J. Toonstra

Primary cutaneous large cell lymphomas of follicular center cell origin: A clinical follow-up study of nineteen patients

In this study the clinical characteristics and follow-up data of nineteen patients with a diffuse large cell lymphoma of follicular center cell (B cell) origin, with only skin lesions at presentation, are reported. Sixteen of nineteen patients came to us with localized nodules or tumors, preferentially on the trunk, scalp, and lower legs. Remarkably, eight of eleven patients with disease confined to a limited area on the trunk had a history of slowly progressive papular lesions that had been present for 1 to 20 years prior to the development of rapidly growing skin tumors. Initial treatment, generally radiotherapy and/or polychemotherapy, resulted in complete remissions in seventeen of nineteen patients. Only three patients developed extracutaneous disease, whereas two other patients had recurrent disease in the skin at sites distant from the original skin lesions. Excluding three patients who had just finished initial treatment at the time of writing, twelve of sixteen patients were currently alive and in complete remission with a median survival of 44 months. Four patients died, three of whom were elderly women who had skin tumors on the lower legs when first seen. These results suggest that patients with a primary cutaneous large cell lymphoma of follicular center cell origin with disease confined to the trunk of scalp have a very favorable prognosis.

Cutaneous immunocytomas: a clinicopathologic study of 26 cases

The clinical and histological features of 16 patients with a primary cutaneous immunocytoma and 10 patients with a secondary cutaneous immunocytoma are reported. In all cases the diagnosis was based on the presence of monotypic plasma cells or lymphoplasmacytoid cells. Our data show that primary cutaneous immunocytomas are a distinct type of cutaneous lymphoma, characterized by (a) the presence of solitary or localized skin lesions (13 of 16 cases); (b) preferential localization on arms and legs (15 of 16 cases); (c) excellent response to local treatment (15 of 16 cases) and (d) a favourable prognosis. Histologically, these primary cutaneous immunocytomas are characterized by the presence of nodular or diffuse infiltrates with monotypic lymphoplasmacytoid/plasma cells located at the periphery of the infiltrates. Important clinical and histological differences were noted between primary and secondary immunocytomas. In the latter group more widespread skin disease was seen, often in the presence of paraproteins and/or autoimmune diseases. In contrast with the peripheral localization of the monotypic cells in primary cutaneous immunocytomas the monotypic lymphoplasmacytoid/plasma cells in secondary immunocytomas formed diffuse infiltrates or these cells were found dispersed throughout the infiltrate. There were no differences in clinical presentation or course between the different subtypes of cutaneous immunocytomas (lymphoplasmacytic, lymphoplasmacytoid and polymorphic immunocytomas). The differential diagnosis between primary cutaneous immunocytomas and cutaneous plasmacytomas, primary follicular centre cell lymphomas and cutaneous ‘pseudolymphomas’ is discussed.

Photosensitivity in patients with lupus erythematosus: a clinical and photobiological study of 100 patients using a prolonged phototest protocol

Summary Background There is a clear relationship between ultraviolet (UV) radiation (UVR) and the clinical manifestations of patients with lupus erythematosus (LE). Cutaneous lesions are induced or exacerbated by exposure to UVR. Of patients with LE, 24–83% are reported to be photosensitive to UVR. LE tumidus appears to be the most photosensitive subtype of LE, followed by subacute cutaneous LE (SCLE). In general, the history of patients with LE correlates poorly with the presence or absence of photosensitivity, due to a delayed time interval between UV exposure and exacerbation of skin lesions. Phototesting using artificial UVR and visible light is a reliable way of diagnosing photosensitivity.

Granulomatous slack skin. Report of three patients with an updated review of the literature.

Purpose: Granulomatous slack skin (GSS) is a rare cutaneous disorder characterized clinically by the evolution of circumscribed erythematous lax skin masses, especially in the body folds, and histologically by a granulomatous T-cell infiltrate and loss of elastic fibers. GSS is often associated with preceding or subsequent lymphoproliferative malignancies, especially mycosis fungoides (MF) and Hodgkin’s disease (HD). No effective treatment is known yet. Whether this entity is a benign disorder, a peculiar host reaction to a malignant lymphoma, a precursor of malignant lymphoma or an indolent cutaneous T-cell lymphoma (CTCL) in itself is still a matter of debate. Patients and Methods: The results of the patients with GSS from the Netherlands are compared with the cases reported in the world literature. Results: A female patient had had GSS for 8 years without developing a secondary malignancy. In a second female patient with a histologically confirmed diagnosis of MF, GSS developed 18 years later in the axillary and inguinal folds which had previously been affected by plaque-stage MF lesions. A third male patient with a 6-year history of erythematosquamous skin disease diagnosed as CTCL developed GSS. Moreover, granuloma formation was also found in a facial basal cell carcinoma, in a cervical lymph node and the spleen. Clonal rearrangements of the T-cell receptor β genes were found in the 2 female patients; the male patient could not be tested. Conclusion: GSS is a rare clinicopathological entity. Only 34 patients have been described so far. The development of GSS within plaque MF lesions has not been reported before. Our third case developed very extensive skin lesions and showed a strong propensity to develop granulomas as compared to cases reported before. The presence of a clonal T-cell population was demonstrated in all cases tested. Our cases support the idea that GSS is a very rare and rather indolent type of CTCL. Apparently, the disease is associated with a peculiar immune response, characterized by granuloma formation and disappearance of elastic fibers resulting in the lax skin. The relationship between GSS and other preexisting or subsequent lymphoproliferative diseases (diagnosed in approximately 50% of the cases) warrants a life-long follow-up.

Actinic reticuloid: A clinical, photobiologic, histopathologic, and follow-up study of 16 patients

We report a detailed clinical, histopathologic, and photobiologic study of 16 Dutch patients with actinic reticuloid. All were middle-aged or elderly men who had persistent plaques on light-exposed skin only (two patients), extension of lesions to nonexposed areas (four patients), or prolonged or persistent episodes of erythroderma (10 patients). They were sensitive to UVB, UVA, and visible light. In 10 of 13 patients tested, the dermal infiltrate contained predominantly suppressor T cells. Many also had a reversed helper-suppressor T cell ratio. Circulating lymphocytes with deeply indented nuclei were present in all but were most pronounced in the most photosensitive erythrodermic patients. Tolerance induction therapy with UVB irradiation produced an excellent or good response in 13 of 15 patients. One patient responded to cyclosporine therapy.

Erythroderma: A clinical and follow-up study of 102 patients, with special emphasis on survival

BACKGROUND Erythroderma may result from different causes. There have been no publications on this subject with special emphasis on survival. OBJECTIVE The aim of the study was to determine the cause of the erythroderma and the prognosis of these patients. METHODS Clinical and follow-up data from 102 patients with erythroderma were analyzed. We estimated survival of patients with erythroderma, from causes other than Sézary syndrome, mycosis fungoides, or leukemia cutis. The survival was compared with that of an age-matched control group of the general population. RESULTS The main cause of erythroderma was exacerbation of a preexisting dermatosis (53%). Drug reactions were rarely the cause (5%). A high proportion of the patients had chronic actinic dermatitis/actinic reticuloid (12%). Survival of men with erythroderma was significantly lower than that of the general population. CONCLUSION Men with erythroderma, from causes other than Sézary syndrome, mycosis fungoides, or leukemia cutis, have a lower survival than men in the general population.

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

SummaryAn 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.Experience has proven that the doses for acute affects in man and mouse are at least proportional to human tanning doses. Comparison of the doses of UV-A and UV-B required for the induction of tumors and for acute reactions of the skin, therefore, leads to the conclusion that the carcinogenic risks of tanning by UV-A and of tanning by UV-B are in the same order of magnitude.

Lymphomatoid papulosis in children: a study of 10 children registered by the Dutch Cutaneous Lymphoma Working Group

Lymphomatoid papulosis (LyP) is a chronic recurrent self‐healing condition, with histological features suggestive of a malignant lymphoma. Only a few cases have been described in children. We report 10 children with this skin disease and compare them with the adult type of LyP and childhood cases described in the literature. Although LyP has the same clinical picture and histology in both age groups, in contrast with the adult type no transformation into malignancy has been described in childhood.

Proposal for updating the pseudoxanthoma elasticum classification system and a review of the clinical findings

Pseudoxanthoma elasticum (PXE) is a systemic disorder affecting elastic tissues most markedly in skin, retina, and blood vessels. It is caused by mutations in the ABCC6 gene and is transmitted in an autosomal recessive fashion. In 1994 a new classification system for PXE was published as the result of a consensus conference. Since then the ABCC6 gene has been discovered. We propose that there is a need for a classification system incorporating all relevant systemic symptoms and signs, based on standardized clinical, histological, and molecular biological examination techniques. We re‐evaluated the histopathologic PXE signs and propose a classification system with unambiguous criteria leading to a consistent diagnosis of definitive, probable, or possible PXE world‐wide. We put this proposed classification forward to encourage further debate on the diagnosis of this multi‐organ disorder.

Mammary Paget's disease confined to the areola and associated with multifocal Toker cell hyperplasia

A hitherto unreported variant of mammary Pagets disease (MPD) limited to the areola, leaving the nipple unaffected, has been analyzed by serial sectioning of the whole areola and nipple. This otherwise characteristic MPD proved to be confined to the epidermis. There was no underlying carcinoma. This MPD was associated with a multifocal presence of monomorphic but otherwise similar cells in small collections surrounding the ostia of areolar mammary glands in the clinically unaffected area. This condition was interpreted as hyperplasia of mammary gland-related cells also found in normal nipples (so-called Toker cells). The observations hint at a possible derivation of some cases of mammary and extramammary Pagets disease from such Toker cells.