T1799A BRAF mutation is common in PUVA lentigines.
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Humans↗
Biomedical subjects
Steven Kaddu
Publications and source records attributed to Steven Kaddu.
Teledermatopathology: a controlled study about diagnostic validity and technical requirements for digital transmission.
Telepathology is the practice of diagnostic histopathology performed on digital pictures. In this study, we focused on the technical requirements for achievement of a correct diagnosis on digital histopathologic images. A collection of 560 melanocytic lesions was selected from the files of the Department of Dermatology, Medical University of Graz, Austria. From each lesion one histologic slide was completely digitally scanned with a robotic microscope. Digital pictures were reviewed by 4 dermatopathologists using a presentation program, which recorded the number of image calls, applied magnifications, overall time needed, and amount of transmitted bits during the digital sign-out. One month later, the 4 microscopists had to review the corresponding slides and render a direct diagnosis on each case. Telepathologic diagnoses corresponded with the original diagnoses in a range from 90.4% to 96.4% of cases (kappa 0.80 to 0.93; P < 0.001). The median time needed for achievement of a diagnosis was 22 seconds and was significantly higher for melanomas compared with nevi. The median transmission effort for each diagnosis was 510 kilobytes after JPEG compression. Using an ISDN line with a transmission capacity of 64 kilobits/ second, this correlates to a transmission time of about 1 minute. Our results demonstrate that correct reporting on digital histopathologic images is possible with only a little time exposure. For an adequately fast transmission ISDN lines are suffcient after JPEG compression.
Dermatology↗
Cutaneous myoepithelial neoplasms: clinicopathologic and immunohistochemical study of 20 cases suggesting a continuous spectrum ranging from benign mixed tumor of the skin to cutaneous myoepithelioma and myoepithelial carcinoma.
BACKGROUND: Myoepithelial neoplasms, both benign and malignant, are rare but well-established clinicopathologic entities in the salivary glands, the breast, and the lung. Despite similarities between cutaneous sweat glands and glandular structures in the above-mentioned organs as well as the presence of regular myoepithelial cells around cutaneous eccrine/apocrine glands, the concept of cutaneous myoepithelial neoplasms is still debatable and not commonly accepted. METHODS: Twenty cutaneous myoepithelial neoplasms have been studied histologically and immunohistochemically. RESULTS: Nine neoplasms showed features of benign mixed tumor of the skin (chondroid syringoma) (five females and four males, age range 19-65 years, all cases arose in the head and neck region). Two cases represented the eccrine and seven the apocrine subtype. Interestingly, in three cases of the apocrine subtype, solid areas composed predominantly of myoepithelial cells were detected; these neoplasms were designated as benign mixed tumors with prominent myoepithelial cells. Nine cutaneous neoplasms were composed of spindled, epithelioid, and plasmocytoid cells without ductal differentiation and immunohistochemically stained variably positive for vimentin, epithelial and myogenic markers, S-100 protein, calponin, and glial fibrillary acidic protein (four females and five males, age range 3-71 years, four cases arose in the head and neck region and one case each on the finger, the thigh, the lower leg, the foot, and the breast, respectively); these neoplasms were designated as cutaneous myoepitheliomas. Two morphologically malignant neoplasms with cytologic and immunohistochemical features of myoepithelial cells arose on the face of a 70-year-old female and a 79-year-old male patient; these neoplasms were designated as malignant cutaneous myoepitheliomas (cutaneous myoepithelial carcinomas). CONCLUSIONS: The study suggests a continuous spectrum of cutaneous myoepithelial neoplasms ranging from benign mixed tumor of the skin to cutaneous myoepithelioma and cutaneous myoepithelial carcinoma. Further studies with extended follow-up information are necessary to establish prognostic factors.
Adolescent↗
Loss of expression of tuberin and hamartin in tuberous sclerosis complex-associated but not in sporadic angiofibromas.
BACKGROUND: Angiofibromas occur sporadically, and they develop in most patients with tuberous sclerosis complex (TSC), which is associated with alterations of the tumor suppressor genes TSC1 or TSC2. Loss of tuberin, the protein product of TSC2, has been shown in the interstitial fibroblast compartment of TSC-associated angiofibromas. It is unclear whether there is also a loss of hamartin, the product of TSC1 in TSC-associated and sporadic angiofibromas. METHODS: The expression of hamartin and tuberin was analyzed by immunohistochemistry in 59 TSC-associated and 12 sporadic angiofibromas using affinity-purified antibodies. RESULTS: Loss of expression of both tuberin and hamartin was detected in 14 angiofibromas, loss of only tuberin in three, and loss of only hamartin in four TSC-associated angiofibromas; but there was no loss in the sporadic angiofibromas. Only the interstitial cells, but not the vascular cells, showed a loss of expression of tuberin or hamartin. CONCLUSIONS: Loss of tuberin or hamartin occurred in a minority of the TSC-linked angiofibromas, but not in the sporadic angiofibromas. The absence of both tuberin and hamartin in some of the tumors suggests that the stability of tuberin and hamartin, which are believed to form an active complex in vivo, is negatively affected by the absence of either of the partners.
Angiofibroma↗
A distinctive type of widespread congenital melanocytic nevus with large nodules.
We report an unusual case of congenital melanocytic nevus presenting in a 19-year-old African woman as widespread papules and variably sized nodules and tumors affecting the entire body, including the palms, soles, and oral mucous membrane. Histopathologic examination of 3 representative skin lesions showed mainly dermal aggregations of round to oval, focally pigmented, monomorphous melanocytes, arranged in nodular and plexiform patterns. Scattered areas with spindle-shaped dendritic melanocytes surrounded by fibrosis were also noted in the center of the lesions. The clinical and histopathologic findings were similar to those in 2 other previously reported cases, except that in 1 of the earlier cases the skin nodules were composed of spindle-shaped cells, suggesting a type of blue nevus. The findings in our case indicate a broader spectrum of morphologic features in this condition, with dermal aggregations of melanocytes showing congenital features, representing a common histopathologic denominator. Based on this observation, we suggest the term "widespread congenital dermal nevus with large nodules" to be the most appropriate for this rare, but distinctive, type of congenital nevus.
Adult↗
Dermoscopic and histopathologic diagnosis of equivocal melanocytic skin lesions: an interdisciplinary study on 107 cases.
BACKGROUND: Dermoscopy (dermatoscopy, epiluminescence microscopy) is increasingly employed for the preoperative detection of cutaneous melanoma; dermoscopic features of pigmented skin lesions have been previously defined using histopathology as the key to the code. In a preliminary study on 10 cases evaluated by nine dermoscopists and nine histopathologists, the authors experienced that when at least two dermoscopists disagree in evaluating a melanocytic lesion, even histopathologic consultations may give equivocal results. METHODS: One hundred seven melanocytic skin lesions, consecutively excised because of equivocal clinical and/or dermoscopic features, were retrospectively examined by eight dermoscopists and eight histopathologists; the diagnostic interobserver agreement was calculated by means of the Schouten k statistics. After histopathologic consultations, all 107 lesions underwent unblinded dermoscopic re-evaluation in order to find which dermoscopic features had given rise to histopathologic diagnostic difficulties. RESULTS: The interobserver ageement was good for both dermoscopy (k = 0.53) and histopathology (k = 0.74). Out of 48 cases evaluated by the dermoscopists in complete accordance, only 8 (16.7%) received at least one conflicting histopathologic diagnosis. Instead, among the remaining 59 cases with at least one disagreeing dermoscopic diagnosis, 21 (35.6%) received at least one disagreeing histopathologic diagnosis. The unblinded dermoscopic re-evaluation showed that five out of seven lesions with clear-cut regression structures were histopathologically controversial. CONCLUSIONS: At least for selected and reasonably difficult lesions, a diagnostic discrepancy among formally trained dermoscopists seems to be predictive for a diagnostic disagreement among histopathologists. Lesions showing clear-cut regression structures are prone to give some histopathologic disagreement.
Adolescent↗
Warty dyskeratoma--"follicular dyskeratoma": analysis of clinicopathologic features of a distinctive follicular adnexal neoplasm.
BACKGROUND: The clinicopathologic spectrum of warty dyskeratoma (WD) is not well characterized and the pathogenesis of this unusual lesion is still unclear. OBJECTIVE: We reviewed the clinical and histopathologic spectrum of WD and investigated a possible involvement of human papillomavirus (HPV) infection in onset of this lesion. METHODS: A total of 46 cases of WD were analyzed clinically and histopathologically. Polymerase chain reaction (PCR) analysis for HPV-DNA was performed in 13 lesions of WD. RESULTS: A total of 46 lesions of WD from 45 patients (M/F ratio, 1:1.8; mean age 59.8 years, median 61 years, age range 3-88 years) presented as solitary papules or small nodules on the head and neck (32 cases), trunk (9 cases), lower extremities (4 cases), and upper extremities (1 case). One patient had 2 lesions. No patient had clinical signs of Darier's or Grover's disease. Histopathologically on scanning magnification, lesions showed mainly 3 architectural patterns, namely, cup-shaped (29 cases), cystic (6 cases), and nodular (2 cases). In 9 cases, a combination of two of these morphologic patterns was observed. Characteristically, the epithelial component in all WDs displayed foci of acantholytic dyskeratosis. Variable features suggestive of follicular differentiation toward the infundibular portion of a normal hair follicle were also observed, including a focal contiguity to pilosebaceous units in most cases (63%), and the presence of small infundibular cystic structures in a subset of lesions (46%). The majority of lesions (83%) also revealed a hyalinized or fibrous stroma with intrastromal clefts. PCR analysis for HPV-DNA performed in 13 cases inclusive of all representative architectural patterns was negative. CONCLUSION: We conclude that WD shows a wider spectrum of morphologic features than previously recognized. Despite some histopathologic similarities to viral warts, WD is not a manifestation of HPV infection. On the other hand, the majority of these lesions display overall histopathologic features consistent with a follicular adnexal neoplasm. On the basis of this finding, we propose the alternative term follicular dyskeratoma to better reflect the distinctive features of this peculiar lesion.
Adolescent↗
Atypical fibrous histiocytoma of the skin: clinicopathologic analysis of 59 cases with evidence of infrequent metastasis.
Atypical fibrous histiocytoma is an uncommon, poorly documented variant of cutaneous fibrous histiocytoma. We studied 59 cases of atypical fibrous histiocytoma to better characterize the clinicopathologic spectrum. There were 33 males and 26 females (median age 38 years; range 5-79 years) with solitary lesions arising on lower (25 cases) and upper (17 cases) extremities, trunk (6 cases), head and neck (4 cases), and vulva (1 case); anatomic location was not stated in six cases. Lesions measured 0.4-8 cm in diameter (median 1.5 cm) and clinically were nodules (40 cases), polypoid tumors (18 cases), or a slightly elevated plaque (1 case). Histologically, the lesions were primarily dermal with superficial involvement of the subcutis in one third of the cases. Salient features included a proliferation of pleomorphic, plump, spindle, and/or polyhedral cells with mainly large, hyperchromatic, irregular, or bizarre nuclei, set in a background of classic features of fibrous histiocytoma, including spindle cell areas showing a storiform pattern and entrapped thickened, hyaline collagen bundles, especially at the periphery. Multinucleated giant cells, often with bizarre nuclei and foamy, sometimes hemosiderin-rich, cytoplasm were also variably present. The degree of pleomorphism varied from only focal and minimal (14 cases) or moderate (24 cases) to marked (21 cases). Mitotic activity was observed in 55 lesions, and the number of mitotic figures ranged from 1 to 15 per 10 high power fields. Atypical mitoses were noted in 20 lesions. Furthermore, some cases of atypical fibrous histiocytoma displayed other worrisome features less often observed in ordinary FH, including unusually large size (diameter >2 cm, 8 cases), involvement of the superficial subcutis (19 cases), and geographic necrosis (7 cases). Immunohistochemical studies performed in 42 cases showed only focal smooth muscle actin (10 cases) and CD34 (4 cases) positivity, whereas CD68, S-100 protein, desmin, pan-keratin, and epithelial membrane antigen were negative. Clinical follow-up data available in 21 patients (mean duration of follow-up 50.6 months, median 43 months) revealed local recurrences in three patients (one repeated); two patients developed distant metastases, one of whom died after 96 months. These two cases were not histologically distinct from the group as a whole. We conclude that atypical fibrous histiocytoma has a broader clinicopathologic spectrum than previously realized. Lesions with floridly atypical features represent potential pitfalls for overinterpretation as pleomorphic sarcoma, which would appear to be inappropriate in most cases. Provided that atypical fibrous histiocytoma is treated by complete excision, a benign outcome is to be expected in most cases. However, similar to the cellular and aneurysmal variants of fibrous histiocytoma, atypical fibrous histiocytoma shows a higher tendency to recur locally than ordinary fibrous histiocytoma and may rarely metastasize.
Adolescent↗