Distinct pathways in the pathogenesis of sebaceous carcinomas implicated by differentially expressed microRNAs.

IMPORTANCE: The molecular-genetic alterations contributing to the pathogenesis of sebaceous carcinoma and sebaceous adenoma remain poorly understood. Given that sebaceous carcinoma is associated with substantial morbidity and mortality, there is a critical need to delineate the pathways driving sebaceous carcinoma and candidate molecules for targeted therapy. OBJECTIVE: To describe differentially expressed microRNAs (miRNAs) in a series of periocular sebaceous carcinomas compared with sebaceous adenomas in order to identify pathways driving the pathogenesis of sebaceous carcinoma. DESIGN, SETTING, AND PARTICIPANTS: Thirty sebaceous carcinomas and 23 sebaceous adenomas (including 11 that were confirmed to be related to Muir-Torre syndrome and 6 that were confirmed to be sporadic) were obtained from archives (from 48 patients) of 2 institutions (University of Texas MD Anderson Cancer Center, Houston, and Siriraj Hospital, Mahidol University, Bangkok, Thailand) and profiled. MAIN OUTCOMES AND MEASURES: Expression of miRNAs was determined using total RNA from formalin-fixed, paraffin-embedded tissue and real-time reverse transcription-polymerase chain reaction performed in a microfluidics card containing 378 unique miRNAs. Fold change was determined using the ΔΔCt method (reference probe, RNU48). Median centering was used to normalize the data. Two-sample t tests were used to identify differentially expressed miRNAs. The false discovery rate was assessed by ß-uniform mixture analysis of P values from the t statistics. Significance was defined by this estimated false discovery rate. RESULTS: Serial testing and validation confirmed overexpression of 2 miRNAs previously reported to be oncogenic, miR-486-5p (4.4-fold; P = 2.4 × 10-8) and miR-184 (3.5-fold; P = 1.7 × 10-6), in sebaceous carcinoma compared with sebaceous adenoma and downregulation of 2 miRNAs previously reported to have tumor-suppressive properties, miR-211 (-5.8-fold; P = 2.3 × 10-9) and miR-518d (-4.5-fold; 6.7 × 10-5), in sebaceous carcinoma compared with sebaceous adenoma. CONCLUSIONS AND RELEVANCE: Sebaceous carcinoma exhibits an miRNA expression profile distinct from that of sebaceous adenoma, implicating dysregulation of NF-κB and PTEN (targets of miR-486-5p) and TGF-ß signaling (target of miR-211) in the pathogenesis of sebaceous carcinoma. The identification of miRNAs whose expression is altered in sebaceous carcinoma compared with sebaceous adenoma provides a novel entry point for a more comprehensive understanding of the molecular-genetic alterations pivotal to the development of sebaceous carcinoma.

Melanocytic matricoma: two cases of a rare entity in women.

Melanocytic matricoma is a rare cutaneous adnexal tumor occurring in humans with only 13 cases reported in the literature. The typical lesion is a circumscribed pigmented nodule on sun-damaged skin. Most cases have occurred in elderly men. The tumor contains a mixed population of matrical cells, supramatrical cells, shadow or ghost cells, and dendritic melanocytes. We report two cases of melanocytic matricoma in two elderly women with unusual histopathological features such as cystic degeneration and focal granulomatous inflammation, which are considered to be atypical for this entity.

Hair follicle counts in Thai population: a study on the vertex scalp area.

OBJECTIVE: To assess the normal value of the hair follicle counts in a 4-mm punch biopsy on the vertex scalp area from the Thai population. To compare the hair follicle count in the present study with those in previous described reports. MATERIAL AND METHOD: Twenty autopsy patients of clinically normal scalp were obtained for study from the Department of Forensic Medicine, Siriraj Hospital, Mahidol University. A 4-mm punch biopsy was performed on each patient on the vertex area of the scalp and, subsequently, horizontally bisected at the level of 1 mm below the skin surface and studied by hematoxylin-eosin staining. The total number of hair follicles, the phase of each hair follicle in a normal hair cycle, the number of terminal hairs, intermediate hairs, vellus hairs, and hair follicular unit were also included in this study and compared to those in previously described reports. RESULTS: Of our 20 studied cases, the mean numbers of total hair follicle counts, terminal, intermediate, and vellus hair follicles were 28.3 +/- 9.2, 16.5 +/- 8.4, 5.0 +/- 4.6, and 6.9 +/- 7.0 respectively. The density of hair follicles in our study was statistically less than those found in Caucasians (p-value = 0.002) but more than those in African-Americans (p-value = 0.004) and in Koreans (p-value < 0.001). CONCLUSION: Data collected from previous publications provided only the number of hair follicles in other ethnic groups, but not from the Thai population. The number of hair follicles described in those studies may be unreliable and invalid in the interpretation of scalp biopsies in alopecia Thai patients. They may lead to a misdiagnosis of the disease. The density of hair follicles in Caucasians, African-Americans, Koreans, and Thai population were authentically different according to their ethnic backgrounds. This is important because the number of hair follicles should be considered when a pathologist evaluates the scalp biopsy specimens of alopecia patients.

A 7-Year History of Necrobiotic Xanthogranuloma following Asymptomatic Multiple Myeloma: A Case Report.

Necrobiotic xanthogranuloma (NXG) is a rare destructive xanthomatous granuloma with chronic, indolent, and progressive course. The morbidity and mortality are the results from wound complications and associated disorders. Because of its strong association with monoclonal gammopathy and multiple myeloma, early recognition of disease is mandatory to monitor and prevent systemic involvements of hematologic malignancies.

Cutaneous lymphoepithelioma-like carcinoma: report of three cases.

BACKGROUND: Cutaneous lymphoepithelioma-like carcinoma (cutaneous LELC) is an extremely rare malignant neoplasm with unclear histogenesis. Its histopathologic features are like those of lymphoepithelioma-like carcinoma occurring in the nasopharynx and in visceral organs especially salivary glands. MATERIAL AND METHOD: The authors reported on one male and two female patients of cutaneous LELC with immunohistochemical and electron microscopic study. All patients were of old age. All cutaneous LELCs in this report occurred on the patient's face, one of each on the eyelid, conjunctiva, and cheek. RESULTS: All resection specimens showed the typical histopathologic features of those of LELC, i.e. well-defined tumor lobules mainly located in the dermis and extending into the panniculus. These tumor lobules typically displayed ill-defined clusters/nests of large epitheloid cells with pale eosinophilic cytoplasm, atypical vesicular nuclei possessing prominent nucleoli and were surrounded by dense lymphoplasmacytic infiltration. Immunocytohistochemically, these epitheloid cells showed epithelial differentiation by the expression of epithelial membrane antigen (EMA), P63, CK5/6 and CAM5.2 but were negative to CK20, CEA and Ebstein-Barr virus (EBV). Squamous cell differentiation by the presence of desmosomes by electron microscopic study was also noted in two patients (case 1 and 3). CONCLUSION: The findings described above indicated that cutaneous LELC was a malignant neoplasm exhibiting squamous cell differentiation.

Sebaceous neoplasms in Siriraj Hospital, Mahidol University: a 9-year-retrospective study.

BACKGROUND: Sebaceous neoplasms are adnexal neoplasms that contain a varying number ofsebocytes, i.e. large cells with lipid-laden vacuolated cytoplasm, soap-bubble in appearance, and crenate nuclei. They are uncommon compared to other adnexal neoplasms. Various sebaceous neoplasms with complex histopathologic features and varying degree ofsebaceous cells differentiation have been described in the literature. OBJECTIVES: To study the prevalence of sebaceous neoplasms, i.e., nevus sebaceus, sebaceous hyperplasia, sebaceous adenoma, sebaceoma, sebaceous epithelioma, superficial epithelioma with sebaceous differentiation, and sebaceous carcinoma diagnosed in the Department of Pathology, Siriraj Hospital, Mahidol University during the 9-year-period between 1997 and 2005. To study the prevalence of tumor transformation that occurs in nevus sebaceus. MATERIAL AND METHOD: A retrospective study of all sebaceous neoplasms including Nevus sebaceous, sebaceous hyperplasia, sebaceous adenoma, sebaceoma, sebaceous epithelioma, superficial epithelioma with sebaceous differentiation, sebaceous carcinoma, and all neoplasms containing the term "sebaceous" was performed. All slides were re-analyzed and re-diagnosed, without knowledge of the previous diagnosis or any clinical data, according to the criteria described in the standard textbooks of dermatopathology by Elder, McKee. Comparison between the previous diagnoses and the reviewed diagnoses was performed to assess the initial accuracy of all sebaceous neoplasms diagnosed. Small-sized biopsies or biopsies that possess incomplete sebaceous differentiation, in which the sebocytes were few and subtle, sometimes are difFicult to diagnose. In these instances, the clinical correlation was needed for positive diagnosis. Afterwards, these reviewed diagnoses were recorded and classified according to the patient's age, gender, and localization. RESULTS: Two hundred seven sebaceous neoplasms (2.34%) from the 8819 skin biopsies that were taken in the Department of Pathology, Siriraj Hospital during the 9-year-period, were included After exclusion of some authentically non-sebaceous neoplasms, 182 sebaceous neoplasms were found Nevus sebaceus (n=85, 46.7%) and sebaceous hyperplasia (n=64, 35.1%) were the two most common benign lesions. The others were sebaceoma (n=3, 1.6%), sebaceous adenoma (n=2, 1.1%), sebaceous epithelioma (n=1, 0.5%), sebaceous carcinoma (n=26, 14.3%), and one unclassified sebaceous lesion that could not be considered a neoplasm. Tumor degeneration was found in 14 nevus sebaceus in which 21 neoplasms existed, namely, trichilemmoma (wart)-like lesion (n=4), primitive follicular induction (n=7), syringocystadenoma papilliferum (n=3), trichoblastoma (n=3), and one of each of trichoepithelioma, sebaceous adenoma, tumor of follicular infundiculum, and mucoepidermoid carcinoma. CONCLUSION: Twenty-six sebaceous carcinomas out of 182 sebaceous neoplasms, occurring mostly on the patients'eyelids, were found The most common sebaceous neoplasm was nevus sebaceus (n=85); the prophylactic excision of this lesion was recommended as tumor degeneration was frequent (14 out of 85 cases). Epithelial membrane antigen (EMA) usually decorated both normal and abnormal sebocytes. It was very helpful in the detection of sebocytes in basaloid cells in sebaceous neoplasms and among lymphoid cells within metastasized lymph nodes and a discriminant between sebaceous and nonsebaceous neoplasms.

Mucoepidermoid (adenosquamous) carcinoma, trichoblastoma, trichilemmoma, sebaceous adenoma, tumor of follicular infundibulum and syringocystadenoma papilliferum arising within 2 persistent lesions of nevus sebaceous: report of a case.

Nevus sebaceous of Jadassohn (SNJ) is a congenital, hamartoma of multiple skin structures and may classically evolve through several stages of maturation. Many neoplasms have been reported to arise in association with SNJ, most commonly trichoblastoma and syringocystadenoma papilliferum. The coexistence of 3 or more tumors arising simultaneously within 1 lesion of SNJ is very rare. We report a case of a 66-year-old woman with a coexistence of trichoblastoma, trichilemmoma, sebaceous adenoma, tumor of follicular infundibulum, syringocystadenoma papilliferum, and mucoepidermoid or adenosquamous carcinoma arising in 2 separate and persistent SNJ exhibiting on her face with subsequent parotid node metastasis. This report illustrates an extraordinary case of adnexal neoplasms displaying diverse lines of differentiation arising within lesions of SNJ. We also reported the second instance of mucoepidermoid arising within the lesion of SNJ and also added sebaceous adenoma to the list of sebaceous tumors arising within this lesion. Prophylactic excision or at least close clinical surveillance for sudden development of new growths is warranted.

Severe congenital systemic juvenile xanthogranuloma in monozygotic twins.

Juvenile xanthogranuloma, a histiocyte disorder, usually presents with a solitary cutaneous lesion. Juvenile xanthogranuloma with extracutaneous involvement is a rare disease in which significant morbidity and occasional deaths may occur. Monozygotic twins with congenital systemic juvenile xanthogranuloma who presented with multiple skin lesions, hepatosplenomegaly, liver failure, and bone marrow involvement were reported. The diagnosis of systemic juvenile xanthogranuloma was confirmed by histology and immunohistochemical stains of the skin with liver biopsies revealing dense infiltration of lymphohistiocytes with typical Touton giant cells staining positive for CD68 and negative for CD1a and S-100 protein. Both of them received systemic prednisolone 1 mg/kg/day which was gradually tapered off with time according to clinical and investigative responses. At the 17-month follow-up period, both patients showed remarkable regression in all symptoms and laboratory studies.

Hematidrosis: a pathologic process or stigmata. A case report with comprehensive histopathologic and immunoperoxidase studies.

Cases of hematidrosis (bloody sweat) are extremely rare. This disease has been described in various terms and has been often tied to religious belief as stigmatization. We report a typical patient with hematidrosis in a 14-year-old girl who frequently bled from her scalp and palms, and, occasionally, from trunk, soles, and legs. The bloody sweat from her scalp contained all blood elements. Immediate biopsy after there was bleeding on her scalp showed multiple blood-filled spaces that opened directly into the follicular canals or on to the skin surface. Immunoperoxidase studies failed to demonstrate vascular nature of these spaces. Our study explained how and why there was bleeding in our patient and in patients with related conditions as described in earlier literatures. We also explained why this phenomenon was intermittent because the spaces indicated above will disappear after exuding their content but then reoccurred after the blood flow was reestablished.

Histopathologic aid to diagnosis of sarcoidosis: report of 8 cases.

Sarcoidosis is a multisystemic disease of unknown etiology. The disease is common in blacks and is very rare in Thailand. It presents as one of the most variable manifestations usually affecting the lungs and intrathoracic lymph nodes. Other organs such as liver, spleen, joints and eyes including skin are also involved The common cutaneous lesions are maculopapular, erythematous plaque, subcutaneous nodule, scar and lupus pernio. No reliable indicator is useful for diagnosis except the histopathologic change which is the only way for approaching this disease. Sarcoidosis is the disease of exclusion. Various infections producing granulomas should be excluded histologically. The ultimate diagnosis requires clinical correlation, laboratory investigations, chest X-ray as well as available tissue culture. Herein, the authors reported eight cases of sarcoidosis by retrospective study primarily diagnosed by histopathological findings at Siriraj Hospital from January, 1997 to December, 2004 with many different clinical presentations. Despite the diverse clinical pictures, interestingly, the presented patients almost had the same histopathologic findings as small, uniform, discrete naked granulomas usually without necrosis. These findings act as a hallmark for diagnosis of this disease.

Detection and identification of Mycobacterium species by polymerase chain reaction (PCR) from paraffin-embedded tissue compare to AFB staining in pathological sections.

BACKGROUND: Polymerase chain reaction (PCR) is a recent, rapid and reliable method in the detection of causative organism. The authors tried to determine the possibility of using PCR technique as an alternative way to detect mycobacterial DNA from paraffin-embedded tissue to avoid repeated biopsy from the patient. MATERIAL AND METHOD: Paraffin-embedded tissue blocks, the corresponding histopathologic slides, and cultural results were retrospectively searched for according to the patient's records, the granuloma clinic, Department of Dermatology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand from 1994-2000. One hundred and thirty-one tissue blocks and slides were found but only 120 cultural results were retrieved Histologic sections were reviewed for AFB findings and PCR was done using 16S rRNA sequences to detect M. tuberculosis by one-tube nested technique and multiplex PCR for M. marinum and M. fortuitum complex. RESULTS: The causative organisms were identified by AFB staining in pathologic sections 31.29%, by PCR 35.87%, and by culture 30.00% of tested samples. The sensitivity of PCR when compared to AFB result was 29.26%, specificity 61.11% but when compared to cultural results, the sensitivity of PCR was 66.67% and AFB sensitivity was 41.66% with specificity 76.19% and 72.61% respectively. CONCLUSION: The low sensitivity of the PCR method may be due to formalin fixation, deparaffinization process, DNA extraction method, the use of 16S rRNA-based primers and the length of the expected product, and the tissue type that may have Taq polymerase inhibitor. Therefore, PCR should be used to augment the information of the conventional method in the diagnosis of mycobacterial infection.

Mycobacterial skin infections: comparison between histopathologic features and detection of acid fast bacilli in pathologic section.

BACKGROUND: Detection of acid fast bacilli (AFB) in chronic granulomatous inflammation is an important clue for mycobacterial infection. DESIGN: A retrospective review of 104 pathologic sections (from 1994 to 2001) of suspected cases of mycobacterial (tuberculous and nontuberculous) skin infections to study histopathologic features and the correlation with the presence of AFB in the section was performed. RESULTS: All cases showed granulomatous inflammations that can be categorized into 4 types: mixed cell, suppurative, tuberculoid and palisading granuloma. AFB was found in 32 sections (30.77%). Ninety five specimens from 104 specimens were simultaneously cultured. AFB positive cases yielded higher positive cultural results, 17 from 29 cases (58.62%) compared to the AFB negative group, 23 from 66 cases, (34.85%). Mixed cell granuloma was the most common histologic feature, but suppurative granuloma was the most common histological feature (56.25%) in which AFB could be found, which was statistically significantly different from other types of granuloma. Tuberculoid granuloma was more common in the AFB negative group (20.83%) compared to the AFB positive group (9.37%) but the difference was not statistically significant. In cases that AFB could not be found, the inflammation tended to be located in the upper half of the dermis. CONCLUSION: AFB can be more frequently detected in suppurative granuloma that might be located in any portion of the dermis. This finding was not species specific.

Nontuberculous mycobacterial skin infections: clinical and bacteriological studies.

OBJECTIVE: Nontuberculous mycobacterial (NTM) skin infections were analysed in terms of clinical manifestation in different species to provide clues for the clinical diagnosis and sensitivity patterns of these species were studied for planning appropriate therapy. DESIGN: A retrospective study was performed in 123 suspected cases of NTM infections from January 1994 to December 2000. NTM infection was documented by culture result of the infected tissue obtained by skin biopsy. Drug susceptibility test was done as requested. RESULT: Rapid growers (M. fortuitum-chelonae) were found in 26 cases (65%) and M. marinum was responsible for 12 cases (30%) and caused only localized skin lesions on arms or legs as indurated plaque, Disseminated skin infections manifested as multiple abscesses were found in 2 cases caused by M. avium in an HIV-infected male patient and mixed infection of M. szulgai and M. terrae in an immunocompetent female patient after a dental procedure. Both sexes were affected equally in overall number but male predominated in M. marinum infection and females predominated in rapid growers. All ages can be affected but most cases were middle aged. Scrofuloderma-like cervical lymphadenitis and cutaneous abscesses were the common manifestation of rapid grower infections. Hyperkeratotic verrucous plaques (tuberculosis verrucosa cutis-like) and sporotrichoid lesions were the common manifestations of M. marinum infection. M. marinum is sensitive to minocyclin, clarithromycin, amikacin, rifampicin and ethambutol and a good clinical response was obtained with doxycyclin 100 mg orally twice a day for 3 months. Clarithromycin and amikacin showed in vitro activity against the same strain of M. fortuitum but most strains of rapid growers resisted antituberculous drugs and also various antibiotics. CONCLUSION: Clinical manifestations can be used as clues for diagnosis. Medical therapy is recommended for M. marinum infection and surgical treatment is recommended for rapid growers.

Scrofuloderma and Sweet's syndrome.

BACKGROUND: In recent years, the rare association of Sweet's syndrome with nontuberculous mycobacterial lymphadenitis has been reported. OBJECTIVE: To report the clinical, demographic, and bacteriologic data and association with Sweet's syndrome of 18 patients with scrofuloderma and scrofuloderma-like condition caused by nontuberculous mycobacterial infections seen during the past 7 years (1994-2000). METHODS: In all patients, a biopsy specimen was obtained for histopathologic and microbiologic studies. Patients from whom Mycobacterium tuberculosis and nontuberculous mycobacteria were isolated from the culture of skin biopsy specimens were included. Deep fungal infection was excluded by the lack of a fungal element in histologic section and cultural methods. The patients were treated with antimicrobials or antituberculous drugs according to the causative species. RESULTS: Eighteen cases of scrofuloderma (nine male, nine female; mean age, 36.9 years) were found among 104 patients with cutaneous tuberculosis and nontuberculous mycobacterial cutaneous infections. Sixteen of the 18 cases had lymphadenitis as the underlying focus of scrofuloderma: 15 cases occurred in the cervical group and one case in the inguinal area. One case drained from the soft tissue and one from the paranasal air sinus. Five cases had multiple episodes of Sweet' s syndrome during the course of treatment. Most cases in this group (four of the five) were middle-aged women with cervical lymphadenitis, and the most common species were rapid growers. CONCLUSIONS: Age, sex, and the site of infection may have some influence on the association with Sweet's syndrome in nontuberculous mycobacterial infections.