A case of pachydermodactyly in a seventeen year old associated with repetitive minor trauma.

A boy presented initially to a Rheumatology clinic with a three year history of asymptomatic swelling of the third to fourth proximal interphalangeal (PIP) joints bilaterally. A presumptive diagnosis of seronegative arthritis was made. Sulfasalazine was commenced without improvement and resulted in mood disturbance. Blood tests including ESR, lupus anticoagulant, rheumatoid factor and CCP antibodies were unremarkable. Hand radiographs were normal. MRI showed oedema within soft tissues around PIP joints. His care was transferred to the Rheumatology unit in our hospital and the rheumatological diagnosis was revised; sulfasalazine was stopped and skin biopsy organised. Onward referral to Dermatology was made. Examination revealed symmetrical swelling and thickening of soft tissues on PIP joints with no evidence of joint synovitis. He denied habitual behaviour but was noted to rub his fingers subconsciously. With this as a cause of repetitive minor trauma, a clinical diagnosis of pachydermodactyly was made. Skin biopsy was supportive showing a dermis with coarse collagen. Pachydermodactyly is rare. This case highlights the importance of prompt recognition to avoid invasive and excessive diagnostic procedures as well as unnecessary immunosuppression.

Spontaneous resolution of keratoacanthoma centrifugum marginatum.

Keratoacantnoma centrifugum marginatum (KCM) is a rare variant of keratoacantnoma, with > 40 cases reported world wide. Spontaneous resolution of KCM is very rare. To our knowledge, this is the first case of KCM with spontaneous resolution as documented by serial photographs.

Enterobious vermicularis (pinworm) infestation of the vulva: report of 2 cases of a pseudoneoplastic lesion mimicking squamous carcinoma.

Enterobious Vermicularis (pinworm) infestation outside the gastrointestinal tract is rare. We report 2 patients with vulval involvement, one of whom presented with a clinically suspicious, rapidly growing mass. The histology of both lesions showed similar features of epidermal proliferation in the form of hyperkeratosis, acanthosis, and papillomatosis; this pseudoepitheliomatous hyperplasia raised the possibility of a well-differentiated squamous carcinoma. There was associated inflammation in both cases, including large numbers of eosinophils in 1 case. On the surface or within the keratin layer, structures with the morphology of enterobious vermicularis eggs were identified. In reporting this unusual pseudoneoplastic phenomenon, we stress the necessity for the pathologist to consider and look for parasites in proliferative squamous lesions of the vulva, especially when there is an associated inflammatory infiltrate rich in eosinophils.

Mutation analysis in Irish families with glomuvenous malformations.

BACKGROUND: Glomuvenous malformations (GVMs) are rare bluish lesions that can affect the skin and mucosal surfaces. They represent defects in vasculogenesis. Lesions can occur sporadically or in an autosomal dominant mode of inheritance. Recent studies have shown that mutations in the glomulin gene (GLMN) on chromosome 1p21-22 are responsible for familial GVMs. OBJECTIVES: To search for mutations in GLMN in Irish families with GVMs. METHODS: We identified four Irish families with GVMs and confirmed linkage to chromosome 1p21-22 in these cases. We sequenced the glomulin gene in all affected and unaffected members of the families. Results Linkage analysis showed that affected individuals from the families shared a common haplotype. Mutation analysis revealed a delAAGAA mutation in exon 3 of the glomulin gene in all four families with GVMs. CONCLUSIONS: We confirm that mutations in the glomulin gene are responsible for GVMs and suggest a founder Irish mutation in the glomulin gene in four Irish families.

Expert system support using a Bayesian belief network for the classification of endometrial hyperplasia.

Accurate morphological classification of endometrial hyperplasia is crucial as treatments vary widely between the different categories of hyperplasia and are dependent, in part, on the histological diagnosis. However, previous studies have shown considerable inter-observer variation in the classification of endometrial hyperplasias. The aim of this study was to develop a decision support system (DSS) for the classification of endometrial hyperplasias. The system used a Bayesian belief network to distinguish proliferative endometrium, simple hyperplasia, complex hyperplasia, atypical hyperplasia and grade 1 endometrioid adenocarcinoma. These diagnostic outcomes were held in the decision node. Four morphological features were selected as diagnostic clues used routinely in the discrimination of endometrial hyperplasias. These represented the evidence nodes and were linked to the decision node by conditional probability matrices. The system was designed with a computer user interface (CytoInform) where reference images for a given clue were displayed to assist the pathologist in entering evidence into the network. Reproducibility of diagnostic classification was tested on 50 cases chosen by a gynaecological pathologist. These comprised ten cases each of proliferative endometrium, simple hyperplasia, complex hyperplasia, atypical hyperplasia and grade 1 endometrioid adenocarcinoma. The DSS was tested by two consultant pathologists, two junior pathologists and two medical students. Intra- and inter-observer agreement was calculated following conventional histological examination of the slides on two occasions by the consultants and junior pathologists without the use of the DSS. All six participants then assessed the slides using the expert system on two occasions, enabling inter- and intra-observer agreement to be calculated. Using unaided conventional diagnosis, weighted kappa values for intra-observer agreement ranged from 0.645 to 0.901. Using the DSS, the results for the four pathologists ranged from 0.650 to 0.845. Both consultant pathologists had slightly worse weighted kappa values using the DSS, while both junior pathologists achieved slightly better values using the system. The grading of morphological features and the cumulative probability curve provided a quantitative record of the decision route for each case. This allowed a more precise comparison of individuals and identified why discordant diagnoses were made. Taking the original diagnoses of the consultant gynaecological pathologist as the 'gold standard', there was excellent or moderate to good inter-observer agreement between the 'gold standard' and the results obtained by the four pathologists using the expert system, with weighted kappa values of 0.586-0.872. The two medical students using the expert system achieved weighted kappa values of 0.771 (excellent) and 0.560 (moderate to good) compared to the 'gold standard'. This study illustrates the potential of expert systems in the classification of endometrial hyperplasias.

Massive abdominal and pelvic myxoma in Carney's syndrome.

This report describes a massive abdominal and pelvic myxoma in a patient with Carney's syndrome. A 38 year old woman presented with abdominal distension and a palpable mass, and at operation a large pelvic and abdominal tumour was identified and resected. The surgical specimen consisted of a lobulated mass, which on cut section had a uniform gelatinous consistency. The mass surrounded both ovaries, the appendix, and the upper part of the uterus, but macroscopically did not appear to involve these organs. Histological examination showed plump stellate and spindle shaped cells set in an abundant myxoid stroma, in keeping with a myxoma. Immunohistochemical staining revealed positivity of tumour cells for vimentin, but no reactivity to desmin, alpha-smooth muscle actin, S-100 protein, CD34, or AE1/AE3. This is the first documented case of massive adominal and pelvic myxoma in a patient with Carney's syndrome. Clinicians and pathologists should be aware that myxomas in Carney's syndrome can rarely involve unusual sites other than the skin and heart.

Uterine adenolipoleiomyoma: a rare hamartomatous lesion.

An apparently unique intramural uterine lesion is described for which we propose the name adenolipoleiomyoma. On gross examination, a well-circumscribed white intramural mass contained focal fatty areas. Histology showed the mass to be composed of smooth muscle, adipose tissue, and endometrial, endocervical, and tubal type glands. The endometrial glands were surrounded by typical endometrial stroma. There was no evidence of adenomyosis in the uterus outside the lesion. This is only the second report of such a lesion within the uterus and the first with an intramural location. We believe it to be a benign hamartomatous lesion.

Polypoid uterine lesions mimicking endometrial stromal sarcoma.

Two polypoid submucosal uterine lesions were examined histologically and immunohistochemically with monoclonal antibodies to desmin and alpha smooth muscle actin. One case comprised a leiomyoma and the other a polypoid form of adenomyosis. Both polyps had prolapsed through the external cervical os. The lesions had an ulcerated surface with focal areas of marked increased cellularity and pronounced vascularity throughout, such that they mimicked a low grade endometrial stromal sarcoma infiltrating the myometrium. The cellular areas showed diffuse positivity for desmin and alpha smooth muscle actin, confirming them to be of smooth muscle origin. The changes of marked hypercellularity and pronounced vascularity within polypoid submucosal uterine lesions have not been emphasised in published reports up to now. Pathologists should be aware of these morphological features in order to avoid misdiagnosis of such cases as endometrial stromal sarcomas. The changes described here are likely to be secondary to trauma associated with a polypoid lesion prolapsing through the external cervical os.

Anaplastic large cell malignant lymphoma with extensive eosinophilic or neutrophilic infiltration.

AIMS: We describe the clinicopathological features of eight cases of Ki-1 positive anaplastic large cell malignant lymphoma (Ki-1 ALCL) in which there was extensive infiltration by eosinophils and/or neutrophils in the absence of necrosis. METHODS AND RESULTS: The patients comprised four males and four females with an age range of 24-74 years. Five cases had originally been diagnosed as Hodgkin's disease and one as true histiocytic lymphoma. In all cases, there was massive infiltration by eosinophils and/or neutrophils sometimes to such an extent that malignant cells were obscured. Immunohistochemical staining was performed using the monoclonal antibodies CD30, CD15, CD45, CD20, CD3, CD45RO, epithelial membrane antigen (EMA), CAM5.2, vimentin and CD68. In all cases, tumour cells were strongly positive for CD30 but negative for CD15. One case was positive for CD45 but none expressed B or T-cell markers. Five cases were positive for vimentin and two for EMA. Three of seven patients in whom adequate clinical details were available had stage III or IV disease at presentation and four exhibited B symptoms. Four patients had a peripheral neutrophilia and one a peripheral eosinophilia. CONCLUSIONS: The study shows that an eosinophil and/or neutrophil-rich variant of Ki-1 ALCD exists, expanding the morphological spectrum of this tumour.

Inter- and intra-observer variation in the histopathological reporting of cervical squamous intraepithelial lesions using a modified Bethesda grading system.

OBJECTIVE: 1. To assess inter- and intra-observer variation in the histopathological reporting of cervical colposcopic biopsies using a histologic modification of the cytological Bethesda grading system; 2. to determine the histologic profile of those cases which resulted in diagnostic disagreement. METHODS: Consecutive cervical colposcopic biopsies (n = 125) were assessed independently by six experienced histopathologists. Cases were classified as normal, low grade squamous intraepithelial lesion or high grade squamous intraepithelial lesion. Six months later the process was repeated. The degree of inter and intra-observer variation was assessed by kappa statistics. All cases in which there was less than perfect inter and intra-observer agreement were reviewed by the coordinator of the study. RESULTS: In the first round of the study inter-observer agreement was generally poor, with unweighted and weighted kappa values ranging from 0.15 to 0.58 (average 0.30) and from 0.21 to 0.61 (average 0.36) respectively. In the second round inter-observer agreement was better, with unweighted and weighted kappa values ranging from 0.08 to 0.55 (average 0.33) and from 0.22 to 0.59 (average 0.42). Ten of the 15 pairs of observers achieved fair inter-observer agreement using weighted kappa analysis. The degree of intra-observer agreement was better, unweighted and weighted kappa values ranging from 0.26 to 0.61 (average 0.47) and from 0.34 to 0.62 (average 0.51) respectively. Two of the six participants achieved fair intra-observer agreement and two achieved good intra-observer agreement using weighted kappa analysis. There were marked difficulties in the separation of normal squamous epithelium from low grade squamous intraepithelial lesion and in the separation of low grade from high grade squamous intraepithelial lesions. Histopathological review revealed that many of the difficulties in the separation of normal and low grade squamous intraepithelial lesion were in the distinction between superficial vacuolated cells and true koilocytes. Difficulties also resulted in the separation of basal cell hyperplasia, inflammatory associated changes and immature squamous metaplasia from low grade squamous intraepithelial lesion. Conditions which resulted in difficulty in the separation of low grade and high grade squamous intraepithelial lesions included florid koilocytotic change and immature metaplastic squamous epithelium with atypia. In some cases, there was a full spectrum of diagnoses from normal to high grade squamous intraepithelial lesion. These were largely cases of immature metaplastic squamous epithelium with atypia and of thin or atrophic squamous epithelium with atypia. CONCLUSIONS: Most pairs of observers can achieve fair inter-observer agreement in the reporting of cervical colposcopic biopsies using a modified Bethesda system. Intra-observer agreement is also generally fair to good using this system. It may be that a two tier grading system is more appropriate for the histopathological reporting of these biopsies than the traditional three-tier intraepithelial neoplasia (CIN) system.

Childhood discoid lupus erythematosus: a report of two cases.

Discoid lupus erythematosus (DLE) is an uncommon disease in childhood. We present two patients initially diagnosed as impetigo and photosensitive eczema with impetigo, respectively, who failed to respond to topical and systemic antistaphylococcal agents and in whom a diagnosis of discoid lupus erythematosus subsequently became apparent.

Autosomal recessive inheritance of erythrokeratoderma variabilis.

Erythrokeratoderma variabilis is a rare genodermatosis conventionally regarded as autosomal dominant in inheritance. We describe the clinical features and light and electron microscopic findings in two affected siblings born to unaffected parents and suggest an autosomal recessive mode of inheritance in this family. We also briefly review the literature on this disorder.