The stromal reaction in basal cell carcinomas. A prerequisite for tumour progression and treatment strategy.

Specimens of basal cell carcinomas collected from 28 patients were classified into three groups: superficial, nodular, and infiltrative, according to their microarchitecture. The specimens were then subjected to histological characterization by means of a biotinylated hyaluronan-binding probe (HABP). By using Ki-67 and PCNA the proliferative activity of the BCC tumours was evaluated with immunohistological techniques. In superficial BCC the tumour islands displayed moderate hyaluronan (HA) staining. Feeble proliferation, denoted by modest mitotic activity and weak Ki-67 and PCNA immunoreactivity, occurred within the tumour islands. The surrounding connective tissue resembled normal skin, and no differentiated tumour stroma was observed. In nodular BCC, the HA staining of the tumour strands was weak to moderate, denoting increased proliferative activity. The differentiated surrounding tumour stroma stained strongly for HA. Tumour islands of infiltrative BCC stained weakly to moderately to HA and evidenced intense proliferation. The intensely HA-stained tumour stroma ended abruptly and the adjacent areas were almost devoid of HA. This study showed that the proliferative activity of BCC cells is associated with increased expression of HA in the tumour stroma. Modification of tumour-associated connective tissue indicates a close relationship between the tumour cells and the adjacent matrix. In particular, in infiltrative BCC, such alterations include degeneration and possible modification and remodelling of the surrounding extracellular matrix. These processes involving areas of probable importance for tumour progression, should be considered when deciding the extent of intended surgical resection.

Is vulvar vestibulitis an inflammatory condition? A comparison of histological findings in affected and healthy women.

Vulvar vestibulitis, as defined by Friedrich, is considered to be inflammatory, despite the fact that the normal histology of this specific area has previously not been characterized. The aim of the present study was to compare the normal histology of the vulvar vestibulum with findings in localized vulvar vestibulitis. Biopsies were taken at the area of the vestibulitis, i.e. at the openings of the Bartholin's duct. Eleven control specimens were examined histologically and compared to 24 specimens obtained from 20 patients. All samples were also tested for human papillomavirus, and they were all negative. In control specimens, as well as in specimens from patients, subepithelial inflammatory cells, sometimes aggregated into lymph follicles and/or small groups of lymphocytes were found. The conclusion is reached that the occurrence of inflammatory cells in vestibular tissue is a normal finding and cannot serve as a histological indicator of vulvar vestibulitis.

The gene for diffuse palmoplantar keratoderma of the type found in northern Sweden is localized to chromosome 12q11-q13.

Hereditary palmoplantar keratoderma is characterized by hyperkeratosis of the skin of palms and soles. An autosomal dominant form of diffuse non-epidermolytic palmoplantar keratoderma, frequently complicated by fungal infections, is encountered in northern Sweden with a prevalence of 0.3-0.55%. We have examined two families with this type of palmoplantar keratoderma and localized the causative genetic defect to a 14 cM interval on chromosome 12q11-q13, a region known to contain the keratin type II gene cluster as well as the retinoic acid receptor gamma gene. The palmoplantar keratoderma variant investigated in this study is thus genetically different from epidermolytic palmoplantar keratoderma, which recently has been shown to result from mutations in the gene for the type I keratin 9.

The dominant form of hereditary palmoplantar keratoderma in the northernmost county of Sweden (Norrbotten).

The frequency of autosomal dominant inherited palmoplantar keratoderma (HPPK) in the northernmost county of Sweden (Norrbotten) is 0.55%. Histopathological examination of 91 biopsies from patients with the dominant form of HPPK revealed no case of epidermolytic PPK. This finding is in contrast to the results of a re-examination of descendants of the original family published by Thost which showed the characteristic features of epidermolytic PPK, and re-evaluation of biopsies from other families has shown that it is the most frequent type. The existence of PPK type Unna-Thost in relation to epidermolytic PPK and to HPPK of the northernmost county of Sweden will be discussed. At the same time a revision of designation of this type is proposed. A dermo-epidermal mononuclear cell infiltrate belongs to the classical description of PPK Unna-Thost. It was shown that this cell infiltrate occurs significantly more often in patients with HPPK and dermatophytosis. Relapsing vesicular eruptions along the hyperkeratotic border are a clinical sign of the severity of dermatophyte infections. Such spongiotic vesicles together with a mononuclear cell infiltrate should be considered as eczematous reaction to dermatophytosis.

Conjunctival involvement in familial amyloidotic polyneuropathy.

The present study is an evaluation of the possibility of using conjunctival biopsies for establishing the diagnosis of systemic amyloidosis of neuropathic type. Amyloid deposits were demonstrated in conjunctival biopsies from 15 of 16 patients with polyneuropathy and from 1 of 4 patients with vitreous opacities as the only symptom. Thus the sensitivity of conjunctival biopsies for the diagnosis of systemic amyloidosis of this type is similar to that of biopsies from other tissues. It is concluded that a conjunctival biopsy is a useful diagnostic tool since the technique is simple and there is little discomfort for the patient.

Single cell DNA cytophotometry in clinical stage I malignant melanoma. Relationship to prognosis.

Histological sections of 50 clinical stage I cutaneous melanomas were analyzed by single cell DNA cytophotometry. Forty-two percent of the melanomas had diploid modal values. Ploidy was not significantly related to the level of invasion, melanoma thickness or prognosis. These results are contradictory to published data from flow cytophotometry which, however, differ inter alia concerning patient materials and follow-up times. Mean nuclear area was in our study significantly correlated to the prognosis.

Erythema elevatum diutinum--a case successfully treated with colchicine.

A case of erythema elevatum diutinum, unresponsive to dapsone but successfully treated with colchicine, is described.

Flow DNA-cytometric findings of paraffin-embedded primary cutaneous melanomas related to prognosis.

In a retrospective study flow cytometry was performed in 82 paraffin-embedded clinical stage I cutaneous melanomas. A significant correlation of ploidy to melanoma thickness was found. Using a log rank test ploidy was found significant for prognosis. However, using the Cox's proportional hazard test the influence of ploidy vanished and melanoma thickness or Clark level of invasion together with sex and location were the factors most important for prognosis.

Karyometric findings and prognosis of stage I cutaneous malignant melanomas.

A material consisting of 82 stage I cutaneous melanomas was analysed clinically, histopathologically and karyometrically. High age, deep Clark level of invasion and thick melanomas were associated with a negative prognosis. There was a good correlation between the nuclear area and the melanoma thickness. By applying Cox's proportional hazard method to clinical, histopathological and karyometric data, it was demonstrated that karyometry provided both prognostic and biological information. Both a large variation (percentile 90-percentile 50) in nuclear area and a large standard deviation of form factor was related to a negative prognosis (p less than 0.0003 and p less than 0.04 respectively).

Proteolytic degradation of desmosomes in plantar stratum corneum leads to cell dissociation in vitro.

Pieces of plantar stratum corneum were incubated with trypsin. This resulted in cell dissociation. The only observable ultrastructural change caused by trypsin was a degradation of desmosomal plates between dissociating cells. This suggests that desmosomes are of primary importance in plantar stratum corneum cell adhesion.

Congenital ichthyosis with alopecia, eclabion, ectropion and mental retardation--a new genetic syndrome.

A syndrome with severe generalized congenital ichthyosis, alopecia, eclabion, ectropion and mental retardation without neurological symptoms or macular changes in the eyes was seen in two sibs and in two aunts and uncles in an inbred North-Swedish family. The clinical picture of the patients in the present family strongly deviated from that seen in the Sjögren-Larsson syndrome found in the same area. This could be a new syndrome with autosomal recessive inheritance.

DNA-cytophotometry of benign compound and intradermal naevi, Spitz epithelioid naevi and malignant melanomas.

Single cell DNA cytophotometry was used to characterize seven compound, ten intradermal and six Spitz naevi as well as 23 primary cutaneous malignant melanomas. Compound and intradermal naevi were characterized by a smaller nuclear area than both Spitz naevi and malignant melanomas. Tumour ploidy could not be used as a single criterion of malignancy since both diploid and hyperdiploid melanomas were encountered. The very low mean optical density of Spitz naevi served to distinguish these lesions from malignant melanomas.

Caryometry of benign compound acquired naevi, Spitz epitheloid naevi and malignant melanomas.

In order to get basic caryometric data later to be used in a prognostic study for malignant melanomas, caryometry of 7 compound acquired naevi, 8 Spitz epitheloid naevi and 83 cutaneous malignant melanomas was done and showed mean nuclear profile areas 32.9 microns 2, 73.6 microns 2 and 64.7 microns 2, respectively. Only minimal overlapping existed between the compound acquired naevi and the two other tumour types. Similar differences existed concerning mean maximal profile diameter, proportion of large nuclei and width of nuclear histograms. Mean form factor was lower for the malignant melanomas than for the naevi. The nuclei of the superficial layer of the compound naevi and the Spitz naevi were larger than those of the deep layer. A similar consistent pattern did not exist for the malignant melanomas.

Nonfamilial polycystic kidneys without enlargement.

7 middle-aged males with bilateral, polycystic, nonfamilial kidneys without enlargement are described. The histological examination revealed multiple cysts of varying sizes and changes such as in interstitial nephritis. 6 of the patients had hematuria and/or calculi in the urinary tract. The etiology of the cysts is not clear. The picture does not conform to that of congenital cystic kidney. The cysts might possibly be a final phenomenon in contracted kidneys, so-called acquired cystic disease, but it should be noted that in 4 of the 7 cases the cystic degeneration was demonstrated log before the uremia appeared. Another possibility is that the cystic transformation described here might be attributed to a specific type of interstitial nephritis.

Highly refractile myocardial echoes in familial amyloidosis with polyneuropathy. A correlative echocardiographic and histopathological study.

Two-dimensional echocardiography in systemic amyloidosis has in most cases shown highly refractile myocardial echoes. The morphological basis for this finding has so far been little examined. In the present study, echocardiographic examinations were performed in vitro on autopsied hearts from ten patients with familial amyloidosis with polyneuropathy (FAP). An ultrasonically visible needle was used to localize the abnormal echoes, and samples were taken for histological analysis of the region of the echocardiographic abnormality. Our results indicate that the highly refractile myocardial echoes in FAP are due to nodules composed of collagen and amyloid.

Karyometric investigations on urinary bladder carcinoma, correlated to histopathological grading.

The aim of this study is to provide karyometric data which may be of value in the grading of urinary bladder tumours. For this purpose 27 biopsies were studied: four from normal bladder mucosae, eleven from grade I tumours, six from grade II tumours and another six from grade III tumours, according to a I-IV scale. After standardized fixation and plastic embedding, semithin sections were used for light microscopic stereology. Mean profile areas and mean volume densities of the nuclei tended to be higher in the more malignant cases. The nuclear volume densities were significantly higher in grade II than in grade I. The most important finding relates to the large nuclear profiles (greater than 90 microns 2), which were found almost exclusively in grade III tumours. Simple measurements of nuclear size can thus provide objective data to aid in the diagnostic procedure.

Sjögren-Larsson syndrome: a dermato-histopathological study.

Thirty-six Swedish patients with the recessively inherited Sjögren-Larsson syndrome (SLS) were examined by histopathologic and, in some cases, morphometric techniques. Skin biopsy specimens were taken on the volar side of the right forearm below the cubital fossa. The histopathological picture was characterized by a moderate to pronounced hyperkeratosis that could include follicular hyperkeratosis. The stratum granulosum was thickened. There was acanthosis and usually some papillomatosis. These observations were in accordance with the morphometric measurements. There was often a slight, chronic infiltrate in the upper dermis. The ichthyosis in SLS can be included in the recessively inherited, congenital group, with a seemingly lower tendency to parakeratosis.