bcl-2 protein expression in primary cutaneous large B-cell lymphoma is site-related.

PURPOSE: Primary cutaneous large B-cell lymphoma (PCLBCL) that presents on the leg has recently been recognized as a distinct disease entity. These lymphomas have a reduced disease-free survival and a worse prognosis as compared with the more common, morphologically similar PCLBCL that present on the head or trunk. Studies in noncutaneous diffuse large B-cell lymphomas suggest a relationship between the expression of bcl-2 protein and clinical behavior. In the present study, we investigated whether these two groups of PCLBCL differ in the expression of bcl-2 protein and the presence of t(4;18), known as one of the causes of bcl-2 overexpression. PATIENTS AND METHODS: Paraffin sections from pretreatment biopsies of 14 PCLBCLs of the head or trunk and nine PCLBCLs of the legs were investigated for expression of bcl-2 protein using immunohistochemistry, and for the presence of the 14;18 translocation using polymerase chain reaction (PCR) amplification with primers against both the major breakpoint region (mbr) and the minor cluster region (mcr) of bcl-2. For reasons of comparison, nine secondary cutaneous large B-cell lymphomas (SCLBCLs) were also studied. RESULTS: Expression of bcl-2 protein was found in all nine PCLBCLs of the leg and in all nine SCLBCLs, but not in any of the 14 PCLBCLs on the head and trunk. The t(14;18) was only detected in two of seven SCLBCLs, but not in the five PCLBCLs of the leg or the eight PCLBCLs on the head or trunk studied. CONCLUSION: The striking differences in bcl-2 expression between PCLBCL of the head or trunk and PCLBCL on the leg suggest that bcl-2 expression is site-related and may contribute to the different clinical behavior between these two groups of lymphomas. In addition, they underscore that PCLBCL on the head and trunk and PCLBCL on the leg are distinct disease entities, as recently recognized in the European Organization for Research and Treatment of Cancer (EORTC) classification for primary cutaneous lymphomas.

Pulmonary amyloidoma. Histologic proof yielded by transthoracic coaxial fine needle biopsy.

Nodular pulmonary amyloidosis was diagnosed by percutaneous transthoracic fine needle biopsy specimen in an 88-year-old woman. Congo red staining should be performed whenever band-like hyalinized material is obtained on aspiration of a solitary nodule. Dense calcifications can occur in pulmonary amyloidomas. In selected cases, fine needle biopsy appears to be preferable to transbronchial forceps biopsy since the risk of a possibly life-threatening pulmonary hemorrhage may be lower.

Aberrant immunophenotypes in mycosis fungoides.

Skin biopsy specimens from 40 patients with mycosis fungoides (MF) were examined by a selective procedure for the assessment of immunophenotypic deviation. In 19 cases (48%), aberrant phenotypes were detected. Type and degree of aberration differed greatly without apparent clinicopathologic correlation. Different phenotypes in the same patient occurring either simultaneously or during the course of the diseases were observed. Phenotypic aberration showed a statistically significant correlation with tumor stage MF, the large cerebriform tumor cell type, blast cell transformation, and diffuse dermal infiltration. In combination with longer-existing disease, more lymph node and visceral involvement and a higher mortality rate of MF in the aberrant group indicated an association with advanced disease. Its prognostic relevance for the individual patient, however, seemed limited because of the association of aberration and a long-lasting indolent course in many other patients. The assessment of phenotypic aberration formed a valuable contribution to the diagnosis of MF, especially in cases with little cellular atypia.

The diagnostic value of morphometry on blood lymphocytes in erythrodermic actinic reticuloid.

BACKGROUND: As the differential diagnosis of erythrodermic actinic reticuloid vs Sézary syndrome (SS) can be very difficult, we examined the value of the nuclear contour index (NCI) on blood lymphocytes as the criterion for differential diagnoses. The NCI is defined as the nuclear parameter divided by the square root of the nuclear area. Three different parameters were studied: mean NCI, percentage of cells with an NCI of 6.5 or greater, and the highest NCI. These indexes were studied on blood lymphocyte samples obtained from 10 patients with erythrodermic actinic reticuloid and were compared with the findings in 10 patients with other benign forms of erythroderma and in seven patients suffering from SS. RESULTS: The patients with erythrodermic actinic reticuloid differed significantly from the group with SS regarding the percentage of cells with an NCI of 6.5 or greater and the highest NCI, but not when the mean NCI was considered. All three parameters revealed nonsignificant results for erythrodermic actinic reticuloid compared with other benign forms of erythroderma. The group with SS differed significantly from the patients with other benign forms of erythroderma regarding all three parameters. By combining three morphometric criteria (mean NCI, > or = 5.5; > 30% lymphoid cells with an NCI of > or = 6.5; and highest NCI, > or = 11.5), all patients with erythrodermic actinic reticuloid or other benign forms of erythroderma and six of the seven patients with SS were correctly classified. CONCLUSION: Our data indicate that assessment of the NCI on peripheral blood lymphocytes is of value in the differential diagnosis of erythrodermic actinic reticuloid vs SS.

Jessner's lymphocytic infiltration of the skin. A clinical study of 100 patients.

Jessner's lymphocytic infiltration of the skin is a well-known but poorly understood disorder. Some doubt still exists about whether it is a single entity or a heterogeneous group that can pass into polymorphous light eruption, discoid lupus erythematosus, or even malignant lymphoma. Therefore, a large number of patients with lymphocytic infiltration of the skin (N = 100; 46 male, 54 female) were examined to elucidate these questions. We conclude that lymphocytic infiltration of the skin is a single entity. Progression into polymorphous light eruption, discoid lupus erythematosus, or lymphoma was not observed. However, this study shows that lymphocytic infiltration of the skin and polymorphous light eruption cases occur simultaneously in 1 patient. In this study the cases of 10 patients with this combination are reported. An effective but harmless therapy is yet unknown. Intermittent use of topical steroids can be useful but is not effective in many patients.

UVA-induced tumours in pigmented hairless mice and the carcinogenic risks of tanning with UVA.

An animal experiment is presented in which two groups of pigmented hairless mice were exposed daily to suberythemal doses of UVA to study tumourigenesis. The aim of the study was to estimate the carcinogenic risks of tanning by UVA. The pigmented hairless mice, Skh-hr2, were separated by selective breeding into two groups, the "browns" and the "blacks". Both groups were exposed daily to UVA from fluorescent UVA lamps (Philips TL40W/09) purified by rigorously filtering out the shorter wavelengths. No acute actinic damage was observed after any exposure. However, in most UVA exposed animals, especially in the blacks, a marked scratching preceded the development of tumours. Hyperkeratosis was also observed. All animals developed tumours. Histopathologically at least 60% of the tumours were squamous cell carcinomas. Depositions of melanophages were observed, but no melanomas. It is beyond any doubt that UVA is carcinogenic in laboratory animals. The present state of knowledge justifies no preference for tanning with UVA over tanning with UVB.

Immunocytoma of the skin simulating lymphadenosis benigna cutis.

We report a case of primary cutaneous lymphoma, of the lymphoplasmacytoid type (immunocytoma), in which a small neoplastic component was obscured by a dominating reaction exhibiting characteristic features of lymphadenosis benigna cutis. This abnormal cell population was identified because of the unusual cytomorphology of the tumor cells, which showed deeply indented nuclei in combination with a distinctly plasmacytic cytoplasm. Monoclonality was revealed by the cytoplasmic positively of the tumor cells for lambda chains only. This case strongly suggests that in at least a number of cases of lymphadenosis benigna cutis, a low-grade malignant lymphoma may be present.

The carcinogenic risks of modern tanning equipment: is UV-A safer than UV-B?

An animal experiment is presented in which three groups of albino hairless mice (Skh-hr 1) were exposed to daily doses of either UV-B or UV-A to study carcinogenesis. The UV-A was filtered carefully so as to eliminate contaminating UV-B. The doses required for acute effects (erythema and edema) were also determined for the two radiation modalities. In order to study the relative carcinogenic risks of exposures to UV-A and to UV-B, for both modalities, the doses causing skin tumors were compared to the doses required for eliciting acute effects in the skin. In the experiment on carcinogenesis all animals developed tumors, the ones exposed to UV-A as well as the ones exposed to UV-B. A striking difference, however, was that the induction times of the first tumors showed a larger spread in the mice exposed to UV-A than in the UV-B groups. Also, the development of successive tumors in each individual mouse was more spread in time in the UV-A group. A second difference between the effects on the skin was that in the animals exposed to UV-B no skin reactions were seen until the tumors developed. However, in most UV-A exposed animals, a marked scratching, probably caused by severe itching, and hyperkeratosis preceded the development of the tumors. Histologically at least 60% of the larger tumors induced by UV-A appeared to be squamous cell carcinomas. This finding is very similar for UV-B induced tumors. The elastic fibers in the UV-A exposed animals were also examined and actinic elastosis was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Sézary syndrome with early immunoblastic transformation.

Two patients with clinical manifestations of Zézary syndrome are reported. In both cases from an early stage of the disease in addition to characteristic Sézary cells large numbers of immunoblasts were present in skin lesions and peripheral lymph nodes and in one case also in the blood. Their relationship to the characteristic Sézary cells was shown by morphological, cytochemical and immunological methods. The infiltrates in the skin were epidermotropic in one case and nonepidermotropic in the other. Lymph node structure was effaced by diffuse infiltration of abnormal lymphoid cells. These were found to proliferate in the skin as well as in lymph nodes. Cytogenetical studies of blood lymphocytes indicated an abnormal hypodiploid clone in both cases. Immunologically the tumour cells had properties of peripheral T-lymphocytes but whereas all abnormal cells exhibited inducer/helper cell characteristics in one case, only a minority of the lymphocytes revealed these characteristics in the other case. In this case the tumour cell population changed into a more pleomorphic type. The classification of the cases is discussed.

The small-cell variant of mycosis fungoides. A clinicopathological and quantitative electron microscopic study on 14 patients.

Small-cell variants of Sézary syndrome and mycosis fungoides (MF) have been described. However, in these studies the nuclear area of the small-cell variant of MF (SC-MF) as compared to histological classical MF (CL-MF) was not characterized objectively by quantitative electron microscopy. In a 14-year follow-up period, of a total of 76 patch/plaque stage MF patients seen in the Department of Dermatology of the University Hospital Utrecht, 14 (18%) had an infiltrate composed of atypical lymphocytes characterized by a distinctly smaller cell diameter and smaller, hyperchromatic, deeply indented nuclei as compared to the usual cell type of MF. The aim of the investigation was to confirm this observation objectively using quantitative electron microscopy (morphometry) and to define SC-MF as compared to CL-MF. The study was performed on the 14 patients with SC-MF, and 10 patients with clinical and histological CL-MF and 4 patients with chronic eczema. Electron micrographs of sections obtained from each biopsy were analysed by computer to produce the following data: a nuclear contour index (NCI), the mean nuclear area (MNA), the mean nuclear area of the cells above the 75th percentile (P75NA) and the percentage of cells larger than 30 microm2. The values of MNA differed significantly between patients with SC-MF and those with CL-MF (17.6 vs 23.2 microm2; P = 0.02), as did the values of P75NA (20.7 vs 27.9 microm2; P = 0.01). The NCI of the SC-MF and CL-MF patients were similar. These results are consistent with our observations that SC-MF does indeed exist.

Actinic reticuloid simulating Sézary syndrome. Report of two cases.

A report is given on two male patients who showed all the main characteristics of Sézary syndrome (SS). When phototested, however, they proved to be extremely photosensitive, which suggested a diagnosis of actinic reticuloid (AR). This was supported by the predominance in blood and skin specimens of lymphoid cells with a suppressor/cytotoxic phenotype, the absence of clonal cell proliferation and a benign clinical course. Differential diagnostic problems of SS and erythrodermic AR are discussed.

Dermatography, a treatment for sequelae after head and neck surgery: a case report.

Two patients with discolouration fo skin grafts after head and neck surgery, were treated with dermatography, a refined method of tattooing, and with intra-cicatricial keloidectomy, of which the results are described.

Normal and abnormal development of the anorectum.

A study of the development of hereditary anorectal malformations in pig embryos resulted in major corrections of all current theories concerning normal and abnormal anorectal development. The principal event in anorectal development proved to be a shift of the dorsal part of the cloaca and the adjacent gut to the body surface of the tail groove. Regression of the dorsal part of the cloacal membrane forms an essential part in this process. Agenesis of this part to the membrane blocks the normal shift of the anorectum of the body surface with anorectal malformation as the result. The subtype of anomaly appeared to depend on the size and the form of this defect. Thus, small defects resulted in stenotic, ectopic perineal, and vulvar/vestibular orifices, and larger defects led to anal and anorectal agenesis. In all cases, an ectopic anal communication ("fistula") to the skin or the urogenital system developed but this was eventually lost in some cases by epithelial regression. A basic similarity between man and pig in both the normal development of the anorectum and in the morphology of the anorectal anomalies makes it likely that the same pathogenetic principle also applies to man. Deformities of the cloacal membrane may also form the basis of other congenital malformations of cloaca-derived orifices such as hypospadia, epispadia, vesical and cloacal extrophy, double urethra, and cloacal membrane agenesis.

Congenital hereditary lymphedema in the pig.

A histopathological investigation was performed in newborn pigs with congenital hereditary lymphedema. The edema varied greatly in degree and extension. Although mostly confined to the hind legs it may involve other parts of the body, and even attain a most severe generalized distribution. It was found due to malformations of the lymphatic system which were general in character in all animals irrespective the grade in their edema. Parallel to the grade of edema however, these lymphvascular abnormalities varied from minor hypoplasia and localized aplasia to a complete agenesis of the whole lymphatic system.

The pathogenesis of congenital hereditary lymphedema in the pig.

The morphogenesis of congenital hereditary lymphedema was studied in pigs. The disorder, which is essentially a general underdevelopment or even total non-development of the lymphatic system proved to be present during the whole period of lymphatic development. It is suggested that a retardation in the differentiation of the lymphatic primordia from the primitive veins is the early event regulated by a chromosomal aberration. The longer this delay the more serious the lymphatic malformations.