Sebastian C.J. van der Putte

Increased number of immunoreactive nerve fibers in atopic dermatitis

The presence of immunologic markers for neurofilaments, neuropeptides of sensory nerve fibers (Calcitonin gene-related peptide and substance P), for noradrenergic innervation (neuropeptide Y and Tyrosine hydroxylase), and Neuron-specific protein 9.5 was evaluated in frozen tissue sections from normal skin (n = 34) and from skin biopsies manifesting urticaria (n = 6), leukocytoclastic vasculitis (n = 4), systemic lupus erythematosus (n = 23), and atopic dermatitis (n = 40, of which 16 were from lesions induced by epicutaneous atopic allergen patch tests). In some normal skin specimens immunoreactive nerve fibers expressing Neuron-specific protein 9.5 were observed in the epidermis, dermis, and around blood vessels. For the other markers, immunolabeling was mainly observed in the dermis around blood vessels. Neurofilaments, which are scarce in normal skin epidermis, were present in higher density in the epidermis of affected skin in all disease conditions. Biopsies from urticaria and systemic lupus erythematosus showed a decrease in density of fibers immunolabeled for neuropeptides substance P and Calcitonin gene-related peptide and for Neuropeptide Y. In biopsies from skin with atopic dermatitis, an increased density of fibers was observed for all markers except Neuropeptide Y and Tyrosine hydroxylase. In this group, biopsies from positive atopic allergen patch tests showed an enhanced density of fibers labeled by antibody to Neuron-specific protein 9.5 and a lower density in labeling for Tyrosine hydroxylase. The data indicate a potential role of innervation and neuropeptides in dermatoses like atopic dermatitis.

Cutaneous cylindroma with malignant transformation

Background. Malignant cutaneous cylindroma is a rare tumor. It has been described in 26 cases, both in the solitary form and in the autosomal dominant inherited multiple tumor form. The authors present two new cases that occurred in one family with a history of multiple cylindromas.

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.

Primary B‐cell malignant lymphoma of the maxilla with a sarcomatous pattern and multilobated nuclei

Three cases of primary malignant lymphoma of the maxilla are reported. The primary intraosseous origin of these tumors was demonstrated by x‐ray examination and surgical exploration. The initial interpretation as odontogenic infection led to a delay in starting therapy of 9 months in one case. Biopsies of two cases were initially interpreted as sarcoma because of a dense reactive fibrosis between the tumor cells. Subsequently, hemimaxillectomy was performed in one case. Histologically and ultrastructurally the tumor cells showed marked nuclear abnormalities with cleavage, folding, and lobulation. Immune histochemical studies of two cases showed a monoclonal immunoglobulin expression, IgG‐K; T‐lymphocyte‐associated antigens were not detected on the tumor cells. The findings indicate the existence of a primary B‐cell malignant lymphoma of bone with multilobated nuclei. The lymphoid nature may be masked by a dense proliferation of connective tissue. The relation of these tumors to the classifications for malignant lymphoma of lymph node is discussed.

Cutaneous ‘bronchogenic’ cyst

A case of a congenital ‘bronchogenic’ cyst of the skin over the right scapula of a 4‐year‐old boy is reported. The continuity of its epithelial lining with the epidermis and its appendages is stressed and the consequences of this relationship for current theories about the pathogenesis of cutaneous ciliated cysts are discussed.

p53 and bcl-2 expression do not correlate with prognosis in primary cutaneous large T-cell lymphomas

Overexpression of p53 protein in cutaneous T‐cell lymphoma (CTCL) has been reported in primary cutaneous large T‐cell lymphomas (PCLTCL) and has been associated with tumor progression and transformation in mycosis fungoides. However, the prognostic significance of p53 expression has not been studied thus far. In the present study we investigated the expression of p53 as well as bcl‐2 protein in 27 PCLTCL, including 19 CD30‐positive and 8 CD30‐negative lymphomas, retrieved from the registry of the Dutch Cutaneous Lymphoma Working Group.

UV-B-induced bullous pemphigoid restricted to mycosis fungoides plaques

We describe a 77‐year‐old female patient with plaque‐stage mycosis fungoides (MF) who developed bullous lesions in lesional skin only, while receiving short‐wave ultraviolet radiation (UV‐B) therapy. Histopathological and immunohistochemical examination resulted in a diagnosis of bullous pemphigoid (BP). Withdrawal of the UV‐B treatment and application of a high‐potency topical corticosteroid cream resulted in a rapid regression of the BP. As the bullous lesions were strictly confined to the MF plaques, the cutaneous infiltrate was probably

Cutaneous T-cell lymphoma, multilobated type, expressing membrane differentiation antigens of precursor T-lymphocytes.

Monoclonal antibodies to human T‐cell membrane antigens were used to evaluate the immunological phenotype of the tumour cells in two cases of a recently described cutaneous T‐cell lymphoma of ‘multilobated’ type. In one case the distinctive abnormal blast cells expressed positivity for OKT6, anti‐HTA1, OKT4 and Leu–3a, and showed binding capacity for peanut agglutinin (PNA). These are properties normally displayed by immature cortical thymocytes. The antigen expression of the abnormal blast cells in the other case was OKT3, Leu‐1, OKT4, Leu–3a in the absence of PNA‐binding; these properties bear more resemblance to more mature T‐inducer/helper cells. When combined with consideration of the morphological aspects we suggest that in both cases the abnormal cells represented precursor T‐lymphocytes.

The Development of the Human Anorectum

I read with great interest the article ‘‘Epithelial and muscular regionalization of the human developing anorectum’’ by Fritsch et al. (2007). The study offered a histological description of anorectal development supplemented with data from immunohistochemistry and in situ hybridization. It was a surprise to notice that the observations reported were not correlaing with the results of a recent comprehensive analysis of the development of the human perineum (Van der Putte, 2005). Essential findings such as the important role of the cloaca in the formation of the anorectum were ignored and differences in observation and interpretation were not discussed. The authors divided the developing anorectum into a ‘‘rectal section’’ characterized by a lining of stratified columnar epithelium and an ‘‘anal section’’ lined by nonkeratinizing stratified squamous epithelium. This is in line with the convention which considers the anorectum to be a combination of a rectal segment characterized by columnar epithelium derived from the entodermal hindgut as forerunner of the rectum, and an anal section characterized by squamous epithelium derived from the ectodermal anal pit (Otis, 1905; Ludwig, 1965; Moore and Persaud, 1998; Nievelstein et al., 1998; Larsen, 2001; Davies and Rode, 2006). The authors apparently did not recognize that the caudal part of their ‘‘rectal section’’ has a special character distinctly different from that of the true rectum. It shows a special type of columnar epithelium from which the anal glands originate. Fenger (2007) described that segment in adults as the anal transitional zone (ATZ) which is situated between true rectal mucosa and the ‘‘anal squamous zone’’ (or ‘‘anal section’’ as described by the authors). In his opinion, these two zones together form a specific ‘‘anal canal.’’ This recognition of a specific anal canal correlates well with the findings in the recent investigation into the development of the perineum (Van der Putte, 2005). That study showed the cloaca and its derivatives to be lined by a seemingly multilayered columnar epithelium which proved to be pseudostratified columnar in a test with a confocal laser scan microscope. The epithelium demonstrated reactivety for anti-cytokeratin 7 (Biogenex, San Ramon, CA). This contrasted with unreactivity in colorectal epithelium and epidermis. The lamina propria is dense with a longitudinal orientation. The cloaca-derived mucosa of the developing anal canal remains very similar to the lining of the urogenital sinus. It can be distinguished from the colorectal mucosa in embryos as young as 7 weeks (fertilization age) (21 mm crown-rump length) (Fig. 1a–d). The initially subtle differences, such as a more regular distribution of nuclei and a nucleus-free apical zone in the epithelium and a loosely structured lamina propria in the colorectal mucosa, become more prominent when goblet cells and crypts appear in the colorectal mucosa at about nine-and-a-half-weeks (45 mm) whereas the cloaca-derived mucosa hardly changes. A remarkable and deceptive feature is that a relatively large cranial part of this cloaca-derived segment is from the beginning surrounded by the muscularis propria of the rectum (Fig. 1e). These relations are preserved when the segment undergoes a relative decrease in length later and by forming anal glands homologous to the (bulbo-)urethral and vestibular glands becomes the most characteristic element of the ATZ. Extra support for its cloacal derivation is provided by ano-urogenital communications in the ‘‘high’’ type of anorectal malformation in which this type of mucosa lines the blind-ending anorectum and gradually passes into the same lining in the urogenital structure (Van der Putte, 2006). The morphogenesis of the ‘‘anal section’’ is much more complicated and interesting than described by the authors. They did not mention the close relationship between the pseudostratified columnar ATZ epithelium and the squamous epithelium of their ‘‘anal section.’’ In conventional histology, this relationship is manifested by a vague delineation shortly after its appearance in 7.5-week-old embryos (24 mm; Fig. 1f) and by a tapering extension of ATZ epithelium on top of the squamous epithelium in particular (Fig. 1g). The latter phenomenon has also been illustrated by Otis (1905, Fig. 35) and by Fenger (2007, Fig. 27.3). That configuration suggests a ‘‘creeping cranially’’ of squamous epithelium from perianal epidermis (Jit, 1975) but immunohistochemical tests for cytokeratin 7 not only revealed the expected strong reactivity in the luminal layer of columnar/cuboidal cells but also in variable intensities in the squamous cells (unpublished data) (Fig. 1h). A similar staining pattern occurs in areas of squamous metaplasia in the developing vestibulum and male urethra including the deceptive phenomenon of ‘‘creeping’’ epithelium just inside the orifices of the vestibulum and male urethra. This common pattern and its absence in the deep ano-urogenital communications of anorectal malformations (Van der Putte, 2006) suggest some sort of influence by tissue at the insertion of the cloacal

Familial Jessner's lymphocytic infiltration of the skin, occurring in a father and daughter

Familial occurrence of Jessners lymphocytic infiltration of the skin is reported in a father and daughter. A definitive diagnosis of Jessners disease was greatly facilitated by the presence of large numbers of plasmacytoid monocytes within the dermal infiltrates in both patients. A role for skin‐directed lymphocyte migration is suggested to account for the presence of this peculiar cell type.