Remains your authoritative source for comprehensive coverage of those skin diseases in which histopathology plays an important role in diagnosis. This edition maintains the proven, clinicopathologic classification of cutaneous disease while incorporating a “primer” on pattern-algorithm diagnosis. More than 1,800 full-color illustrations, including photomicrographs and clinical photographs, help you visualize and make the most of the clinical diagnostic process.

Lever's Histopathology of the Skin

https://jcp.bmj.com/content/jclinpath/35/1/123.2.full.pdf

Ackerman's Surgical Pathology

Three months ago, a 50-year-old man who was otherwise in good health noticed a hard, round nodule on his left arm. Within 2 months, similar nodules appeared all over his trunk, head, arms, and legs. The reddish purple lesions, less than 2 cm in diameter, were painless and slightly pruritic.

Cutaneous T-Cell Lymphoma

Immune checkpoint inhibitors have revolutionized the treatment of patients with advanced-stage metastatic melanoma, as well as patients with many other solid cancers, yielding long-lasting responses and improved survival. However, a subset of patients who initially respond to immunotherapy, later relapse and develop therapy resistance (termed "acquired resistance"), whereas others do not respond at all (termed "primary resistance"). Primary and acquired resistance are key clinical barriers to further improving outcomes of patients with metastatic melanoma, and the known mechanisms underlying each involves various components of the cancer immune cycle, and interactions between multiple signaling molecules and pathways. Due to this complexity, current knowledge on resistance mechanisms is still incomplete. Overcoming therapy resistance requires a thorough understanding of the mechanisms underlying immune evasion by tumors. In this review, we explore the mechanisms of primary and acquired resistance to immunotherapy in melanoma and detail potential therapeutic strategies to prevent and overcome them. Clin Cancer Res; 24(6); 1260-70. ©2017 AACR.

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Primary and Acquired Resistance to Immune Checkpoint Inhibitors in Metastatic Melanoma.

BACKGROUND Melanoma is the most serious skin cancer. There is an established correlation between thickness and aggressiveness of the tumor. Nevertheless, the potential value of vascular endothelial growth factor (VEGF) in correlation with tumor progression remains unresolved. MATERIALS AND METHODS Thirty seven paraffin blocks of cutaneous melanoma were obtained from Pathology department of Al-zahra hospital between 2005 and 2010. The sections were stained with monoclonal mouse antibodies (mAbs) against vascular endothelial growth factor A and evaluated by distribution of expression of VEGF in tumor cells as 0, 0%; 1, 1%--25%; 2, 25%--50%; 3, >50% and the staining intensity from 0 (negative) to 3 (strong). The sum of intensity score and distribution score was then calculated as the VEGF index. The relationship between VEGF expression (distribution, intensity, and index) and tumor progression (vertical and radial growth, Clark's level, and Breslow's depth) was studied. SPSS software was used to analyze the data by ANOVA, and chi-square tests. RESULTS 51.4% of the patients showed vertical growth pattern. Mean Breslow's depth was 1.84 ± 1.79 mm. There was a significant association between growth pattern and VEGF distribution, intensity and index (P = 0.006, P = 0.005, and P = 0.001 respectively). VEGF distribution, intensity, and index all had correlation with Breslow's depth as well (ANOVA test: P = 0.003, P < 0.001, and P < 0.001 respectively) VEGF index had also correlation with Clark's level, but this was not seen for VEGF distribution and intensity. CONCLUSION VEGF expression (both VEGF distribution and intensity) is associated with progression of malignant melanoma. VEGF index can explain this association better.

http://jrms.mui.ac.ir/index.php/jrms/article/download/8487/3633

The role of VEGF in melanoma progression.

Purpose Epithelixal ovarian cancer is the fourth cause of cancer death in developed countries with 77% of ovarian cancer cases diagnosed with regional or distant metastasis, with poor survival rates. Docetaxel (DTX) is a well-known anticancer agent, with clinically proven efficacy in several malignancies, including ovarian cancer. However, the adverse effects caused by the active ingredient or currently marketed formulations could even deprive the patient of the advantages of treatment. Therefore, in the current study, polymeric nanoparticles (NPs) equipped with aptamer molecules as targeting agents were proposed to minimize the adverse effects and enhance the antitumor efficacy through directing the drug cargo toward its site of action. Materials and methods Electrospraying technique was implemented to fabricate poly (butylene adipate-co-butylene terephthalate) (Ecoflex®) NPs loaded with DTX (DTX-NPs). Afterward, aptamer molecules were added to the DTX-NPs, which bound via covalent bonds (Apt-DTX-NPs). The particle size, size distribution, zeta potential, entrapment efficiency, and release profile of the NPs were characterized. Using MTT assay and flow-cytometry analysis, the in vitro cytotoxicity and cellular uptake of the NPs were compared to those of the free drug. Following intravenous administration of Taxotere®, DTX-NPs, and Apt-DTX-NPs (at an equivalent dose of 5 mg/kg of DTX), pharmacokinetic parameters and antitumor efficacy were compared in female Balb/c and HER-2-overexpressing tumor-bearing B6 athymic mice, respectively. Results The obtained results demonstrated significantly enhanced in vitro cytotoxicity and cellular uptake of Apt-DTX-NPs in a HER-2-overexpressing cell line, comparing to DTX-NPs and the free drug. The results of in vivo studies indicated significant increment in pharmacokinetic parameters including the area under the plasma concentration-time curve, mean residence time, and elimination half-life. Significant increment in antitumor efficacy was also observed, probably due to the targeted delivery of DTX to the tumor site and enhanced cellular uptake as evaluated in the aforementioned tests. Conclusion Hence, the proposed drug delivery system could be considered as an appropriate potential substitute for currently marketed DTX formulations.

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Pharmacokinetics and in vitro/in vivo antitumor efficacy of aptamer-targeted Ecoflex® nanoparticles for docetaxel delivery in ovarian cancer.

Cadmium (Cd) is a highly toxic element, which may cause toxicity to most organs in the body. Zinc (Zn) and magnesium (Mg) are essential minerals with probable benefits on Cd harmful effects. Finding an efficient and non-pathological treatment against Cd toxicity seems promising. Fifty adult rats were divided into ten experimental groups of five rats each. The Cd group was treated with 1 mg Cd/kg and the control group received 0.5 cm3 normal saline. The other eight groups received Zn (0.5 and 1.5 mg/kg) and Mg (0.5 and 1.5 mg/kg) either alone or in combination with 1 mg Cd/kg through IP injection for 3 weeks. Testis malondialdehyde (MDA), sperm parameters, and testis histopathology were investigated. Cd reduced sperm parameters and increased testis MDA. Moreover, Cd exposure caused a significant histological damage in testis of male rats. However, Zn or Mg treatment prevented and reversed Cd toxic alterations in testis. These findings suggest that co-administration of Zn or Mg could improve cadmium testicular toxicity in male Wistar rats.

Cadmium Testicular Toxicity in Male Wistar Rats: Protective Roles of Zinc and Magnesium

Background Down-regulation of the epithelial cell-cell adhesion molecule E-cadherin is frequently associated with tumor formation and progression in breast cancer. The aim of this study is the assessment of relationship between E-cadherin expression and routine prognostic biomarkers as well as grading and lymph node status in breast invasive ductal carcinomas. . The associations between co-expression of E-cadherin and other biomarkers on one hand and grading, proliferating index and lymph node status on the other have also been evaluated. Objective To evaluate the correlation of E-cadherin expression and routine immunohistochemistry panel in breast invasive ductal carcinoma. Methods 108 formalin-fixed and paraffin-embedded breast cancer specimens (of invasive ductal carcinoma "NOS" type) from the pathology archive of Alzahra hospital(Isfahan, Iran) which had been studied for expression of routine molecular biomarkers were selected. E-cadherin expression was detected by immunohistochemistry. Stained sections were classified according to the intensity of staining and the percentage of cells showing E-cadherin staining. Results No association was found between E-cadherin alteration and ER, PR, p53, Ki67 and HER2/neu status of breast cancer. However, E-cadherin alteration showed a significant difference between grading and also lymph node groups. There was no association between co-expression of E-cadherin/ER, E-cadherin/PR, E-cadherin/Her-2neu, E-cadherin/p53 and Her-2neu/p53 on one hand and Ki67 status and tumor grade on the other. Co-expressions of E-cadherin/Her-2neu and E-cadherin/p53 showed significant difference in lymph node groups. Conclusion We found that E-cadherin alteration in breast cancer has an association with other important prognostic factors. Evaluation of E-cadherin status can help, independently or in addition to conventional biological prognostic markers, to identify prognosis of breast cancer.

Correlation of E-cadherin expression and routine immunohistochemistry panel in breast invasive ductal carcinoma

BACKGROUND: The distinction between basal cell carcinoma (BCC) and trichoepithelioma (TE) may be very difficult in some cases because of the close similarities of these two lesions clinically and histopathologically. The purpose of this study is to investigate the usefulness of CD10 in distinguishing BCC and TE. METHODS: The immunohistochemical expression of CD10 was evaluated in an archived group of 30 BCCs and 12 TEs in a retrospective cross sectional study. The localization of anti-CD10 to the tumoral and/or stromal cells was determined in each case and was compared between these two tumors using Fisher's Exact Test. RESULTS: In BCC cases, the expression of CD10 was noted in tumoral cells in 26 cases (83.2%). Of these, 3 cases showed positivity of the stromal and basaloid cells, two cases demonstrated stromal expression alone and two BCCs were not immunoreactive. On the other hand, 10 out of 12 (83.3%) TEs showed positive stromal immunoreactivity. Of these, one case also showed positivity of the basaloid cells. One TE demonstrated epithelial expression alone and one TE was not immunoreactive. The pattern of staining of basaloid cells and stromal cells in BCC and trichoepithelioma was statistically different (P < 0.001). CONCLUSIONS: We conclude that CD10 is a useful marker in the differential diagnosis of BCC versus TE. KEYWORDS: Basal Cell Carcinoma, Trichoepithelioma, CD10. BACKGROUND: The distinction between basal cell carcinoma (BCC) and trichoepithelioma (TE) may be very difficult in some cases because of the close similarities of these two lesions clinically and histopathologically. The purpose of this study is to investigate the usefulness of CD10 in distinguishing BCC and TE. METHODS: The immunohistochemical expression of CD10 was evaluated in an archived group of 30 BCCs and 12 TEs in a retrospective cross sectional study. The localization of anti-CD10 to the tumoral and/or stromal cells was determined in each case and was compared between these two tumors using Fisher's Exact Test. RESULTS: In BCC cases, the expression of CD10 was noted in tumoral cells in 26 cases (83.2%). Of these, 3 cases showed positivity of the stromal and basaloid cells, two cases demonstrated stromal expression alone and two BCCs were not immunoreactive. On the other hand, 10 out of 12 (83.3%) TEs showed positive stromal immunoreactivity. Of these, one case also showed positivity of the basaloid cells. One TE demonstrated epithelial expression alone and one TE was not immunoreactive. The pattern of staining of basaloid cells and stromal cells in BCC and trichoepithelioma was statistically different (p < 0.001). CONCLUSIONS: We conclude that CD10 is a useful marker in the differential diagnosis of BCC versus TE. KEYWORDS: Basal Cell Carcinoma, Trichoepithelioma, CD10. BACKGROUND: The distinction between basal cell carcinoma (BCC) and trichoepithelioma (TE) may be very difficult in some cases because of the close similarities of these two lesions clinically and histopathologically. The purpose of this study is to investigate the usefulness of CD10 in distinguishing BCC and TE. METHODS: The immunohistochemical expression of CD10 was evaluated in an archived group of 30 BCCs and 12 TEs in a retrospective cross sectional study. The localization of anti-CD10 to the tumoral and/or stromal cells was determined in each case and was compared between these two tumors using Fisher's Exact Test. RESULTS: In BCC cases, the expression of CD10 was noted in tumoral cells in 26 cases (83.2%). Of these, 3 cases showed positivity of the stromal and basaloid cells, two cases demonstrated stromal expression alone and two BCCs were not immunoreactive. On the other hand, 10 out of 12 (83.3%) TEs showed positive stromal immunoreactivity. Of these, one case also showed positivity of the basaloid cells. One TE demonstrated epithelial expression alone and one TE was not immunoreactive. The pattern of staining of basaloid cells and stromal cells in BCC and trichoepithelioma was statistically different (p < 0.001). CONCLUSIONS: We conclude that CD10 is a useful marker in the differential diagnosis of BCC versus TE. KEYWORDS: Basal Cell Carcinoma, Trichoepithelioma, CD10.

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Parvin Rajabi

Papers

The role of VEGF in melanoma progression.

Pharmacokinetics and in vitro/in vivo antitumor efficacy of aptamer-targeted Ecoflex® nanoparticles for docetaxel delivery in ovarian cancer.

Cadmium Testicular Toxicity in Male Wistar Rats: Protective Roles of Zinc and Magnesium

Correlation of E-cadherin expression and routine immunohistochemistry panel in breast invasive ductal carcinoma

CD10 expression helps to differentiate basal cell carcinoma from trichoepithelioma