A Review and Case Study of Genital and Extragenital Human Papillomavirus Type 6 and 11 Infections in Men Who Have Sex with Men Accompanied by Human Immunodeficiency Virus Infection.

Extragenital warts caused by HPV types 6 and 11 are rarely reported. However, major risk factors for anogenital warts (AGW) include men who have sex with men (MSM) and Human Immunodeficiency Virus (HIV) infection. The incidence of extragenital warts among these populations has not been reported. This study presented a case report of a 33-year-old male with high-risk sexual behavior who showed symptoms of flesh-colored and hyperpigmentation papules. Furthermore, verrucous surfaces were observed at genital and extragenital. The patient had a history of using the same razor for pubic and armpit hair, bathing with a mesh scrub, and scratching the anal area. The histopathological result showed koilocytes, while polymerase chain reaction (PCR) examination for both genital and extragenital lesions confirmed HPV type 6 and 11. This represented the first reported case describing the incidence of extragenital and AGW caused by HPV types 6 and 11. The transmission of extragenital warts was facilitated through fomites autoinoculation, particularly in the immunocompromised condition induced by HIV, which was common among MSM. Extragenital warty-like lesions were considered as warts caused by HPV type 6/11, in HIV-infected persons, specifically MSM.

The Importance of p16 and p53 Immunohistochemical Staining in Diagnosing Vulvar Lichen Simplex Chronicus Mimicking Vulvar Intraepithelial Neoplasia with False-Positive Human Papillomavirus Type 66.

Vulvar intraepithelial neoplasia (VIN), the precursor lesion of vulvar squamous cell carcinoma (VSCC), may present as pruritic or asymptomatic lichenified plaques surrounded by single or multiple discrete or confluent macules or papules. VIN is divided into high-grade squamous intraepithelial lesion (HSIL), which is human papillomavirus (HPV)-driven, and differentiated VIN (DVIN), which develops independently of HPV. Histopathological examination and HPV genotyping polymerase chain reaction (PCR) tests should be performed to distinguish between HSIL and DVIN. Lichenified plaques surrounded by multiple papules are found not only in VIN but also in vulvar lichen simplex chronicus (LSC). This chronic inflammatory skin disease mostly appears in labia majora and is triggered by sweating, rubbing, and mental stress. IHC staining of p16 and p53 are recommended as the most commonly used biomarkers for VIN in diagnostically challenging cases. IHC staining is also beneficial to confirm the accuracy of the HPV detection technique, as p16-negative staining may also represent a false-positive result. We report a case of the importance of p16 and p53 IHC staining in diagnosing vulvar LSC mimicking VIN with false-positive HPV-66. The patient was previously diagnosed with VIN based on clinical examination. HPV-66 was detected by PCR from a vulvar biopsy sample. Histopathological examination revealed stromal lymphocytic infiltration with non-specific chronic dermatitis; neither atypia nor koilocyte was observed. Both p16 and p53 IHC staining were negative. The patient was diagnosed and treated as vulvar LSC with 10 mg cetirizine tablet, emollient, and 0.1% mometasone furoate cream. Clinical improvement was observed as the lesions became asymptomatic hyperpigmented macules in the 4 weeks of follow-up, without recurrence after 3 years of follow-up. Both p16 and p53 IHC staining might help distinguish HSIL and DVIN mutually and from other vulvar mimics in diagnostically challenging cases.

Generalized Asymptomatic Nodulo-Ulcerative Lesions Without Systemic Symptoms in a Secondary Syphilis Patient Co-Infected with HIV.

Syphilis is a sexually-transmitted disease with various clinical stages. Secondary syphilis manifestations may mimic other skin lesions. Patient co-infected with Human Immunodeficiency Virus (HIV), with CD4 cell counts of 200-499 cells/mm3, often manifests an atypical cutaneous lesion, which may also occur as nodular or ulcerative lesions. Generalized nodulo-ulcerative lesions without systemic symptoms in secondary syphilis patients with HIV co-infection are rarely reported. A 22-year-old man presented with generalized asymptomatic multiple erythematous papules and plaques with scales, as well as nodular and nodulo-ulcerative lesions on the trunk, both arms, and both legs. His lesions spread progressively without the presence of any prodromal symptoms or adenopathy. He was previously diagnosed with HIV and is currently on antiretroviral medications, with a CD4 cell count of 388 cells/µL. His venereal disease research laboratories (VDRL) result was reactive (titer of 1:256). His Treponema pallidum hemagglutination assay (TPHA) result was also reactive (titer of 1:10,240). A skin biopsy was performed from the nodulo-ulcerative lesion on his back. Hematoxylin-eosin staining revealed a hyperplastic epidermis, a massive influx of plasma cells, and lymphocyte infiltration into the deep dermis, especially in the peri-adnexal, peri-vascular, and peri-muscular regions. The patient was diagnosed with secondary syphilis with HIV co-infection. He had no previous history of drug allergy. A single dose of 2.4 million units of benzathine penicillin G was administered. Almost all the lesions became hyperpigmented macules after two weeks and resolved completely after one month. His VDRL titer declined to 1:32 after three months. The various atypical lesions of secondary syphilis may lead to misdiagnosis and delayed treatment. The presence of multiple asymptomatic nodulo-ulcerative lesion without prodromal symptoms may indicate the presence of secondary syphilis, notably in patients co-infected with HIV. Therefore, knowledge of atypical cutaneous manifestations of secondary syphilis is warranted in order to treat patients accordingly.

A Case of Genital and Extragenital Warts Unresponsive to Immunotherapy Using Measles, Mumps, Rubella Vaccine.

Anogenital warts (AGWs) are globally recognized as the most common sexually transmitted infections (STIs) caused by the human papillomavirus (HPV), particularly types 6 and 11. Meanwhile, immunotherapy is one of the treatments of choice for patients with extensive AGWs. Measles, mumps, and rubella (MMR) vaccine induce the production of various T helper 1 cytokines to elicit immune responses, resulting in the clearance of both treated and untreated warts. This study reported a case of extensive genital and extragenital warts in a 53-year-old male which had occurred for five years, with no pseudo-Koebner phenomenon. The history of MMR vaccination was uncertain but the patient received oral antibiotics for one week, one month before seeking consultation. Physical examination showed extensive verrucous and hyperkeratotic papules, plaques, and nodules in the lower abdomen, pubic, inguinal, genital, and gluteal regions. Acetowhite test results were positive, while polymerase chain reaction (PCR) results were positive for HPV types 6 and 11. The patient received an intralesional injection of 0.5 mL MMR vaccine into the largest warts with a 3-week interval. However, during the one-month follow-up after the third injection, no improvement was observed in either the size or number of warts. Based on the results, several factors must be considered to determine the best candidate for immunotherapy, particularly with MMR vaccine, to achieve an optimal outcome. These factors include the active state of diseases, duration of diseases, as well as a history of sensitization, and broad-spectrum antibiotics.

Effectiveness of Pulsed Dye Laser Treatment in Tufted Angioma: A Promising Intervention.

Introduction: Tufted angioma (TA) is a rare benign vascular tumor usually occurring in the first year of life. It may present as reddish papules or purplish red to black plaques. Tender lesions commonly affect the neck, upper trunk, and shoulders. Histologic tufts of capillaries infiltrating the dermis in a "cannon ball" distribution pattern confirm the diagnosis. However, effective treatments for TA are scarce. Pulsed dye laser (PDL) is an alternative therapy for TA, particularly concerning cosmetics and pain relief. This case report demonstrates the effectiveness of PDL as a treatment for TA. Case: We report a 15-year-old girl with five-year history of painful purplish red plaques on her left cheek, neck, chest, left shoulder, and back. Histopathological examination from skin biopsy showed discrete "cannon ball" pattern in the dermis. Laboratory examination revealed normal platelet count and fibrinogen level. Based on these presentations, the diagnosis of TA without complications was made. We treated the lesion using 595-nm PDL with 6.5-10 J/cm2 fluence of, 1.5 ms pulsed duration, and 5-7 mm spot size every three weeks. Reductions in redness and pain were seen after four sessions of treatment. Discussion: PDL promotes selective vascular damage with minimal injury to the surrounding skin. Capillary tufts in TA could therefore serve as a target for laser treatment, which may result in fading redness and pain reduction. Conclusion: PDL is effective in reducing redness and pain in TA.

Molluscum Contagiosum in HIV Patient Treated with 20% Topical Glycolic Acid After Resistance with Topical Tretinoin.

Molluscum contagiosum (MC) is a benign papular skin infection caused by Molluscum contagiosum virus (MCV). Over the past 30 years, the incidence of MK has continued to increased association with sexually transmitted infections and human immunodeficiency virus (HIV) infection. The incidence of MC in HIV patients is quite high at 5-8%. Until now there is no standard therapy used for the treatment of MC in patients with HIV. In HIV patients, anti retro viral therapy (ARV) is the main therapy with several other additional therapies such as cantaridin, chemical peeling agents such as glycolic acid (20-70%) and trichloroacetic acid (20-100%), cryosurgery, electrosurgery, incision, lactic acid, laser surgery, podophyllin, retinoic acid, and urea. There have been no studies regarding the administration of topical 20% glycolic acid in MC patients. We report a case of MC in an HIV patient who was treated with 20% topical glycolic acid after failing treatment with topical tretinoin. The diagnosis was made clinically, cytologically, and histopathologically, a white mass was found on compression of the lesion and Henderson-Paterson bodies. The lesions on the face, arms, and legs were given glycolic acid lotion 20% which was applied once a day at night. The lesions started to show responses to the treatment at week 6th as some of the MC papules became hyperpigmented macules. The side effects of therapy that appeared were itching and hyperpigmentation. Topical 20% glycolic acid can be used for MC therapy with minimal side effects, easy to apply and safe.

Generalized Reddish Skin Nodules.

Diagnosis of nodular red lesions is challenging. The differential diagnosis includes dermal nevus, angioma, pyogenic granuloma, amelanotic melanoma, eccrine poroma, Kaposi's sarcoma, skin malignancy or metastasis. Erythema nodosum is one of the common consideration of the red skin nodules, however fully work up should be done to find the right diagnosis.A 60 years old female admitted to our hospital due to pain dark reddish skin nodules since one month. She had continuously high grade fever of 39 Celsius accompanied by arthralgia and fatigue since two months prior to admission and she lost 6 kg of weight in 2 months. On admission, physical examination revealed slight fever, pale conjunctiva, mild hepatosplenomegaly, tender dark red nodules 0.3 to 2 cm, firm edge, at her cheek, abdominal area and both lower extremities. No lymph nodes enlargement was noticed. Her laboratory test showed haemoglobin 9,1 g/dl, WBC 3,040/mL, PLT 149,000/mL, SGOT 48 U/L, SGPT 43 U/L, urea 12.5 mg/dL, creatinine 0.67 mg/dL. She was found to be non-reactive for HBsAg, HCV, and HIV antigens. Urine routine and microscopic examination was unremarkable.Her histopathology of left foot nodule biopsy revealed cutaneous lymphoma. The immunohistochemical (IHC) stain of CD45, CD20, and CD10 were positive, Ki67 were also positive  with >70% tumor cells, while CD3,CD56, CD30, and Granzyme were negative. Her final diagnosed was Cutaneous Diffuse large B cell lymphoma.Primary cutaneous lymphomas of B-cells occur less frequently than primary cutaneous T-cells lymphomas. Primary extra-nodal diffuse large B-Cell lymphoma (DLBCL) can be seen in up to 40% of cases. However skin involvement is less common and in a large cohort of DLBCL cases, skin involvement at presentation was seen only in 3.3% of cases.It characterized by few lesions, in general showing nodules or infiltrations of relatively fast growth and have no itching. The diagnosis is made by the immunohistochemical findings, clinicopathological correlation, and molecular pathology.  The lymphomas have different clinical behaviours despite being identical in morphological appearance. The primary lymphomas presents with local recurrence in up to 68% of the cases and with rare extra-cutaneous dissemination, with an average rate of 5-year survival varying from 89 to 96%. Cutaneous lymphoma should be always become one of considered diagnosed of skin red nodules even it is rare.

Sporadic renal cell carcinoma with widespread metastasis in young patient: A rare case report.

Renal cell carcinoma occurrence is increasing from time to time and known as one of the most common cancers worldwide. RCC usually found in older age and common acquired risk factors for RCC including obesity, hypertension, diabetes, smoking and long-term use of NSAIDs. As for genetic risk, it is noted that Von Hippel-Lindau gene involved in the pathogenesis of RCC. Many treatment strategies were developed for RCC with various outcome. Here, we present a sporadic clear cell renal carcinoma in young male without VHL gene mutation and survive for long term period despite progressivity of treatment.

CD103+ T Lymphocyte Count Linked to the Thickness of Invasion on Acral Melanoma without E-Cadherin Involvement.

BACKGROUND: Acral melanoma (AM) is a malignancy that originates from melanocytes, located in an anatomical area without sun exposure, aggressive, resistant to chemotherapy, and quickly metastasize. The invasion capability of tumor cells is the main factor for metastasis in malignancy. E-cadherin is a marker of tumor progressivity that has an important role in the process of invasion. The responsibility of E-cadherin in the invasion process of AM is not well known. CD103 is an immune component found in the tumor microenvironment that contributes to melanoma progression control, whereas E-cadherin is the ligand for CD103. PURPOSE: The objective of this research was to see if there was an association between E-cadherin and CD103 immunoexpression and the thickness of invasion in AM. MATERIALS AND METHODS: This is observational cross-sectional research. Formalin-fixed paraffin-embedded (FFPE) acral melanoma tissue samples were collected during 2014-2020 at the Department of Anatomic Pathology, Dr. Hasan Sadikin Hospital, Bandung. A total of 40 samples were collected, including 20 cases of invasive melanoma less than 4 mm thickness and 20 cases of invasive melanoma greater than 4 mm thickness. All samples were immunostained with E-cadherin and CD103. Chi-Square test was used to examine the association concerning E-cadherin and CD103 with the thickness of invasion, respectively. The p-value of 0.05 was chosen as the significance level. RESULTS: This study showed an insignificant association between E-cadherin immunoexpression and the thickness of invasion on AM (p = 0.4272). CD103 immunoexpression had a significant association with the thickness of invasion on AM (p = 0.0001). CONCLUSION: The findings revealed that CD103 in AM is associated with the thickness of invasion, and it may play important functions throughout the invasion process despite the uninvolvement of E-cadherin.

The Ethanol Extract of Marine Sponge Aaptos suberitoides Suppress Cell Viability, Cell Proliferation and Cell Migration in HER2-Positive Breast Cancer Cell Line.

OBJECTIVE: This study aimed to investigate the cytotoxicity, anti-proliferation and anti-migration effect of the ethanol extract of Aaptos suberitoides on trastuzumab-resistant HER2+ breast cancer cell line. METHODS: Aaptos suberitoides was collected from Tinjil Island, Banten, Indonesia, and was processed with maceration and ethanol extraction. HCC-1954 cells were treated with the ethanol extract and then followed by 3- [4, 5-dimethylthiazol-2-yl] -2.5 diphenyl tetrazolium bromide (MTT) assay to assess cytotoxicity, clonogenic assay and three-dimensional (3D) spheroid assay to evaluate anti-proliferative effect in two-dimensional and 3D model, respectively, and wound healing assay to determine anti-cell migration effect. Four parametric regression was used to analyse the IC50. RESULTS: This study revealed that the ethanol extract of Aaptos suberitoides suppressed cell viability in correlation with cell death induction. The IC50 values of the ethanol extract of Aaptos suberitoides using MTT assay and clonogenic assay were 12.0 ppm and 4.36 ppm, respectively. The extract demonstrated an inhibition effect on spheroid growth. In low concentration, the extract of Aaptos suberitoides inhibited cell migration. Furthermore, MS analysis showed that the most abundant compounds in this extract has molecular weight m/z 229.81 [M+H]+. CONCLUSION: This study revealed that the ethanol extract of Aaptos suberitoides demonstrates cytotoxicity, anti-proliferation and anti-migration effect as well as inhibition effect on three-dimensional spheroid growth in trastuzumab-resistant HER2+ breast cancer cell line.
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The Major Role of NF-κB in the Depth of Invasion on Acral Melanoma by Decreasing CD8+ T Cells.

BACKGROUND: The tumor microenvironment including immune surveillance affects malignant melanoma (MM) behavior. Nuclear factor κB (NF-κB) stimulates the transcription of various genes in the nucleus and plays a role in the inflammatory process and in tumorigenesis. CD8+ T cells have cytotoxic properties important in the elimination of tumors. However, inhibitory receptors on the cell surface will bind to programmed death-ligand 1 (PD-L1), causing CD8+ T cells to lose their ability to initiate an immune response. This study analyzed the association of NF-κB and PD-L1 expression levels and CD8+ T-cell counts with depth of invasion of acral MM, which may be a predictor of aggressiveness related to an increased risk of metastasis. METHODS: A retrospective cross-sectional study was conducted in the Department of Anatomical Pathology, Faculty of Medicine, Universitas Padjadjaran/Hasan Sadikin Hospital using 96 cases of acral melanoma. Immunohistochemical staining was performed on paraffin blocks using anti-NF-κB, -PD-L1, and -CD8 antibodies and invasion depth was measured using dotSlide-imaging software. RESULTS: The study showed significant associations between the individual expression of NF-κB and PD-L1 and CD8+ T-cell number, with MM invasion depth. NF-κB was found to be a confounding variable of CD8+ T-cell number (p < .05), but not for PD-L1 expression (p = .154). Through multivariate analysis it was found that NF-κB had the greatest association with the depth of invasion (p < .001), whereas PD-L1 was unrelated to the depth of invasion because it depends on the number of CD8+ T cells (p = .870). CONCLUSIONS: NF-κB plays a major role in acral MM invasion, by decreasing the number of CD8+ T cells in acral MM.