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1.
J Cutan Pathol ; 50(10): 873-877, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37519087

ABSTRACT

The 2022-2023 mpox outbreak is a global worldwide concern, especially since the virus was previously mainly localized regionally in Central and West Africa. The infection is typically self-limiting and transmitted by close contact/exposure with infected material. Recent cases have been known to present atypically without prodromal symptoms and initially with skin lesions. The histopathology of mpox lesions is rarely reported. Here, we present two middle-aged males presenting initially with painless skin lesions confirmed for mpox by nucleic acid amplification assay. Skin biopsies of the lesion were available for clinicopathologic correlation. Histopathology demonstrated ulceration with viral cytopathologic changes.


Subject(s)
Mpox (monkeypox) , Male , Middle Aged , Humans , Biopsy , Cytology
2.
J Cutan Pathol ; 49(8): 709-716, 2022 Aug.
Article in English | MEDLINE | ID: mdl-35488519

ABSTRACT

BACKGROUND: Spitzoid melanocytic neoplasms are well known to be diagnostically challenging. Immunohistochemistry (IHC) and molecular approaches have been used as ancillary diagnostic tests. Herein, we investigate the use of PRAME IHC for the assessment of spitzoid melanocytic neoplasms. METHODS: Ten Spitz nevi, 14 atypical Spitz tumors, and 11 spitzoid melanomas were retrieved, and PRAME IHC was scored on a scale of 1-4 (in % quartiles). Intensity of staining was categorized as weak or strong. Cases with no staining received a score of 0. Positive lymph nodes from three spitzoid melanomas were also analyzed. RESULTS: Spitz nevi, atypical Spitz tumors, and spitzoid melanomas had mean PRAME IHC scores of 1.20, 0.93, and 3.36, respectively. The percentage of cases with a score 3 or higher for each category of spitzoid neoplasms are as follows: Spitz nevus (20%), atypical Spitz tumor (0%), and spitzoid melanoma (82%). Among the spitzoid melanomas, three cases had positive sentinel lymph nodes, which showed PRAME score of 2, 4, and 4 in the metastatic deposits. CONCLUSIONS: Previous reports revealed PRAME IHC as useful tool to distinguish benign from malignant melanocytic lesions. The results presented here are concordant with the prior studies, but expand the application of this marker to Spitz nevi/tumors and spitzoid melanomas. The present findings suggest the potential diagnostic utility of PRAME IHC in the assessment of spitzoid melanocytic lesions, particularly in distinguishing spitzoid melanomas from Spitz nevi and atypical Spitz tumors.


Subject(s)
Melanoma , Nevus, Epithelioid and Spindle Cell , Skin Neoplasms , Antigens, Neoplasm , Diagnosis, Differential , Humans , Immunohistochemistry , Melanoma/diagnosis , Melanoma/pathology , Nevus, Epithelioid and Spindle Cell/diagnosis , Skin Neoplasms/diagnosis , Skin Neoplasms/pathology
3.
J Cutan Pathol ; 48(7): 980-985, 2021 Jul.
Article in English | MEDLINE | ID: mdl-33844324

ABSTRACT

Cellular neurothekeoma is a cutaneous tumor with a distinctive histopathologic appearance characterized by a dermal-based multinodular proliferation of epithelioid to spindled cells. Although the tumor may show varying amounts of myxoid stroma, extensive myxoid change is uncommon. The tumor typically presents as a solitary nodule with a predilection for the head and neck and upper limbs; examples of multiple cellular neurothekeomas are decidedly rare. The present report describes a unique case of multiple myxoid cellular neurothekeomas arising in a 60-year-old female with systemic lupus erythematosus. Two papular lesions were identified involving the skin inferior to the umbilicus and the left inguinal crease. Both lesions were histopathologically similar, forming a nodular mass composed of epithelioid cells in a prominent myxoid stroma. By immunohistochemistry the lesional cells expressed NKI/C3, microphthalmia transcription factor (MiTF), and CD68, with focal staining for PGP9.5, factor XIIIa, and CD10 also observed. The tumors were negative for S-100, SOX-10, epithelial membrane antigen, desmin, smooth muscle actin, glial fibrillary acid protein, and CD34. The present case confirms that cellular neurothekeoma can present clinically as multiple lesions and can have a predominantly myxoid appearance, potentially mimicking other cutaneous myxoid lesions.


Subject(s)
Lupus Erythematosus, Systemic/complications , Nervous System Neoplasms/pathology , Neurothekeoma/diagnosis , Skin Neoplasms/pathology , Adolescent , Adult , Antigens, CD/metabolism , Antigens, Differentiation, Myelomonocytic/metabolism , Biomarkers, Tumor/metabolism , Child , Child, Preschool , Diagnosis, Differential , Epithelioid Cells/pathology , Factor XIIIa/metabolism , Female , Humans , Immunohistochemistry/methods , Infant , Male , Microphthalmia-Associated Transcription Factor/metabolism , Middle Aged , Myxoma/pathology , Neprilysin/metabolism , Neurothekeoma/metabolism , Ubiquitin Thiolesterase/metabolism
4.
Am J Dermatopathol ; 43(8): 588-592, 2021 08 01.
Article in English | MEDLINE | ID: mdl-33606371

ABSTRACT

ABSTRACT: Ossifying plexiform tumor is an exceedingly rare cutaneous neoplasm with distinctive histologic features. The typical microscopic appearance is that of a well-circumscribed dermal lesion composed of spindled and epithelioid cells in a myxoid appearing matrix with a plexiform architecture associated with areas of ossification. The present report details the clinicopathologic features of an ossifying plexiform tumor involving the lower extremity of a 69-year-old man. The cutaneous lesion exhibited characteristic morphologic features of this entity. By immunohistochemistry, the tumor was negative for most markers assessed, but notably exhibited diffuse positivity for SATB2. No lesional recurrence was observed. The present case serves to expand on the limited existing knowledge regarding the clinicopathologic features of this uncommon tumor. The histogenesis of ossifying plexiform tumor remains unclear; however, the demonstration of SATB2 expression in this case suggests osteoblastic differentiation.


Subject(s)
Ossification, Heterotopic/pathology , Skin Neoplasms/pathology , Aged , Epidermis/pathology , Epithelioid Cells/pathology , Humans , Immunohistochemistry , Leg , Male , Matrix Attachment Region Binding Proteins/metabolism , Skin Neoplasms/metabolism , Transcription Factors/metabolism
5.
Pediatr Dermatol ; 38(5): 1102-1110, 2021 Sep.
Article in English | MEDLINE | ID: mdl-33486809

ABSTRACT

BACKGROUND/OBJECTIVES: Pediatric melanoma is rare and remains poorly characterized, especially in racial/ethnic minorities of whom Hispanics are the largest and fastest growing in the United States. The health care burden of melanoma in Hispanics, who often present with more advanced disease, is rising and has even been called an early epidemic in California. We sought to document key clinicopathologic features of melanoma in Hispanic pediatric patients and to compare these parameters to pediatric non-Hispanic whites (NHWs) under the a priori hypothesis that Spitzoid melanomas occur in greater proportions in Hispanics. METHODS: Single-institution cross-sectional study of pediatric melanoma cases (age < 20 years) with Hispanic stratification and comparison with matched Surveillance, Epidemiology, and End Results (SEER) data from the same time frame (1988-2016). RESULTS: Of our 61 institutional cases of pediatric melanoma, Hispanics (11), compared with NHWs (40), presented significantly younger (11.7 years, 95% CI: 2.77-8.00 years; P = .001), with lower limb predominance (46%; P < .05), mostly Spitzoid melanomas (82%; P < .05), and thicker tumors (2.34 mm, CI: 0.26-2.19 mm; P < .05). Similarly, SEER data (2499 cases) showed greater proportions of childhood/pre-pubertal adolescent melanomas (<15 years), lower limb involvement, Spitzoid subtype (36.5% vs 22.5% in NHWs; P = .001), and advanced (regional/distant) disease stages in Hispanics (212) compared with NHWs (2197). CONCLUSIONS: Pediatric melanomas may present differently in Hispanics, and heightened awareness/lower threshold to biopsy high-risk Spitzoid tumors on the lower limb may be warranted. Further investigations are needed to aid prevention and early detection in a vulnerable minority population less likely to seek outpatient dermatology specialty care.


Subject(s)
Melanoma , Nevus, Epithelioid and Spindle Cell , Skin Neoplasms , Adolescent , Adult , Child , Cross-Sectional Studies , Hispanic or Latino , Humans , Melanoma/epidemiology , Skin Neoplasms/epidemiology , United States/epidemiology , Young Adult
6.
Adv Anat Pathol ; 25(4): 282-290, 2018 Jul.
Article in English | MEDLINE | ID: mdl-29649005

ABSTRACT

Smooth muscle tumors occur infrequently in the skin. They consist of a diverse group of lesions representing hamartomas as well as benign and malignant neoplasms. They may arise from arrector pili muscle, specialized smooth muscle of the genitalia, or vascular smooth muscle. Although rare, accurate diagnosis and classification of cutaneous smooth muscle proliferations is important as they can exhibit a range of clinical behavior and may be associated with underlying syndromes. This review summarizes the clinicopathologic spectrum of smooth muscle tumors involving the skin.


Subject(s)
Skin Neoplasms/pathology , Smooth Muscle Tumor/pathology , Humans
7.
J Cutan Pathol ; 45(12): 891-896, 2018 Dec.
Article in English | MEDLINE | ID: mdl-30178478

ABSTRACT

BACKGROUND: Hormonal changes in pregnancy are known to alter melanocytic lesions, with some nevi noted to have increased mitotic figures and increased Ki-67 proliferation index. Additionally, cytomorphologic changes have also been noted, referred to as superficial micronodules of pregnancy. These changes may alarm the pathologist for malignancy, particularly nevoid melanoma. Immunohistochemistry for p16 has been recently utilized to distinguish benign nevi from melanoma. We assessed the use of p16 immunohistochemistry for distinguishing melanocytic nevi of pregnant patients from nevoid melanomas. METHODS: Fourteen nevomelanocytic lesions were obtained from pregnant or postpartum patients along with 20 nevoid melanomas for comparison. Immunohistochemistry with p16 was performed on each melanocytic lesion. The percentage of nuclear p16 staining of dermal melanocytes was grouped on a scale of <5%, 5% to 25%, >25% to 50%, and >50%. RESULTS: The majority of nevi from pregnant patients (81%) showed staining of >5% for p16. In contrast, the majority of nevoid melanomas (65%) had staining of <5% for p16. CONCLUSION: The application of p16 as a potential immunohistochemistry diagnostic marker to distinguish nevi from pregnant patients vs nevoid melanomas may be useful.


Subject(s)
Biomarkers, Tumor/biosynthesis , Cyclin-Dependent Kinase Inhibitor p16/biosynthesis , Melanoma , Nevus , Pregnancy Complications, Neoplastic , Skin Neoplasms , Adult , Female , Humans , Immunohistochemistry , Melanoma/metabolism , Melanoma/pathology , Nevus/metabolism , Nevus/pathology , Pregnancy , Pregnancy Complications, Neoplastic/metabolism , Pregnancy Complications, Neoplastic/pathology , Skin Neoplasms/metabolism , Skin Neoplasms/pathology
8.
J Cutan Pathol ; 45(1): 71-73, 2018 Jan.
Article in English | MEDLINE | ID: mdl-29028126

ABSTRACT

Q fever caused by Coxiella burnetii usually presents asymptomatically or as an undifferentiated febrile disease and rarely as rash or other cutaneous manifestations of the disease. Here we present a 41-year-old male complaining of body ache, fever, nausea, malaise, bilateral knee pain and vomiting. Clinical examination revealed a notable erythematous blanching rash all over his body. Workup revealed positive serologic testing for C. burnetii and skin biopsy of the rash revealed leukocytoclastic vasculitis.


Subject(s)
Q Fever/complications , Vasculitis, Leukocytoclastic, Cutaneous/microbiology , Adult , Humans , Male
9.
Mod Pathol ; 25(6): 828-37, 2012 Jun.
Article in English | MEDLINE | ID: mdl-22411186

ABSTRACT

Limited understanding of molecular mechanisms of metastasis in melanoma contributes to the absence of effective treatments. Increased knowledge of alterations in genes that underpin critical molecular events that lead to metastasis is essential. We have investigated the gene expression profiles of primary melanomas and melanoma metastases in sentinel lymph nodes. A total of 19 samples (10 primary melanomas and 9 sentinel lymph node metastases) were evaluated. Melanoma cells were dissected from tissue blocks. Total mRNA was isolated, amplified, and labeled using an Ambion Recover All Total Nucleic Acid Isolation kit, Nu-GEN WT-Ovation formalin-fixed, paraffin-embedded RNA Amplification System, and FL-Ovation cDNA Biotin Module V2, respectively. Samples were hybridized to the Affymetrix Gene Chip Human U133 Plus 2.0 Array. Data were analyzed using Partek Genomics Suite Version 6.4. Genes selected showed ≥2-fold difference in expression and P<5.00E-2. Validation studies used standard immunohistochemical assays. Hierarchical clustering disclosed two distinct groups: 10 primary melanomas and 9 sentinel lymph node metastases. Gene expression analysis identified 576 genes that showed significant differential expression. Most differences reflected decreased gene expression in metastases relative to primaries. Reduced gene expression in primaries was less frequent and less dramatic. Genes significantly increased or decreased in sentinel lymph node metastases were active in cell adhesion/structural integrity, tumor suppression, cell cycle regulation, and apoptosis. Validation studies indicate that MAGEC1 (melanoma antigen family C1) and FCRL1 (Fc receptor-like 1) are involved in melanoma progression. There are striking differential gene expression patterns between primary and nodally metastatic melanomas. Similar findings were seen with autologous paired primary melanomas and sentinel lymph node metastases, supporting involvement of these gene alterations in evolution of metastases. With further study, it may be possible to determine the exact sequence of molecular events that underlie melanoma metastases.


Subject(s)
Biomarkers, Tumor/genetics , Gene Expression Profiling , Lymph Nodes/chemistry , Lymph Nodes/pathology , Melanoma/genetics , Melanoma/secondary , Skin Neoplasms/genetics , Skin Neoplasms/pathology , Adult , Aged , Aged, 80 and over , Antigens, Neoplasm/genetics , Biomarkers, Tumor/analysis , Cluster Analysis , Female , Gene Expression Profiling/methods , Gene Expression Regulation, Neoplastic , Genetic Predisposition to Disease , Humans , Immunohistochemistry , Los Angeles , Lymphatic Metastasis , Male , Melanoma/chemistry , Membrane Proteins/genetics , Middle Aged , Neoplasm Proteins/genetics , New South Wales , Oligonucleotide Array Sequence Analysis , Paraffin Embedding , Phenotype , Principal Component Analysis , RNA, Messenger/analysis , Reproducibility of Results , Sentinel Lymph Node Biopsy , Skin Neoplasms/chemistry
10.
Appl Immunohistochem Mol Morphol ; 30(6): 441-445, 2022 07 01.
Article in English | MEDLINE | ID: mdl-35797676

ABSTRACT

BACKGROUND: Distinction of superficial spreading melanoma (SSM) from compound nevi (CN) sometimes poses difficult diagnostic challenges. Herein, we studied cyclin D1 protein expression by immunohistochemistry in SSM and CN and evaluated the results by digital image analysis. DESIGN: A total of 13 CN and 12 SSM cases were retrospectively reviewed and cyclin D1 immunohistochemistry was performed. Immunohistochemical stained slides were evaluated by digital imaging analysis that included quantification and staining intensity of the cyclin D1 expressing dermal cells. RESULTS: Cyclin D1 expression was observed in all CN and SSM. CN-positive staining was present in 30% to 93% of the dermal nevocytes, more positive in the upper (mean 85%), than lower half (mean 57%). SSM-positive staining was present in 44% to 96% of the dermal lesion, more positive in the upper (mean 88%) than lower half (mean 49%). When analyzed based on 3+ strong staining intensity, similar regional differences in cyclin D1 expression were observed. CONCLUSIONS: Digital image analysis of Cyclin D1 expression showed no differences between CN and SSM. Quantity and regional distribution of cyclin D1 positivity were found to be similar in both lesions. Our findings argue against the routine use of cyclin D1 immunohistochemistry as a diagnostic tool for differentiating CN from SSM.


Subject(s)
Cyclin D1 , Melanoma , Nevus , Skin Neoplasms , Cyclin D1/metabolism , Humans , Melanoma/pathology , Nevus/pathology , Retrospective Studies , Skin Neoplasms/pathology , Melanoma, Cutaneous Malignant
11.
Arch Gynecol Obstet ; 284(1): 183-90, 2011 Jul.
Article in English | MEDLINE | ID: mdl-20680316

ABSTRACT

PURPOSE: To assess known cancer biomarkers CA-125, human tissue kallikreins KLK6 and KLK10, hemostatic markers and age with 5-year survival outcome from epithelial ovarian cancer. METHODS: Forty-one benign cyst cohorts and 83 patients diagnosed with ovarian cancer were recruited. The following assays were performed: fibrinogen, vWF antigen, D: -dimer, ATIII activity, tPA, PAI-1, uPAR, KLK6, KLK10 and CA-125. Follow-up visits of cancer patients of more than 60 months were noted. Data between those who survived past 60 months and mortality from cancer were analyzed. RESULTS: Only 24 patients lived past 60 months, and 31 died (advanced stage n = 27). Those living past 60 months were significantly older and associated with similar pre-operative levels seen in benign cyst cohorts especially for KLK6, fibrinogen, vWF, AT levels despite upregulation of D: -dimer, CA-125 and KLK10. Ovarian cancer cohorts living past 60 months were younger than those who died within 12 months (n = 12). Mortality within 12 months was associated with older age, upregulation of KLK6, fibrinogen, D: -dimer, vWF, tPA antigen and reduced ATIII levels. Similarly, mortality within 36 months of disease showed older age with upregulation of CA-125, KLK6 D: -dimer vWF antigen and tPA antigen levels. Late stage cancer (III/IV) showed upregulated CA-125, KLK6, KLK10, D: -dimer and reduced AT compared to early stage cancer (I/II). The 5-year survival rate for early cancer was 80%, advanced 22.9% and overall 5-year survival rate was 43.6%. CONCLUSION: Older age together with the novel biomarkers studied and their association with adverse outcome from epithelial ovarian cancer was seen especially within 12 and 36 months of disease. Those who lived past 60 months of disease showed similar pre-operative levels seen in benign cyst cohorts despite elevated D: -dimer, CA125 and KLK 10. An enlarged study is needed to confirm these findings.


Subject(s)
CA-125 Antigen/blood , Kallikreins/blood , Neoplasms, Glandular and Epithelial/mortality , Ovarian Neoplasms/mortality , Adult , Age Factors , Female , Hemostasis , Humans , Kaplan-Meier Estimate , Longitudinal Studies , Middle Aged , Neoplasms, Glandular and Epithelial/blood , Neoplasms, Glandular and Epithelial/pathology , Ovarian Cysts/blood , Ovarian Neoplasms/blood , Ovarian Neoplasms/pathology , Ovary/pathology , Retrospective Studies , Singapore/epidemiology
12.
J Obstet Gynaecol Res ; 36(4): 838-44, 2010 Aug.
Article in English | MEDLINE | ID: mdl-20666954

ABSTRACT

AIM: The purpose of the study is to determine the effects of levonorgestrel use on hemostasis, and menstrual blood loss over 24 months in a cohort of women seeking contraception. METHODS: Data from 30 women (median age 36 years) were analyzed. Samplings at pre-insertion, 1 and 3 months for blood and additional endometrial aspirates at 2 and 6 months were performed. Systemic determination for hemoglobin, hematocrit, computerized thromboelastography, tissue-type plasminogen activator, urokinase-like plasminogen activator and receptor, plasminogen activator inhibitor-1/2, D-dimer and von Willebrand Factor was performed. In endometrial extracts, tissue-type plasminogen activator, urokinase-like plasminogen activator and receptor and plasminogen activator inhibitor-1/2 were assayed. The Menstrual Blood Loss Pictorial Chart Score for measurement of menstrual blood loss was carried out for 24 months. RESULTS: There were no significant changes in systemic hemostasis within 3 months of device use. In the endometrium, there was a significant increase in tissue-type plasminogen activator antigen, plasminogen activator inhibitor-1/2 and urokinase-like plasminogen activator receptor levels from pre-insertion state, with the highest level seen by 6 months. Amenorrhea was seen in 20% of women by 6 months and 50% by 24 months. CONCLUSIONS: Enhanced expression of plasminogen activator inhibitor-1/2 in the presence of increased urokinase-like plasminogen activator receptor and tissue-type plasminogen activator antigen was seen in the endometrium. The effects on hemostasis appear to be localized in the endometrium. Systemic hemostasis was not duly affected and menstrual blood loss was reduced. No women in the study had a pregnancy or expulsion of the levonorgestrel-intrauterine system device in the 24 months of the study period.


Subject(s)
Endometrium/drug effects , Hemostasis/drug effects , Intrauterine Devices, Medicated , Levonorgestrel/pharmacology , Menstruation/blood , Menstruation/drug effects , Adult , Enzyme-Linked Immunosorbent Assay , Female , Humans , Patient Selection , Statistics, Nonparametric , Tissue Plasminogen Activator/blood
13.
Head Neck Pathol ; 14(3): 571-576, 2020 Sep.
Article in English | MEDLINE | ID: mdl-31485983

ABSTRACT

Schwannomas commonly occur in the head and neck but infrequently involve the oral cavity and rarely affect the tongue. The clinical and pathologic features of 19 cases of schwannoma arising in the tongue were analyzed. There were 13 males and 6 females ranging in age from 12 to 82 years (mean 34 years; median 29 years). The majority of tumors presented as an asymptomatic mass localized to the anterior two-thirds of the tongue. Histologically, 18 schwannomas exhibited characteristic Antoni A and B areas with the former pattern predominating. One tumor was composed exclusively of cellular Antoni A tissue and was classified as a cellular schwannoma. Tumor encapsulation was variable with nearly half of the lesions lacking a well-defined fibrous capsule. All were strongly and diffusely positive for S-100 protein. No recurrences were observed on clinical follow-up. Schwannoma of the tongue, although rare, should be separated from other types of lingual nerve sheath proliferations and tumors.


Subject(s)
Neurilemmoma/pathology , Tongue Neoplasms/pathology , Adolescent , Adult , Aged , Aged, 80 and over , Child , Female , Humans , Male , Middle Aged , Young Adult
14.
Head Neck Pathol ; 14(2): 374-380, 2020 Jun.
Article in English | MEDLINE | ID: mdl-31111316

ABSTRACT

Neurofibromas rarely occur within the oral cavity and infrequently involve the tongue. The majority of lingual neurofibromas arise in patients affected by neurofibromatosis type 1 (NF1). Neurofibromas of the tongue unassociated with this disorder are exceedingly uncommon. The clinical and pathologic features of 10 cases of sporadic lingual neurofibromas, unassociated with NF1, were evaluated. The patients included six females and four males ranging in age from 30 to 69 years (mean 59 years; median 63 years). An asymptomatic or slowly enlarging lingual mass was the most common clinical presentation. None of the patients were documented to have NF1. Histologically, the tumors were unencapsulated and situated beneath an intact squamous mucosa. The tumors are comprised of spindle cells with wavy nuclei within a collagenous to myxoid stroma. One tumor was characterized by a plexiform growth pattern. The lesional cells were positive for S-100 protein. Clinical follow up, available for all patients, showed no recurrences and no subsequent development of additional clinical manifestations of NF1. Lingual neurofibromas should be distinguished from other peripheral nerve sheath tumors that can affect this anatomic site. This series of cases confirms that sporadic neurofibromas of the tongue may be rarely encountered in patients having no other features of NF1.


Subject(s)
Neurofibroma/pathology , Tongue Neoplasms/pathology , Adult , Aged , Female , Humans , Male , Middle Aged , Neurofibromatosis 1
15.
Mod Pathol ; 22(4): 538-46, 2009 Apr.
Article in English | MEDLINE | ID: mdl-19270649

ABSTRACT

Melanoma may be difficult to identify histologically and relatively high rates of misdiagnosis leads to many malpractice claims. Currently separation of melanomas from nevi is based primarily on light microscopic interpretation of hematoxylin and eosin stained sections with limited assistance from immunohistology. To increase the accuracy of discrimination of benign and malignant melanocytic lesions we identified DNA microarray-derived gene expression profiles of different melanocytic lesions and evaluated the performance of these gene signatures as molecular diagnostic tools in the molecular classification and separation of melanomas and nevi. Melanocyte-derived cells were isolated by laser capture microdissection from 165 formalin-fixed and paraffin-embedded melanocytic nevi and melanoma tissue sections. RNA was isolated, amplified, labeled, and hybridized to a custom DNA microarray. In all 120 samples were used to identify differentially expressed genes and generate a gene expression classifier capable of distinguishing between melanomas and nevi. These classifiers were tested by the leave-one-out method and in a blinded study. RT-PCR verified the results. Unsupervised hierarchical clustering identified two distinct lesional groups that closely correlated with the histopathologically identified melanomas and nevi. Analysis of gene expression levels identified 36 significant differentially expressed genes. In comparison with nevi, melanomas expressed higher levels of genes promoting signal transduction, transcription, and cell growth. In contrast, expression of L1CAM (homolog) was reduced in melanomas relative to nevi. Genes differentially expressed in melanomas and nevi, on the basis of molecular signal, sub classified a group of unknown melanocytic lesions as melanomas or nevi and had high concordance rates with histopathology. Gene signatures established using DNA microarray gene expression profiling can distinguish melanomas from nevi, indicating the feasibility of using molecular classification as a supplement to standard histology. Our successful use of a standard formalin-fixed and paraffin-embedded tissue further supports the practicability of combining molecular diagnostic testing with histopathology in evaluation of difficult melanocytic lesions.


Subject(s)
Gene Expression Profiling , Melanoma/genetics , Nevus, Pigmented/genetics , Skin Neoplasms/genetics , Diagnosis, Differential , Formaldehyde , Humans , In Situ Hybridization , Melanoma/classification , Melanoma/diagnosis , Microdissection , Nevus, Pigmented/classification , Nevus, Pigmented/diagnosis , Oligonucleotide Array Sequence Analysis , Paraffin Embedding , Reverse Transcriptase Polymerase Chain Reaction , Skin Neoplasms/classification , Skin Neoplasms/diagnosis , Tissue Fixation
16.
Open Access Maced J Med Sci ; 7(14): 2221-2225, 2019 Jul 30.
Article in English | MEDLINE | ID: mdl-31592071

ABSTRACT

BACKGROUND: Dengue fever is the most serious consequence of mosquito-borne infection worldwide. The pathophysiology of DHF in human is complex, which involve endothelial cell activation and impaired endothelial barrier leading to plasma leakage triggering the activation of the haemostatic system. The increased vascular permeability may lead to hypovolemia, hypotension and shock, which is life-threatening. AIM: The objective of the study was to determine the effects of dengue haemorrhagic fever on the vascular endothelium. METHODS: Fifty patients (males 34, females 16), were recruited, Grade 1 (n = 41), Grade 2 (n = 6), Grade 3 (n = 2) and Grade 4 (n = 1) DHF. Blood sampling was performed at the febrile, defervescence and convalescent phases for the determination of haemoglobin, haematocrit, platelets, prothrombin fragment F1 + 2, Von Willebrand Factor (VWF), vascular endothelial growth factor (VEGF) and D-dimer levels. Fifteen normal subjects were recruited to serve as normal controls. RESULTS: The patients aged between 4 and 54 years old. Grades 1 & 2 DHF showed no significant differences in the parameters studied. However, thrombocytopenia, elevated F1 + 2, VWF, VEGF and D-dimer levels were evident in febrile, defervescence and convalescent phases suggesting endothelial activation and plasma leakage. Pleural effusion was observed only in severe DHF. The three patients with Grades 3 and 4 DHF had similar study results. No mortality was recorded in the study. CONCLUSION: In dengue haemorrhagic fever, the vascular endothelium is activated, causing plasma leakage triggering the activation of the haemostatic system creating a hypercoagulable and enhanced fibrinolytic state evident by marked fibrinolysis.

17.
Arch Pathol Lab Med ; 142(7): 815-828, 2018 07.
Article in English | MEDLINE | ID: mdl-29939777

ABSTRACT

CONTEXT: - Making an accurate diagnosis for melanocytic lesions has always been challenging for pathologists, especially when dealing with difficult-to-diagnose cases. Misdiagnosis of melanoma and melanocytic lesions in general has tremendous medical-legal implications, often leading to unnecessary and excessive use of adjunctive tests. Although molecular testing is of much interest and there is great support for its development, currently, for most melanocytic lesions, immunohistochemical studies remain the most practical method for assistance in the routine diagnosis of melanocytic lesions for the average pathologist. OBJECTIVES: - To review the practical use of p16 immunohistochemistry for evaluating melanocytic lesions, particularly for differentiating benign from malignant tumors, and to perform a meta-analysis of primary studies evaluating p16 immunohistochemistry in melanocytic lesions. DATA SOURCES: - A PubMed database search for literature reporting melanocytic lesions and p16 immunohistochemistry was performed. Essential information from each study (number of samples, antibody used, collection dates, overall p16 immunohistochemistry results, and general method of interpretation) was tabulated and analyzed. Examples of representative cases showing p16 immunostaining pattern are also illustrated. CONCLUSIONS: - Incorporation of p16 immunohistochemistry for the diagnosis of melanocytic lesions is of limited use, especially for the purpose of differentiating benign from malignant lesions. Evaluation of multiple studies reveals a wide range of results. However, there appears to be some value for the use of p16 in distinguishing nodal nevi from metastatic melanoma within nodes. The method of interpretation (nuclear versus cytoplasmic staining) also appears to give differing results, as studies considering only nuclear staining appeared to show more consistent results from study to study.


Subject(s)
Biomarkers, Tumor/metabolism , Cyclin-Dependent Kinase Inhibitor p16/metabolism , Melanoma/diagnosis , Nevus/diagnosis , Diagnosis, Differential , Humans , Immunohistochemistry , Melanocytes/pathology , Melanoma/metabolism , Melanoma/pathology , Nevus/metabolism , Nevus/pathology
18.
Mol Cell Biol ; 22(11): 3621-32, 2002 Jun.
Article in English | MEDLINE | ID: mdl-11997499

ABSTRACT

Hormone-activated nuclear receptors (NR) bind to specific regulatory DNA elements associated with their target genes and recruit coactivator proteins to remodel chromatin structure, recruit RNA polymerase, and activate transcription. The p160 coactivators (e.g., SRC-1, GRIP1, and ACTR) bind directly to activated NR and can recruit a variety of secondary coactivators. We have established a transient-transfection assay system under which the activity of various NR is highly or completely dependent on synergistic cooperation among three classes of coactivators: a p160 coactivator, the protein methyltransferase CARM1, and any of the three protein acetyltransferases, p300, CBP, or p/CAF. The three-coactivator functional synergy was only observed when low levels of NR were expressed and was highly or completely dependent on the methyltransferase activity of CARM1 and the acetyltransferase activity of p/CAF, but not the acetyltransferase activity of p300. Other members of the protein arginine methyltransferase family, which methylate different protein substrates than CARM1, could not substitute for CARM1 to act synergistically with p300 or p/CAF. A ternary complex of GRIP1, CARM1, and p300 or CBP was demonstrated in cultured mammalian cells, supporting a physiological role for the observed synergy. The transfection assay described here is a valuable new tool for investigating the mechanism of coactivator function and demonstrates the importance of multiple coactivators, including CARM1 and its specific protein methyltransferase activity, in transcriptional activation.


Subject(s)
Acetyltransferases/metabolism , Protein Methyltransferases/metabolism , Receptors, Cytoplasmic and Nuclear/metabolism , Acetyltransferases/genetics , Animals , COS Cells , Cell Cycle Proteins/genetics , Cell Cycle Proteins/metabolism , Cell Line , Histone Acetyltransferases , Humans , Models, Biological , Nuclear Receptor Coactivator 2 , Protein Methyltransferases/genetics , Protein-Arginine N-Methyltransferases/genetics , Protein-Arginine N-Methyltransferases/metabolism , Rats , Transcription Factors/genetics , Transcription Factors/metabolism , Transcriptional Activation , Transfection , p300-CBP Transcription Factors
20.
Clin Appl Thromb Hemost ; 12(1): 3-8, 2006 Jan.
Article in English | MEDLINE | ID: mdl-16444428

ABSTRACT

Thirty-five patients diagnosed to have ovarian cancer (early FIGO stage I/II n = 11, advanced FIGO stage III/IV, n = 24) were evaluated for hemostatic parameters relating to survival outcome by 36 months of disease. Systemic plasminogen activators and inhibitors were evaluated and we found no significant association with survival outcome and eventually only fibrinogen, von Willebrand Factor (vWF), antithrombin III (ATIII), and D-dimer levels were determined for their association with disease outcome by 12 months, 24 months, and 36 months. Twenty-four patients succumbed to the disease by 36 months (early n = 2, advanced n = 22). The 11 surviving patients (advanced n = 3, including one deceased at 52 months) is still living past 36 months and 82 months at the time of analysis. Elevated fibrinogen, vWF, and D-dimer together with reduced ATIII levels were found to be associated with poor survival outcome by 12 months of disease. Moreover, elevated vWF and D-dimer with reduced ATIII levels was strongly implicated with poor survival outcome by 36 months from ovarian cancer. The overall survival rate at 36 months from ovarian cancer was 31.4%. It is therefore suggested that fibrinogen, vWF, ATIII, and D-dimer levels be used together as prognostic markers for disease outcome especially in patients with advanced ovarian cancer within 36 months of disease. An expanded study is required to confirm these findings.


Subject(s)
Ovarian Neoplasms/blood , Ovarian Neoplasms/mortality , Adolescent , Adult , Aged , Aged, 80 and over , Antithrombin III/analysis , Biomarkers/blood , Female , Fibrin Fibrinogen Degradation Products/analysis , Fibrinogen/analysis , Humans , Middle Aged , Prognosis , Survival Analysis , von Willebrand Factor/analysis
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