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Biomedical subjects

E Calonje

Publications and source records attributed to E Calonje.

At least 73 records · Page 4Linked to original sources

Verrucous carcinoma arising in pseudoepitheliomatous keratotic and micaceous balanitis, without evidence of human papillomavirus.

Pseudoepitheliomatous keratotic and micaceous balanitis (PKMB) is a condition which occurs on the glans penis of older men and may be associated with the development of a verrucous carcinoma. A role for human papillomavirus (HPV) in the aetiology of verrucous carcinoma has been implicated and several different HPV types have been found. We report a 74-year-old man who developed a verrucous carcinoma within an area of PKMB on the glans penis. Using a broad-spectrum polymerase chain reaction technique for identifying HPV, the epidermis of the area of PKMB and of the verrucous carcinoma were examined and no HPV DNA was identifiable. These results suggest that there is no part for HPV in the pathogenesis of PKMB or its transformation to verrucous carcinoma.

Aged↗

CD8-positive juvenile onset mycosis fungoides: an immunohistochemical and genotypic analysis of six cases.

BACKGROUND: Childhood cases of cytotoxic T-cell lymphoma have not been well described. OBJECTIVES: We have undertaken an immunohistochemical and genotypic analysis of patients presenting with juvenile onset mycosis fungoides (MF). PATIENTS/METHODS: Of 10 patients presenting over a 3-year period, six exhibited a CD8-positive phenotype. These six patients were also CD2, CD3 and TIA1 positive, but CD56 negative. Apart from the cytotoxic phenotype, these patients had clinicopathological features that were indistinguishable from ordinary cases of MF, with slowly evolving patches and plaques. Three patients were staged as 1A and three as 1B, with no evidence of nodal or systemic disease. RESULTS: Patients responded well to conventional therapy, with no evidence of disease progression after 3 years follow-up. Epidermotropism was a prominent feature in four of the six cytotoxic cases. In two patients with an equivocal histology the diagnosis was confirmed by the finding of a clonal population, using polymerase chain reaction/single strand conformational polymorphism analysis of the T-cell receptor gamma gene in lesional skin. The same technique revealed that all blood samples analysed were polyclonal. CONCLUSIONS: These data show that cytotoxic T-cell lymphoma can pursue an indolent course and that cases of CD8-positive MF may be over-represented in childhood.

Adolescent↗

Coma-induced bullae and sweat gland necrosis following clobazam.

Coma-induced bullae and sweat gland necrosis is a rare clinicopathological entity described in association with a variety of aetiopathological conditions all of which have resulted in an impairment of conscious level. We report the first case observed in association with clobazam, used as adjunctive therapy for resistant epilepsy in a 4-year old. The potential underlying mechanisms and previously reported associations are discussed.

Anti-Anxiety Agents↗

Cutaneous perineurioma: a poorly recognized tumour often misdiagnosed as epithelioid histiocytoma.

AIMS: Eleven cases of cutaneous perineurioma were studied to further characterize the histological features of this entity. METHODS AND RESULTS: The histological and immunocytochemical features of 11 cases of cutaneous perineurioma were studied and detailed by two pathologists. Clinical data were obtained from the referring clinician. Seven patients were female and four were male with ages ranging from 19 to 67 years (median 41 years). Six lesions arose on the leg. Macroscopically lesions ranged from 4 mm to 14 mm in maximum diameter (median 7 mm). Diagnostic histological features included a nonencapsulated but sharply demarcated tumour with a dumbbell architecture. The tumour cells were spindle-shaped with delicate inconspicuous cytoplasm and arranged in sheets, whorls or with a vague fascicular pattern. Epithelioid cells with moderate amounts of eosinophilic cytoplasm were frequently admixed with the spindle cells. One tumour had trabeculae of cells embedded within a dense collagenous stroma as described in sclerosing perineurioma. One case displayed a prominent myxoid stroma. Three further cases contained small foci of fibrosis or myxoid change suggesting a morphological spectrum exists in cutaneous perineurioma. Mitoses were exceptionally rare and necrosis and significant cytonuclear pleomorphism was not found. All tumours were epithelial membrane antigen (EMA) positive. Six cases showed focal positivity for factor XIIIa. Follow-up ranged from 5 months to 6 years (median 1 years). No tumour recurred or metastasized. CONCLUSIONS: The histological appearance of this tumour is broader than hitherto realized. Several cases in this series were misdiagnosed histologically and cutaneous perineuriomas may be more common than currently appreciated.

Adult↗

Malignant eccrine spiradenoma (spiradenocarcinoma): a clinicopathologic study of 12 cases.

Malignant eccrine spiradenoma is a very rare tumor. The clinicopathologic features of 12 cases are reported herein. Six patients were men, six were women, and the average patient age was 62 years. Seven tumors were located on the trunk, three on the extremities, and two in the head and neck region. All tumors were large (average size-7.5 cm). Lesions had been present from 7 months to 30 years before surgical removal. In all cases, continuity between benign eccrine spiradenoma and areas with malignant change was observed. Malignancy was evidenced by increased mitotic rate, necrosis, nuclear atypia, pleomorphism, and hyperchromasia, loss of nested and trabecular growth patterns, and absence of a dual cell population. In most cases (8 of 12), the malignant component comprised the bulk of the lesion. Two distinctive histologic patterns were observed. Five of 12 tumors exhibited abrupt transition between a benign eccrine spiradenoma and a high-grade carcinoma component. The others lacked a clear-cut transition between benign and malignant components and were diagnostically challenging. Diagnosis in such cases was established based on the loss of two cell populations, increased nuclear to cytoplasmic ratio, hyperchromasia, and marked mitotic activity. Two tumors showed focal squamous differentiation. Five of seven patients on whom there was follow-up information were free of disease (average duration of follow-up = 3.4 years). One patient developed metastases to local lymph nodes 5 years after the primary tumor was resected. This patient had no evidence of disease 16 months after resection of her lymph node metastases.

Adenocarcinoma↗

Composite hemangioendothelioma: a complex, low-grade vascular lesion mimicking angiosarcoma.

Eight cases of a previously uncharacterized vascular neoplasm, showing varying combinations of benign, low-grade malignant, and malignant vascular components are described. Seven tumors occurred in the dermis and/or subcutis and one occurred in the oral submucosa. The patients were all adults with a median age of 39.5 years (range, 21-71 years). Five patients were men. The tumors arose predominantly in the hands and feet, and the lesions were usually of several years duration. The tumors were composed of a complex admixture of histologic components that varied from tumor to tumor, such that no two tumors looked precisely the same. This was due to variation in the proportions of each component as well as the manner in which each component was distributed throughout each lesion. The predominant histologic components were epithelioid hemangioendothelioma (HE) and retiform HE, which were each present in seven of the tumors. Areas of spindle cell HE were identified in four lesions. Angiosarcoma-like elements were identified in seven tumors. One of the tumors was associated with an arteriovenous malformation and one was associated with an area of lymphangioma circumscriptum. Of six cases with follow up (median duration, 6.5 years), three have recurred locally and, to date, only one has metastasized. We think composite HE is best regarded as a low-grade malignant vascular neoplasm, and the available data suggest that it behaves more favorably than conventional angiosarcoma. The existence of these composite lesions has led to careful reexamination of the concept of HE. The term HE, in that it is currently synonymous with a low-grade malignant vascular tumor, should be reserved for lesions that have true metastatic potential, albeit with low frequency.

Adult↗

ACP best practice no 162. The histological reporting of melanoma. Association of Clinical Pathologists.

The incidence of malignant melanoma has increased steadily over the past 30 years and this type of malignancy is the leading cause of death from cutaneous malignant disease. Cutaneous malignancies, including melanoma, can be detected at a very early stage and a cure is possible with prompt detection and treatment. In recent years, and mainly because of increased awareness of the early detection of melanoma, histopathologists have been exposed more and more to melanocytic lesions. Therefore, it is essential that histopathologists are able to provide a report to the clinician that conveys relevant information in a concise and precise manner. This paper provides a set of guidelines aimed at helping histopathologists with the gross and microscopic description and diagnosis of malignant melanoma.

Humans↗

Spitz tumors in children: a grading system for risk stratification.

OBJECTIVE: To describe a grading system for risk stratification of atypical Spitz tumors in children and adolescents. In some circumstances, unequivocal distinction between Spitz nevus and melanoma is practically impossible. It is likely that these lesions for which we lack specific diagnostic criteria represent a broad histological continuum extending from benign to malignant tumors. Therefore, we propose that Spitz tumors be categorized into low-, intermediate-, or high-risk categories based on the accumulation of abnormal features. DESIGN: Retrospective study. SETTINGS: Institutional practice. PATIENTS: We present 30 cases of atypical Spitz tumors in patients younger than 18 years evaluated for at least 3 years or in whom a metastatic event developed during this period. INTERVENTION: None. MAIN OUTCOME MEASURE: The grading system was formulated after data collection. RESULTS: Among the parameters studied, only diagnosis at age greater than 10 years, diameter of the lesion greater than 10 mm, presence of ulceration, involvement of the subcutaneous fat (level V), and mitotic activity of at least 6/mm2 carried a likelihood ratio greater than 1.50 and were therefore used for the grading system. CONCLUSION: The application of an objective grading system, such as the one described herein for the first time, is the first step in providing useful information for the management of atypical Spitz tumors.

Adolescent↗

B-cell lymphoma associated with chronic lymphatic leukaemia: two cases with contrasting aggressive and indolent behaviour.

The term Richter's syndrome is used to describe the transformation of chronic lymphatic leukaemia (CLL) into a high-grade systemic lymphoma and is associated with a poor prognosis. We have undertaken detailed molecular studies in two patients with cutaneous B-cell lymphoma (CBCL) and CLL. Patient 1 exhibited a low-grade CBCL with different immunoglobulin gene rearrangements in blood and skin. By contrast, patient 2 showed identical gene rearrangements, confirmed by gene sequencing, and died within 4 months of presentation. The latter patient fulfilled the criteria for a diagnosis of cutaneous Richter's syndrome, whereas the former patient demonstrated the coincidence of CLL with a primary CBCL. Our results highlight the importance of gene rearrangement studies with sequencing for the accurate diagnosis of cutaneous Richter's syndrome.

Aged↗

Myxoid dermatofibroma.

AIMS: This report presents seven cases of a rare variant of dermatofibroma, characterized by marked mucinous stromal changes. METHODS AND RESULTS: In this retrospective clinicopathological study, lesions preferentially occurred on the lower extremities of young to middle-aged females. Clinical (differential) diagnoses included: dermatofibroma (two cases), cyst, tophus, ganglion and neurofibroma. Histology revealed well circumscribed, faintly stained dermal to subcutaneous lesions which contained abundant stromal mucin. A variable amount of spindle-shaped cells, occasional lymphocytes and fine collagen fibres were also seen. Epidermal hyperplasia above as well as storiform arrangement of spindle cells and some sclerotic collagen at the periphery of the lesion indicated the fibrohistiocytic origin. Individual histopathological features included: bizarre giant cells, perifollicular arrangement and seas of mucin with pseudovascular clefts in one case each. Immunohistochemically, all lesions were positive for KiM1p (> 50% of the cells). Moreover, two lesions showed moderate reactivity for factor XIIIa (10-25%), one each with NK1C3 (> 90%) and smooth muscle actin (50%), but were otherwise negative with a broad panel of markers. Electron microscopy in one case revealed large pools of mucin interspersed by a moderate number of fibrocytes with fine fibrillary collagen. CONCLUSION: This series confirms myxoid dermatofibroma as a rare variant of fibrohistiocytic tissue response; our series also indicates that many of these lesions might be misinterpreted as cutaneous myxoma.

Adult↗

Hobnail hemangioma: a pseudomalignant vascular lesion with a reappraisal of targetoid hemosiderotic hemangioma.

The clinicopathologic features of 15 cutanous hemangiomas having a distinctive and frequently pseudomalignant morphologic appearance are presented. There were 5 male and 9 female patients, whose ages at diagnosis ranged from 11 to 58 years (median 30.5). An angiomatous/pigmented, nontargetoid, flat, or exophytic lesion of variable duration was the main presenting sign. The tumor sizes ranged from 0.4 cm to 2 cm (median 1 cm). The locations included the lower limb, particularly the thigh (8); the trunk, including the shoulder area (4); the head (1); the gingiva (1); and the tongue (1). One patient had two lesions; none had a concomitant vascular anomaly or was suspected to have HIV infection. Treatment consisted of excisional biopsy in all cases. Follow-up information on 10 patients (range 4-66 months; median 13 months) showed no recurrence. On microscopic examination, the lesion showed a biphasic pattern characterized by the presence of well-formed, dilated, vascular channels in superficial dermis and a collagen-dissecting, pseudoangiosarcomatous pattern as the lesion infiltrated deeper into the dermis. The lining endothelium consistently showed distinctive hobnail cytomorphology; although there were endoluminal stromal papillae, there was no endothelial multilayering or tufting. Cytologic atypia was minimal or absent, and there were no mitoses. In 3 cases, the morphologic features were reminiscent of retiform hemangioendothelioma. Immunohistochemistry performed in 8 cases showed variable reactivity of endothelial cells with CD31, CD34, Factor VIII-related antigen, and Ulex europaeus agglutinin-1 in all cases; smooth muscle actin-positive pericytes were observed focally around some of the abnormal vascular spaces. The above-described hemangiomatous lesions share many features with so-called targetoid hemosiderotic hemangioma (a clinically descriptive term), but show a variable, often minimal, amount of hemosiderin deposition. The histologically descriptive term hobnail hemangioma is proposed to designate these lesions. Hobnail hemangioma should be distinguished from well-differentiated angiosarcoma, patch-stage Kaposi's sarcoma, and retiform hemangioendothelioma, with which it may be confused.

Adolescent↗

Superficial angiomyxoma: clinicopathologic analysis of a series of distinctive but poorly recognized cutaneous tumors with tendency for recurrence.

Despite being first described in 1988, superficial angiomyxoma is still a poorly recognized cutaneous tumor. Although its histologic features are distinctive, its existence seems not to be widely accepted. We analyzed the clinicopathologic and immunohistochemical features in a series of 39 cases. Twenty-five patients were males; age range was birth to 82 years (median, 45.5 years). Most cases presented as cutaneous papules, nodules, or polypoid lesions. Seventeen tumors arose on the trunk, 14 on the head and neck, and seven on the lower limbs. All cases were treated by local excision, and eight recurred locally. In four of the latter cases, there were two recurrences. Histologically, the lesions were dermal with variable involvement of the subcutis. Tumors were poorly circumscribed, but a focal lobular outline was always identified. Distinctive histologic features included extensive myxoid stroma, numerous small blood vessels, varying cellularity, acellular mucin pools, stellate or bipolar fibroblastic cells, muciphages, a sparse, mixed inflammatory cell infiltrate with notable neutrophils, and occasional plumper cells with eosinophilic cytoplasm. Cytologic atypia was mild at most, and mitotic figures were rare. In approximately 20% of cases, the primary lesion or its recurrence contained epithelial structures, including epidermoid cysts, thin strands of squamous epithelium, and small buds of basaloid cells. Immunohistochemically, tumor cells were negative for S-100 protein, smooth muscle actin, and pan-keratin. We support the concept of superficial angiomyxoma as a distinctive clinicopathologic entity that should be included in the differential diagnosis of other myxoid cutaneous tumors, including dermal nerve sheath myxoma, trichodiscoma and trichofolliculoma, and low-grade myxofibrosarcoma.

Adolescent↗

Langerhans cell histiocytosis in the elderly: a report of three cases.

Langerhans cell histiocytosis is most common in children and is unusual in the elderly. We describe 3 cases of langerhans cell histiocytosis limited to the skin in elderly patients. Biopsy specimens showed a dermal infiltrate abutting the epidermis composed of atypical langerhans cells with abundant eosinophilic cytoplasm and a "kidney-shaped" nucleus. Immunoperoxidase stain CD1a was positive in all 3 cases and S-100 stain was positive in 2. Electron microscopy revealed Birbeck granules in the cytoplasm of the atypical langerhans cells in 2 cases. Langerhans cell histiocytosis with skin involvement has a chronic course with an overall good prognosis. However, cutaneous manifestations may precede systemic involvement by many years.

Adult↗

Primary malignant melanoma with rhabdoid features: a histologic and immunocytochemical study of three cases.

Malignant rhabdoid tumors are morphologically characterized by the presence of sheets of large polygonal cells with abundant cytoplasm containing eosinophilic inclusions. They have vesicular nuclei, often with prominent central nucleoli. The term rhabdoid tumor was originally coined to describe a group of rare, aggressive renal neoplasms of childhood. Since then, similar lesions, so-called extrarenal malignant rhabdoid tumors have been increasingly reported. The evidence to date suggests that, at least in extrarenal locations, rhabdoid tumors do not constitute a homogeneous entity, but rather represent the shared morphological pattern of a diverse range of malignant neoplasms. Although such rhabdoid features are not uncommon in metastatic malignant melanoma, they have only once been briefly described in a primary lesion. We report three further cases of cutaneous primary malignant melanoma with rhabdoid morphology.

Adult↗

The effect of melanin bleaching on immunohistochemical staining in heavily pigmented melanocytic neoplasms.

The accumulation of excessive amounts of melanin in melanocytic lesions can obscure cellular morphology and can further hinder immunocytochemical procedures. We have used a modification of the potassium permanganate/oxalic acid melanin-bleaching technique, involving much reduced bleaching times, in order to remove melanin granules prior to incubation with primary antibody. We have assessed a panel of antibodies applicable to the evaluation of melanocytic lesions and in addition have also assessed antibodies that may be more useful in research. The study attempts to determine which antigens may be affected by bleaching and which are not. Antigens S100, HMB 45, NKIC3, CD34, and L26 are relatively unaffected by this procedure. Factor-VIII-related antigen and vimentin and CD68 antigens produced enhanced staining. In contrast, antigens CD3, CD31, and CD45RO were abolished. In addition, smooth muscle actin and desmin antigens demonstrated considerable nonspecific background staining and were not reliable in this study. This technique demonstrates that a fairly wide range of antigens are preserved after bleaching and that distinction between melanocytes and melanophages can reliably be performed using the conventional immunocytochemical chromogen 3,3-diaminobenzidine and without the need for elaborate counterstaining.

Actins↗

Cutaneous pilar leiomyoma: clinicopathologic analysis of 53 lesions in 45 patients.

As cutaneous pilar leiomyomas have received little attention in the recent literature, 53 lesions from 45 patients were studied to analyze their clinicopathologic features. There was an equal distribution between both sexes; most patients were adults with a wide age distribution. Both multiple (29 lesions from 21 patients) and solitary tumors (18 patients) were included. Lesions on the extremity (29 tumors) were common in both groups, whereas truncal tumors (11) were confined largely to patients with multiple lesions. In six patients the number of lesions was not specified. The tumors were painful in 17 patients. Three patients had a positive family history of similar lesions. Histologic study revealed ill-defined bundles of well-differentiated smooth muscle cells in the reticular dermis in all cases, although nine lesions had a more nodular pattern. Overlying epidermal hyperplasia was noted in 29 cases (54.7%). Immunohistochemically there appeared to be an increased number of nerve fibers within and surrounding the tumors. Mitotic activity was observed in 15 lesions (28.3%), 13 of which had <1 mitosis per 10 high power fields (HPF); the remaining two lesions had 1-2 mitoses per 10 HPF. Follow-up was available in 10 of these mitotically active tumors and ranged from 9 months to 7 years. There was no recurrence in any of them. We have concluded tentatively that leiomyomas of arrector pili origin may exhibit a low mitotic activity of <1 per 10 HPF and that this does not adversely affect the prognosis for these patients.

Adolescent↗

Mixed tumors and myoepitheliomas of soft tissue: a clinicopathologic study of 19 cases with a unifying concept.

We report 19 unusual cases of mixed tumors and myoepitheliomas arising in soft tissues. The neoplasms occurred in 12 males and seven females. The age at diagnosis ranged from 2 to 83 years (mean 35, median 30). Eight tumors arose in the upper limb, six in the lower limb, three in the trunk, and two in the head and neck region. Three cases involved both dermis and subcutis; the remainder arose in subcutaneous (13 cases) or deep subfascial soft tissue (three cases). The most common presenting complaint was a painless swelling, with duration ranging from 2 weeks to 1 year (median 2.5 months). Microscopically, the tumors were predominantly well circumscribed and lobulated. Six cases showed a focally infiltrative margin. Cardinal morphologic features included nests, cords, and ductules of epithelioid cells and/or nests of spindled cells within a hyalinized to chondromyxoid stroma. One tumor was predominantly composed of myoepithelial cells and devoid of epithelial differentiation (i.e., ductules). Cytoplasmic hyaline inclusions were noted in two cases; squamous differentiation was seen in one case. Osteoid production and/or metaplastic bone was observed in three tumors. Chondroid differentiation (usually mature) was seen in four cases. Adipocytic differentiation was seen in two tumors. Mitotic activity was variable but generally scant; atypical mitotic figures were not identified. By immunohistochemistry, 16 of 16 cases expressed pan-keratin; 16 of 17 S-100 protein; six of 14 alpha smooth muscle actin (IA4); two of 10 muscle specific actin (HHF-35); two of 10 desmin; three of 11 glial fibrillary acidic protein; and three of 16 epithelial membrane antigen. Clinical follow-up was available in 10 patients and ranged from 6 months to 20 years (mean 4.25 years, median 2 years). Two patients developed local recurrence; metastasis to lung and lymph nodes were observed in two additional patients. Both of the latter patients died. We believe that these findings expand the concept of cutaneous mixed tumors to include neoplasms composed predominantly of myoepithelial cells and to include tumors arising in deeper subcutaneous and/or subfascial tissues. The clinical behavior of such neoplasms, when arising in soft tissues, may be difficult to predict but is most often benign; however, a minority of lesions metastasize. Until larger studies with longer follow-up are available, treatment and prognostication are probably best based on criteria used in comparable salivary gland tumors.

Adult↗