with breast carcinoma and their daughters, while others have not. The paucity of case reports linking breast carcinoma and prolactinoma may indicate that the association is mere coincidence, but studies evaluating the relationship between breast carcinoma and all forms of hyperprolactinemia need to be conducted before a causal link is dismissed. Prolactin may act as a cofactor with, for example, estrogen or stress, to induce breast carcinoma.

PITX2 and non-canonical Wnt pathway interaction in metastatic prostate cancer.

The non-canonical Wnt pathway, a regulator of cellular motility and morphology, is increasingly implicated in cancer metastasis. In a quantitative PCR array analysis of 84 Wnt pathway associated genes, both non-canonical and canonical pathways were activated in primary and metastatic tumors relative to normal prostate. Expression of the Wnt target gene PITX2 in a prostate cancer (PCa) bone metastasis was strikingly elevated over normal prostate (over 2,000-fold) and primary prostate cancer (over 200-fold). The elevation of PITX2 protein was also evident on tissue microarrays, with strong PITX2 immunostaining in PCa skeletal and, to a lesser degree, soft tissue metastases. PITX2 is associated with cell migration during normal tissue morphogenesis. In our studies, overexpression of individual PITX2A/B/C isoforms stimulated PC-3 PCa cell motility, with the PITX2A isoform imparting a specific motility advantage in the presence of non-canonical Wnt5a stimulation. Furthermore, PITX2 specific shRNA inhibited PC-3 cell migration toward bone cell derived chemoattractant. These experimental results support a pivotal role of PITX2A and non-canonical Wnt signaling in enhancement of PCa cell motility, suggest PITX2 involvement in homing of PCa to the skeleton, and are consistent with a role for PITX2 in PCa metastasis to soft and bone tissues. Our findings, which significantly expand previous evidence that PITX2 is associated with risk of PCa biochemical recurrence, indicate that variation in PITX2 expression accompanies and may promote prostate tumor progression and metastasis.

Macroscopic vascular invasion in synovial sarcoma evident on MRI.

We present a case of recurrent synovial sarcoma in the soft tissues of the calf, where MR imaging not only confirmed the diagnosis of tumour recurrence, but also demonstrated direct venous invasion and tumour thrombus within the popliteal vein and its tributaries. Venous invasion has particular relevance to synovial sarcoma prognostication and should be actively sought on MR imaging. To our knowledge this is the first reported case in the English literature of histologically proven macroscopic popliteal vein invasion from a synovial sarcoma demonstrated on MR imaging.

Pathological variants of basal cell carcinoma.

Although the pathological features of basal cell carcinoma are well known, there is no generally agreed classification of the subtypes of this tumour. Certain histological subtypes are associated with indistinct clinical margins, inadequate primary excisions and frequent recurrences, and these must be recognized and reported by pathologists so that the most appropriate therapy is given. The current classification of subtypes of basal cell carcinoma is discussed and reference made to the rarer forms of this tumour.

Cutaneous light microscopic and ultrastructural changes in a fatal case of jellyfish envenomation.

A 5-year-old male suffered fatal envenomation from a jellyfish subsequently identified as Chironex fleckeri. Contact with the tentacles of the jellyfish had produced characteristic whiplash-like weals on the skin. At autopsy, skin from these areas was taken and later studied by light microscopy and electron microscopy. Both studies identified numerous nematocysts penetrating the epidermis and papillary dermis in the region of the sting.

Acro-angiodermatitis. A simulant of Kaposi's sarcoma.

Acro-angiodermatitis, usually related to venous insufficiency of the lower limbs, may simulate some of the features of Kaposi's sarcoma, both to the clinician and the dermatopathologist. With the increasing incidence of Kaposi's sarcoma related to the acquired immune deficiency syndrome (AIDS), there is a greater awareness of Kaposi's sarcoma than the benign simulant. Against this background, there is a danger that acro-angiodermatitis will be misdiagnosed as Kaposi's sarcoma.

The recognition of early stages of catagen.

Several criteria for recognition of follicles in catagen have been advanced, namely, loss of metachromasia in the hair papilla, subsidence of mitotic activity there, retraction of the lower portion of the follicle, and thickening and corrugation of the fibrous root sheath. The presence of scattered apoptotic cells in the outer root sheath is an additional marker of early catagen.

Apoptosis as the mechanism of the involution of hair follicles in catagen transformation.

Electron microscopy was performed on mouse skin to study the mechanism of the spontaneous involution of hair follicles during catagen. The reduction in follicles size appears to result from cell deletion by apoptosis, a distinct type of cell death with importance in tissue kinetics. These ultrastructural changes have been misinterpreted in the past as autophagic vacuole formation because of the prominent phagocytosis of the apoptotic fragments by adjacent, surviving cells of the hair follicle.

An experimental study evaluating the effect of minoxidil on the growth cycle of hair follicles.

The possibility that topically-applied minoxidil might affect the growth cycle of hair follicles was studied in inbred Herston white mice and HRA/Skh1 hairless mice. In the normal follicular cycle, the anagen or growth phase can be followed by autoradiographic demonstration of [3H]thymidine uptake in proliferating matrical cells, and the catagen or regression phase can be recognised, using light microscopy, by the presence of greatly increased death of matrical cells by apoptosis. Using these two markers, the effects of topically-applied minoxidil on follicular kinetics were studied, during neonatal hair growth and the spontaneous wave of hair loss that occurs 16 to 17 days after birth. Minoxidil at strengths of either 1% or 3%, applied daily to the dorsal skin of newborn mice from birth until 25 days of age, was found to have no recognisable effect. Despite this negative result, however, the study does show the potential for the use of apoptosis as a marker for catagen in research in dermatopathology.

Papillary apocrine fibroadenoma of the vulva.

An unusual papillary tumour of the vulva is described which exhibits apocrine features, as currently defined. The tumour has areas which resemble sclerosing adenosis of the breast and also exhibits mucinous and sebaceous differentiation. A review of the literature reveals a small number of similar lesions of the vulva. Many of these have been classified as lesions of ectopic breast tissue. In the absence of associated normal breast lobules it is impossible to differentiate these from lesions arising from apocrine sweat glands. This papillary apocrine fibroadenoma may represent a distinct cutaneous tumour occurring in this site.

Adult cutaneous Langerhans cell histiocytosis.

A 24-year-old male presented with a 4 year history of a crusted erythematous papular eruption of the scalp and external auditory meati and a 12 month history of painful perianal ulceration. A diagnosis of Langerhans cell histiocytosis was made and confirmed by skin histology. Extensive investigation revealed no systemic involvement. Rapid improvement occurred after intravenous 2-chlorodeoxyadenosine but relapse of perianal lesions occurred within 5 months. Local radiotherapy to the perianal region resulted in a complete remission sustained over 12 months.

Pustular vasculitis of the hands.

BACKGROUND: Several patients were observed with a peculiar cutaneous eruption limited to the dorsa of the hands and fingers. Clinically the lesions had some resemblance to those seen in Sweet's syndrome, but biopsy specimens showed severe leukocytoclastic vasculitis. OBJECTIVE: Our purpose was to characterize this eruption clinically and histologically and compare it with previously described diseases. METHODS: Six patients observed since 1977 are described. Skin biopsy specimens were obtained. RESULTS: In six women (age, 41 to 79 years) a symmetric eruption of papules and plaques limited to the dorsa of the radial sides of the hands and first three digits developed. The lesions resembled those of Sweet's syndrome and were associated with fever, sterile culture, blood neutrophil leukocytosis, nonresponse to antibiotic therapy, and rapid response to prednisone. Biopsy specimens showed a severe leukocytoclastic vasculitis. CONCLUSION: These patients appear to have a distinct entity that we have termed pustular vasculitis of the hands.

Granulomas associated with tetanus toxoid immunization.

Two patients developed localized nodular reactions at the site of prior tetanus toxoid injections. Histology of the lesions showed granuloma formation with central granular debris surrounded by a histiocytic mantle. Peripheral to this was a dense lymphoid infiltrate with eosinophils. Examination with energy dispersive x-ray microanalysis confirmed the presence of aluminium and phosphorus in the granular debris but not in the surrounding infiltrate.

Atypical fibroxanthoma: two unusual variants.

Two unusual fibroxanthomas were studied by light microscopy. The first case contained numerous osteoclast-like cells and resembled malignant giant cell tumour of soft tissues, a variant of malignant fibrous histiocytoma. Osteoclast-like giant cells were negative for lysozyme and alpha-1-antitrypsin. The second case contained areas of chondroid differentiation which resembled chondrosarcoma. Tumour cells within the cartilaginous areas were positive for S100 protein.