Evaluation of MMP-9, MMP-13, MMP-21, and TIMP-1 expressions in malign melanom, dysplastic nevi, and banal nevi.

OBJECTIVE: Although the role of MMPs in the pathogenesis of melanoma is known, few studies have investigated their role in the development of nevi and dysplastic nevi. This study aims to search the expression differences of MMP-9, MMP-13, MMP-21, and TIMP-1 between malignant melanoma (MM), intradermal nevi (IDN), and dysplastic nevi (DN). METHODS: MMP-9, MMP-13, MMP-21, and TIMP-1 antibodies were studied immunohistochemically for 60 cases in our pathology clinic archive between 2013 and 2014. RESULTS: The MM group had the highest expression percentage and intensity for MMP-9 (p<0.001). There was no statistical significance between MMP-13 expression intensities of lesion cells and stromal cells and stromal expression intensities (p>0.05). MMP-21 lesion staining intensities in DN and MM compared to IDN were statistically significant (p=0.001, p=0.011, respectively). For TIMP-1, there was a significant difference between the IDN and the MM group regarding the staining proportion of lesion cells (p<0.01). There was a statistically significant difference in all groups according to lesion cells' expression intensity. (IDN-DN p<0.001, IDN-MM p=0.044, DN-MM p<0.001). CONCLUSION: The following markers can be helpful when lesions cannot be differentiated; increased staining proportions and intensity of MMP-9 in both lesion and stromal cells favor MM in cases where MM and IDN cannot be differentiated. The increased MMP-13 staining proportion of lesion cells can favor DN in cases where the pathologist cannot differentiate DN and MM. Intense expression of MMP-21 by lesion cells can be a potential marker for evaluating the lesion in favor of DN in cases where DN and IDN cannot be differentiated. The high expression intensity of TIMP-1 in lesion cells can favor DN in cases where there is ambiguity between DN and MM. High expression proportion and intensity of stromal cells of TIMP-1 can be useable in favor of MM in cases where MM and DN cannot be differentiated.

Correlation Between Clinical and Histological Features of Dermatopathic Lymphadenopathy: Analysis of 39 Lymph Nodes.

Background. Dermatopathic lymphadenopathy is a well-defined histopathological entity with an underestimated prevalence in the general population. Objective. The present study was conducted to analyze the characteristics of histologically diagnosed cases of dermatopathic lymphadenopathy at our unit. We also aimed to investigate any association between the clinical features of the patients and the histological findings. Methods. A total of 39 lymph node samples from 39 patients diagnosed with dermatopathic lymphadenopathy were included in this prospective cohort study. Results. Thirty-four (87%) patients had a dermatological disorder. The presence of paracortical eosinophils were significantly higher in patients with dermatological disorders (P = .001), while the presence of dilated sinuses was significantly more common in patients without a dermatological disorder (P = .035). The presence of dilated sinuses and medullary histiocytes were significantly more common in patients with lower body surface area involvement of the disease compared to the ones with a higher body surface area (P = .003, P = .034; respectively). Conclusion. Most of the patients included in the study had one of a broad spectrum of undiagnosed dermatological disorders. The clinical significance of the relation between histological and clinical findings in dermatopathic lymphadenopathy remains to be explained. Dermatopathic lymphadenopathy should always be considered in differential diagnoses of patients with persistent lymph node enlargement even when absolute dermatological disorders are not present. Since various skin disorders may be the cause of lymphadenopathy, performing a full-body examination before lymph node excision might prevent unneccessary procedures.

High Incidence of Appendiceal Neoplasms in the Elderly: A Critical Concern for Non-Surgical Treatment.

OBJECTIVE: Appendiceal neoplasms (ANs) are rare tumors that are often discovered incidentally during histopathological examinations. The increasing incidence of ANs is a critical issue in the non-operative management of acute appendicitis. This study aimed to document the temporal trends over a 12-year period by analyzing the clinical presentation, imaging findings, and histopathological features of ANs. SUBJECTS AND METHODS: Health records of patients who underwent appendectomy from 2011 to 2022 were examined. Demographic and clinical data, laboratory results, imaging findings, and histopathological features were documented. The characteristics of both ANs and non-neoplastic cases were evaluated. RESULTS: A total of 22,304 cases were identified, of which 330 (1.5%) were diagnosed with ANs. The odds ratio for ANs increased with age, with the highest odds ratio observed in patients aged 70 or older. Receiver Operating Characteristic analysis showed that age and appendiceal diameter were significant predictors of ANs. An optimal age cut-off point of 28.5 years was determined, yielding a sensitivity of 72% and a specificity of 64%. For appendiceal diameter, the optimal cut-off was found to be 9.5 mm, exhibiting a sensitivity of 77% and a specificity of 56%. CONCLUSION: Although the incidence of ANs remains relatively low, a steady increase has been observed over the past decade. The increasing rate of ANs raises concerns regarding non-surgical management options. The results of this study highlight the importance of considering ANs as a potential diagnosis in older patients and in patients with an appendix diameter greater than 9.5 mm. These findings may have implications for treatment and management.

Targeting prostate cancer with docetaxel-loaded peptide 563-conjugated PEtOx-co-PEI30%-b-PCL polymeric micelle nanocarriers.

Prostate cancer is a global disease that negatively affects the quality of life. Although various strategies against prostate cancer have been developed, only a few achieved tumor-specific targeting. Therefore, a special emphasis has been placed on the treatment of cancer using nano-carrier-encapsulated chemotherapeutic agents conjugated with tumor-homing peptides. The targeting strategy coupling the drugs with nanotechnology helps to overcome the most common barriers, such as high toxicity and side effects. Prostate-specific membrane antigen has emerged as a promising target molecule for prostate cancer and shown to be targeted with high affinity by GRFLTGGTGRLLRIS peptide known as peptide 563 (P563). Here, we aimed to assess the in vitro and in vivo targeting efficiency, safety, and efficacy of P563-conjugated, docetaxel (DTX)-loaded polymeric micelle nanoparticles (P563-PEtOx-co-PEI30%-b-PCL-DTX) against prostate cancer. To this end, we analyzed the cytotoxic activity of P563-PEtOx-co-PEI30%-b-PCL and P563-PEtOx-co-PEI30%-b-PCL-DTX by a cell proliferation assay using PNT1A and 22Rv1 cells. We have also determined the targeting selectivity of P563-PEtOx-co-PEI30%-b-PCL-FITC by flow cytometry and assessed the induction of cell death by western blot and TUNEL assays for P563-PEtOx-co-PEI30%-b-PCL-DTX in 22Rv1 cells. To investigate the in vivo efficacy, we administered DTX in the free form or in polymeric micelle nanoparticles to athymic CD-1 nu/nu mice 22Rv1 xenograft models and performed histopathological analyses. Our study showed that targeting prostate cancer with P563-conjugated PEtOx-co-PEI30%-b-PCL polymeric micelles could exert a potent anti-cancer activity with low side effects.

Delivery of doxorubicin loaded P18 conjugated-poly(2-ethyl-oxazoline)-DOPE nanoliposomes for targeted therapy of breast cancer.

Breast cancer, a heterogeneous disease, has the highest incidence rate and is a major cause of death in females worldwide. Drug delivery by using nanotechnology has shown great promise for improving cancer treatment. Nanoliposomes are known to have enhanced accumulation ability in tumors due to prolonged systemic circulation. Peptide 18 (P18), a tumor homing peptide targeting keratin-1 (KRT-1), was previously shown to have high binding affinity towards breast cancer cells. In this study, we investigate the ability of P18 conjugated PEtOx-DOPE nanoliposomes (P18-PEtOx-DOPE) for the targeted delivery of doxorubicin to AU565 breast cancer model. Toxicology studies of PEtOx-DOPE nanoliposomes performed on normal breast epithelial cells (MCF10A), showed minimal toxicity. Doxorubicin delivery by P18-PEtOx-DOPE to AU565 cells induces cytotoxicity in a dose and time dependent manner causing mitotic arrest in G2/M phase at 24 h. Anti-cancer activity of P18-PEtOx-DOPE-DOX nanoliposomes on AU565 cells was detected by Annexin V/PI apoptosis assay. In terms of in vivo antitumor efficacy, P18-PEtOx-DOPE-DOX nanoliposomes administration to AU565 CD-1 nu/nu mice model showed significant decrease in tumor volume suggesting that DOX delivered by these nanoliposomes elicited a strong antitumor response comparable to the free delivery of doxorubicin. Overall, our results offered preclinical proof for the use of P18-PEtOx-DOPE-DOX nanoliposomes in KRT-1+ breast cancer therapy.

Unusual presentation of immunoglobulin G4-related disease: A case report.

Immunoglobulin G4-related disease (IgG4-RD) is an inflammatory disease characterized by a tumor-like infiltration of IgG4 positive plasma cells and fibrosis in various organs. The exact pathogenesis remains unknown. In this article, we discuss the diagnostic management of IgG4-RD with reference to clinical, serologic, pathological and radiological data on a 17-year-old male patient with lumbar vertebral involvement.

Real-world evaluation of "Eczema in psoriatico": Bridging the gap between dermatology and dermatopathology.

The diagnosis of psoriasis is mainly made by clinical examination but on some occasions according to the localization or duration of the lesions when spongiosis is more prominent, it can be challenging and may be considered as overlapping eczema. To evaluate the patients for "eczema in psoriatico" and to present the differences between psoriasis. Biopsy outcomes of thirty-one patients who were histologically diagnosed with psoriasis and psoriasiform dermatitis because of the erythematous and scaly plaque lesions located on hands and feet, between 2013 and 2015, were evaluated retrospectively. Histopathologic findings compatible with psoriasis and accompanied by spongiosis and spongiotic vesicles were evaluated as eczema in psoriatico and compared with psoriasis. In this study thirty-one patients, including 18 patients with eczema in psoriatico and 13 patients with psoriasis of hands and/or feet were included. Of the 31 patients, 15 (48.4%) were women and 16 (51.6%) were men, in 61.3% of cases, biopsies were taken from hands (61.1% of "eczema in psoriatico", 61.5% of psoriasis) and 38.7% from feet (38.9% of "eczema in psoriatico", 38.5% of psoriasis). There was a statistically significant difference between two groups in terms of parakeratosis severity and distribution, the presence of neutrophil and plasma in stratum corneum, the presence of granular layer loss and suprapapillar plate thinning, the shape of retes, the presence of lymphocytic exocytosis, spongiosis and spongiotic vesicles, the intensity of infiltrates in the papillar dermis and the presence of dermal edema (P < .05). Histology supports a continuum between psoriasis and eczema that share histological similarities and at the same time should be considered a separate entity, eczema in psoriatico.

Calretinin immunohistochemical staining in Hirschsprung's disease: An institutional experience.

Objective: This study aims to evaluate the results obtained by calretinin staining on tissue samples for diagnosing Hirschsprung's disease (HD) in a single institution, by single expert. Methods: A retrospective evaluation was done for calretinin immunostaining in HD patients for a period of 3 years. Calretinin staining was evaluated in nerve fibers. Calretinin immunohistochemistry was considered positive if any staining was seen in nerve fibers and/or ganglion cells in the lamina propria, muscularis mucosa or submucosa. According to staining intensity, staining was classified as strong, weak or negative. The pathological diagnosis was based on presence or absence of ganglion cells (G0/G1) and nerve hypertrophy (N0/N1). Samples were classified according to the depth (presence of submucosa or intermuscular area), the type (biopsy or resection specimen) and staining intensity of calretinin (strong, weak, or negative staining). Results: A total of 96 tissue samples from 56 patients were studied. Tissues were from colon (43.8%), rectum (43.8%), stoma (6.2%), ileum (3.1%) and appendix (3.1%). The pathological diagnosis was G0N0 in 14.6%, G1N0 in 54.2%, G0N1 in 25% and G1N1 in 6.2% of cases. Our materials consisted of 92 tissue biopsies and four resection specimens. Intermuscular layer was present in 87.5% of materials and 12.5% of biopsies contained submucosa. Calretinin staining was negative (C0) in 37.5% of cases, strong positive (C1) in 47.9%, and weak positive (C2) in 14.6%. When the C0 category was taken as the reference, the status of calretinin staining as C2 (weak positive) in cases with pathological diagnosis of G1N0 was found to be 37.575 times that of cases with G0N0 (OR [95% CI]: 37.575 [2.928, 482.176], p=0.006) and the status of calretinin staining as C1 (strong positive) in cases with pathologic diagnosis of G1N0 was found to be 131.401 times that of G0N0 (OR [95% CI]: 131.401 [9.263, 1864.082), p<0.001). Conclusion: Calretinin staining is positive whenever ganglion cells are present independent from presence of nerve hypertrophy, the depth and the site of the biopsy or staining intensity. It is negative in all aganglionic samples. Calretinin staining is a reliable ancillary test in HD diagnosis.

Germline pathogenic variant spectrum in 25 cancer susceptibility genes in Turkish breast and colorectal cancer patients and elderly controls.

Inherited pathogenic variants account for 5% to 10% of all breast cancer (BC) and colorectal cancer (CRC) cases. Here, we sought to profile the pathogenic variants in 25 cancer susceptibility genes in Turkish population. Germline pathogenic variants were screened in 732 BC patients, 189 CRC patients and 490 cancer-free elderly controls, using next-generation sequencing-based multigene panel testing and multiplex ligation-dependent probe amplification testing. Pathogenic variants were detected in 17.2% of high-risk BC patients and 26.4% of high-risk CRC patients. More than 95% of these variants were clinically actionable. BRCA1/2 and mismatch repair genes (MLH1, MSH2 and MSH6) accounted for two-thirds of all pathogenic variants detected in high-risk BC and CRC patients, respectively. Pathogenic variants in PALB2, CHEK2, ATM and TP53 were also prevalent in high-risk BC patients (4.5%). BRCA1 exons 17-18 deletion and CHEK2 c.592+3A>T were the most common variants predisposing to BC, and they are likely to be founder variants. Three frequent MUTYH pathogenic variants (c.884C>T, c.1437_1439delGGA and c.1187G>A) were responsible for all MUTYH biallelic cases (4.4% of high-risk CRC patients). The total pathogenic variant frequency was very low in controls (2.4%) and in low-risk BC (3.9%) and CRC (6.1%) patients. Our study depicts the pathogenic variant spectrum and prevalence in Turkish BC and CRC patients, guiding clinicians and health authorities for genetic testing applications and variant classification in Turkish population.

Prevalence of Helicobacter pylori among children in a training and research hospital clinic in Istanbul and comparison with Updated Sydney Classification Criteria.

OBJECTIVE: Helicobacter pylori (H. pylori) is a gram-negative bacterium and one of the reasons for gastritis, peptic and duodenal ulcers. It is a crucial public health problem for both children and adults, especially in developing countries. This study aims to investigate the prevalence of Helicobacter pylori positivity in children and to compare with updated Sydney classification criteria. METHODS: This study was conducted from January 2015 to June 2017. This study included 885 children aged 0-17 year(s). Endoscopic biopsies were evaluated for the diagnosis of infection due to H. pylori. RESULTS: The findings showed that 418 (47.2%) of 885 children were positive for H. pylori, and this positivity had a significantly increasing correlation with the presence of chronic inflammation, neutrophilic activity, lymphoid aggregates, and follicles. Erythematous pangastritis and antral nodularity on endoscopic findings had a correlation with H. pylori positivity. CONCLUSION: In this hospital-based study, the findings suggest that H. pylori infection is a problem for children and more extensive studies are needed to determine the prevalence of H. pylori positivity among children.

Evaluation of microvessel density with CD31 and CD105 in patients with psoriasis under methotrexate and acitretin therapy.

INTRODUCTION: Methotrexate and acitretin are known to be effective in the treatment of psoriasis, but the mechanisms of the effects of these drugs are not fully known. AIM: To investigate the effect of methotrexate and acitretin on microvessel density (MVD) in psoriasis. MATERIAL AND METHODS: Eighteen patients with psoriasis treated with methotrexate and 9 patients with psoriasis treated with acitretin (AT) were included in this study. MVD was evaluated immunohistochemically by using CD31 and CD105 (endoglin) antibodies. RESULTS: In the methotrexate group, the decrease in CD31 levels after treatment was found to be statistically significant, while in the AT group it was found to be highly significant. In both methotrexate and AT group, there was a statistically highly significant decrease in CD105 levels after treatment. There was no statistically significant difference between CD31 measurements of methotrexate and AT groups. When CD105 levels were measured before and after treatment, no statistically significant difference was found between methotrexate and AT. According to the results of CD31 changes before and after treatment, the CD31 difference was not statistically significant in both groups while the difference was higher in the AT group. CD105 differences were not statistically significant in both treatment groups before and after treatment. CONCLUSIONS: CD31 and CD105 dyes indicate the effects of therapies on vascular proliferation and may be indicators that can be used in daily routine and follow-up studies for psoriasis.

Desmoplastic Melanoma as a Diagnostic Pitfall.

Dear Editor, Desmoplastic melanoma (DM) is a rare histological subtype of melanoma, usually presenting as a slowly-growing, amelanotic, discoid, and/or firm lesion composed of spindle cells with abundant collagen (1). It is more common on sun-exposed areas, especially on head and neck in elderly patients (2). Regional lymph node involvement is reported to be less frequent than in other cutaneous melanomas (3). Desmoplastic melanoma can clinically mimic a wide spectrum of benign and malignant lesions, including Bowen's disease, desmoplastic nevus, basal cell carcinoma, squamous cell carcinoma, lentigo maligna, dermatofibrosarcoma protuberans, peripheral nerve sheath tumors, cysts, or hypertrophic/keloid scars (4). Regarding its appearance, at the time of diagnosis DM frequently presents as advanced lesions with deep infiltration. A 60-year-old man presented with an one-year history of an asymptomatic, erythematous, well-defined plaque in the right lumbar region (Figure 1). Dermatological examination revealed a 5×5 cm, pink/red infiltrated plaque accompanied by a 6 mm dark-brown melanocytic lesion. Dermoscopically, atypical vascular structures in the form of linear, irregular, and dotted vessels, milky-red areas, and atypical pigment network, and streaks were observed near the melanocytic lesion (Figure 2). A 4 mm punch biopsy was performed on the erythematous plaque next to the melanocytic lesion, and a dermal-based, paucicellular proliferation of atypical spindle cells without melanin in a sclerotic stroma was found histologically (Figure 3, a). Immunohistochemically, dermal spindle cells were stained with S-100 and HMB45 antibodies (Figure 3, b). The patient was histologically diagnosed with melanoma, of the desmoplastic subtype. The lesion was totally excised with 2 cm clear margins. A diagnosis of nonulcerated nodular melanoma with a Breslow thickness of 4 mm and a mitotic index 1/mm2 was established. Sentinel lymph node biopsy revealed no metastases. No systemic metastases were detected in PET-CT scanning and cranial magnetic resonance imaging. The patient remained under follow-up and has been free of any local recurrence or primary or systemic metastasis for 3 years. Dermoscopic characteristics of DM are not well known, probably due to it not being considered a melanocytic lesion. Debarbieux et al. first reported the dermoscopic features of desmoplastic melanoma in six cases (5). They found that only half of the cases presented one classical feature of a melanocytic lesion, whereas the other cases were diagnosed based on the presence of figures of regression such as white scar-like and "peppering", multiple (>4) color, and melanoma-related vascular patterns (five out of six) such as linear-irregular vessels and milky-red areas (5). In the largest DM case series, Jaime et al. reported that all DM featured at least 1 melanoma-specific structure, with atypical vascular structures being the most common (6). Similarly, in our patient dermoscopy showed an atypical pigment network and streaks, atypical vascular structures, and milky-red areas, which is predictive for melanoma. We reported this case to serve as a reminder to consider desmoplastic melanoma in the differential diagnosis of pink tumoral lesions despite its rarity and atypical localization.

Dermoscopy of stage llA mycosis fungoides.

OBJECTIVE: Differential diagnosis of mycosis fungoides (MF) in the early stages can be challenging. Dermoscopy has been reported to be useful in the evaluation of early MF. However, to our knowledge, there is no study that specifies these early stages as stage IA, IB or IIA. The present study aims to evaluate the dermoscopic findings of stage IIA MF in comparison with plaque psoriasis (PP). METHODS: Thirty-four patients aged between 16-70 years with stage IIA MF (n=17) and PP (n=17) were evaluated in this prospective study. Dermoscopic examinations were performed by manual dermatoscopy (Dermlite DL4). χ2 test was used. RESULTS: In patients with stage IIA MF, orange-yellow patches (88.2%), short, fine and linear vessels (82.3%), geometric white scales (70.5%), perifollicular white scales (47%) and white patches (35.2%) were common, while dotted vessels (94.1%), diffuse lamellar white scales (88.2%) and dotted and globular vessels (70.5%) were common in patients with PP. Although spermatozoa-like structures, purpuric dots, collarette white scales and Y-shaped arborizing vessels were common in patients with MF, this was not statistically significant. Geometric white scales (clinically; cigarette paper-like wrinkly scales) correlated with alternating parakeratosis and orthokeratosis in the stratum corneum histopathologically. CONCLUSION: A unique aspect of our study is that this study provides insights about the importance of scales in differentiating MF from PP. Orange-yellow and white patches, short, fine and linear vessels, geometric and perifollicular white scales may be useful in distinguishing stage IIA MF from PP by hand-held dermoscopy.

Superficial CD34-Positive Fibroblastic Tumor: Report of an Extremely Rare Entity.

Superficial CD34-positive fibroblastic tumor (SCPFT), a newly described neoplasm is a rare mesenchymal neoplasm of intermediate malignancy. A 63-year-old man presented with a painless, slow-growing, skin-colored nodule of 8 × 4 mm in diameter on the right side of the neck. It was completely resected. Histologically, a tumor located in the subcutis with the minimally infiltrative pattern was detected. The tumor was composed of variably enlarged bizarre and pleomorphic spindle to polygonal cells. Tumor cells were stained strongly diffuse positive with CD34 and weak positive with keratin, negative with STAT6, FLI-1, ERG, S100, desmin, and smooth muscle actin. The fluorescence in-situ hybridization (FISH) analysis was negative for COL1A1 gene rearrangement. As per the findings, the case was diagnosed as a SCPFT. It is a borderline mesenchymal neoplasm occurring within the superficial soft tissues with distinctive morphological and immunohistochemical features.

Bag-1 stimulates Bad phosphorylation through activation of Akt and Raf kinases to mediate cell survival in breast cancer.

BACKGROUND: Bag-1 (Bcl-2-associated athanogene) is a multifunctional anti-apoptotic protein frequently overexpressed in cancer. Bag-1 interacts with a variety of cellular targets including Hsp70/Hsc70 chaperones, Bcl-2, nuclear hormone receptors, Akt and Raf kinases. In this study, we investigated in detail the effects of Bag-1 on major cell survival pathways associated with breast cancer. METHODS: Using immunoblot analysis, we examined Bag-1 expression profiles in tumor and normal tissues of breast cancer patients with different receptor status. We investigated the effects of Bag-1 on cell proliferation, apoptosis, Akt and Raf kinase pathways, and Bad phosphorylation by implementing ectopic expression or knockdown of Bag-1 in MCF-7, BT-474, MDA-MB-231 and MCF-10A breast cell lines. We also tested these in tumor and normal tissues from breast cancer patients. We investigated the interactions between Bag-1, Akt and Raf kinases in cell lines and tumor tissues by co-immunoprecipitation, and their subcellular localization by immunocytochemistry and immunohistochemistry. RESULTS: We observed that Bag-1 is overexpressed in breast tumors in all molecular subtypes, i.e., regardless of their ER, PR and Her2 expression profile. Ectopic expression of Bag-1 in breast cancer cell lines results in the activation of B-Raf, C-Raf and Akt kinases, which are also upregulated in breast tumors. Bag-1 forms complexes with B-Raf, C-Raf and Akt in breast cancer cells, enhancing their phosphorylation and activation, and ultimately leading to phosphorylation of the pro-apoptotic Bad protein at Ser112 and Ser136. This causes Bad's re-localization to the nucleus, and inhibits apoptosis in favor of cell survival. CONCLUSIONS: Overall, Bad inhibition by Bag-1 through activation of Raf and Akt kinases is an effective survival and growth strategy exploited by breast cancer cells. Therefore, targeting the molecular interactions between Bag-1 and these kinases might prove an effective anticancer therapy.

Morphea secondary to interferon beta1b injection: a case and review of the literature.

Interferon beta (IFNß) is a drug used successfully in the treatment of multiple sclerosis (MS). Although IFNß is a safe and well-tolerated drug, dermatological side effects are common. The most common dermatological adverse effect is a local reaction at the injection site. It may also cause inflammatory and immune-mediated dermatological side effects. However, morphea induced by IFNß1b injection is very rare.

Dual-Inhibition of mTOR and Bcl-2 Enhances the Anti-tumor Effect of Everolimus against Renal Cell Carcinoma In Vitro and In Vivo.

Renal cell carcinoma (RCC) is the predominant type of kidney cancer. Mammalian target of rapamycin (mTOR) inhibitor everolimus is currently used as a second-line therapy for sorafenib or sunitinib-refractory metastatic RCC patients. The clinical limitation confronted during everolimus therapy is the onset of drug resistance that decreases the efficacy of the drug. Elevated level of anti-apoptotic Bcl-2 protein is proposed to be an emerging feedback loop for the acquired drug-resistance in various cancer types. In this study, the Bcl-2 inhibitor ABT-737 was used in combination with everolimus to enhance its anti-tumor effectiveness in everolimus-resistant RCC cell lines. Everolimus and ABT-737 combination synergistically led to a decrease in the proliferation of primary site A-498 and metastatic site Caki-1 RCC cell lines, which was accompanied by a reduction in protein levels of cell cycle and mTOR pathway proteins. In both RCC cell lines, everolimus-ABT-737 combination not only induced apoptosis, caspase and PARP-1 cleavage but also a decrease in Bcl-2 protein levels in parallel with a concomitant increase in Bim and Noxa levels. In order to confirm our in vitro findings, we have generated everolimus-resistant RenCa cell line (RenCares) to establish a RCC mouse xenograft model. Animals co-treated with everolimus and ABT-737 exhibited a complete suppression of tumor growth without any notable toxicity. This study thus proposes the everolimus-ABT-737 combination as a novel therapeutic strategy for the treatment of RCC to overcome the current clinical problem of everolimus resistance.

The largest epidermal cyst with vitiligo lesions following female genital mutilation: a case report and literature review.

Epidermoid vulvar cystic lesions are proliferations of epidermal cells that can occur as a complication of female genital mutilation (FGM), which is still a common practice in many cultures, especially in Africa. A 36-year-old Sudanese woman presented with an enlarged clitoral mass that had first appeared 2 years earlier. Her medical history showed that she had undergone FGM when she was 3 years old. A perineal examination revealed a mobile, nontender, rounded cystic swelling with vitiligo lesions. After the cyst was excised, it revealed a 13 ×11 × 11 cm unilocular round mass. An epidermoid cyst was reported following microscopy. Follow-up 6 months later revealed a good result with no recurrence. To date, this is the largest epidermoid cyst following FGM and the first one with vitiligo lesions reported in the literature.

Goblet cell carcinoid of the appendix accompanied by adenomatous polyp with high-grade dysplasia at the cecum.

Goblet cell carcinoid tumor of the appendix is an uncommon neoplasia that shares the histological attributes of both adenocarcinoma and carcinoid tumors. Its prognosis has a more aggressive course than the other known carcinoid tumors. Clinical diagnosis of goblet cell carcinoid is seldom made preoperatively. The most common clinical presentation of goblet cell carcinoid tumor is acute appendicitis. In this study, we report a patient on whom right hemicolectomy was performed because of a cacal sessile polyp with high grade dysplasia; goblet cell carcinoid tumor of the appendix was revealed incidentally during microscopic evaluation of the appendectomy specimen. The patient healed uneventfully and no recurrence was observed after the 12-month follow-up period. Careful microscopic examination of the appendectomy specimen is key for the diagnosis of appendiceal tumors such as goblet cell carcinoid, especially in elderly patients.