Evaluation of peritumoral inflammatory infiltration and its relationship with different prognostic factors in cutaneous squamous cell carcinoma.

BACKGROUND: Cutaneous squamous cell carcinoma (cSCC) is one of the most common skin cancers. Prognostic factors, such as tumor thickness, play a crucial role in the management of these patients. Peritumoral inflammatory infiltration has been shown to influence the prognosis of malignancies. This study aimed to determine different prognostic factors and investigate peritumoral inflammatory infiltration in patients with cSCC. METHODS: The study population consisted of 272 patients with a diagnosis of cSCC. Clinical data, such as age and tumor location, were extracted from pathology reports, and other information was gathered by contacting the patients via phone calls. All pathology slides were reviewed by an expert dermatopathologist, and the histopathological features and prognostic factors were evaluated. RESULTS: The highest number of tumors was found in the scalp and forehead (21.3%), while the lowest number was found in the trunk and thighs (3.31%). The highest mean tumor thickness was observed in the group with no inflammatory cells; on the other hand, the lowest tumor thickness was found in the group of lymphocytes and plasma cells. The group with severe eosinophilic infiltration had the highest mean tumor thickness, while the group with no eosinophilic infiltration had the lowest mean tumor thickness. CONCLUSION: Depending on the type of peritumoral inflammatory cells, the prognosis of cSCC may be predictable.

Tissue Extract from Brittle Star Undergoing Arm Regeneration Promotes Wound Healing in Rat.

This study set out to evaluate the wound healing properties of brittle star extracts in vitro and in vivo. Due to the great arm regeneration potential of the brittle star, Ophiocoma cynthiae, the present study aimed to evaluate the wound healing effect of hydroalcoholic extracts of brittle star undergoing arm regeneration in wound healing models. The brittle star samples were collected from Nayband Bay, Bushehr, Iran. After wound induction in the arm of brittle stars, hydroalcoholic extracts relating to different times of arm regeneration were prepared. The GC-MS analysis, in vitro MTT cell viability and cell migration, Western blot, and computational analysis tests were performed. Based on the in vitro findings, two BSEs were chosen for in vivo testing. Macroscopic, histopathological and biochemical evaluations were performed after treatments. The results showed positive proliferative effects of BSEs. Specifically, forty-two compounds were detected in all groups of BSEs using GC-MS analysis, and their biological activities were assessed. The MTT assay showed that the 14 d BSE had a higher proliferative effect on HFF cells than 7 d BSE. The cell migration assay showed that the wound area in 7 d and 14 d BSEs was significantly lower than in the control group. Western blot analysis demonstrated an increase in the expression of proliferation-related proteins. Upon the computational analysis, a strong affinity of some compounds with proteins was observed. The in vivo analysis showed that the evaluation of wound changes and the percentage of wound healing in cell migration assay in the 7 d BSE group was better than in the other groups. Histopathological scores of the 7 d BSE and 14 d BSE groups were significantly higher than in the other groups. In conclusion, the hydroalcoholic extract of O. cynthiae undergoing arm regeneration after 7 and 14 days promoted the wound healing process in the cell and rat skin wound healing model due to their proliferative and migratory biological activity.

Re-evaluation of Negative Cone Biopsy Results with Ki-67 and p16 Immunostaining following Positive Cervical Biopsy.

BACKGROUND: Cervical conization is a standard diagnostic method for precancerous lesions. However, its results could be negative despite an initially positive punch biopsy. The present study aimed to re-evaluate pathological biopsies with Ki-67 and p16 immunostaining to assess the diagnostic accuracy of punch biopsies. METHODS: This retrospective study performed in Motahhari Clinic and Shahid Faghihi Hospital, (Shiraz, Iran). 88 punch and cone biopsy slides from 2007-2016 were re-evaluated by two pathologists, and the results were compared with the original diagnoses. Agreement between the initial diagnoses and re-evaluations and between our pathologists were assessed with the kappa coefficient. Twenty-two negative conization results after positive punch biopsy were re-sectioned and evaluated with Ki-67 and p16 immunostaining. RESULTS: The overall agreement (kappa) between the primary punch diagnoses by the original pathologists and those made in the present study (by the first and second pathologists) before immunohistochemical (IHC) staining was 0.33 and 0.43, respectively. The kappa coefficient between punch biopsy diagnoses by the first and second pathologists before IHC staining was 0.73, while it increased to one after IHC staining with Ki-67 and p16. Out of the 22 specimens with the positive punch and negative cone biopsies on initial diagnosis, cervical intraepithelial neoplasia (CIN) was not confirmed in 11 specimens by our pathologists after IHC staining with Ki-67 and p16. These cases were reclassified as transitional metaplasia or acute/chronic cervicitis. CONCLUSION: Punch biopsy can be misdiagnosed as CIN positive, leading to unnecessary conization. The use of Ki-67 and p16 markers as appropriate ancillary tests are recommended.

Amyloidosis cutis dyschromica: report of 3 cases.

Amyloidosis cutis dyschromica (ACD) is a rare pigmentary disorder with about 50 cases having been reported in the English literature. Only one case of ACD has been reported from Iran. We present three patients who presented with generalized hyper- and hypopigmented patches, sparing face, hands, and feet in all three cases. The presence of amorphous eosinophilic deposits in the papillary dermis confirmed the diagnosis of ACD; the deposits were stained by crystal violet in the histopathological examination of the lesions. In all three cases, similar lesions were present in some of the family members. ACD should be considered in the differential diagnosis of diffuse hyperpigmentation studded with hypopigmentation, especially when beginning in childhood.

Eosinophilic pustular folliculitis with labial and oral involvement: report of a rare presentation.

Eosinophilic pustular folliculitis (EPF) is a recurrent inflammatory dermatosis primarily involving hair follicles. Several subtypes of EPF have been described: Classic EPF, infantile EPF, and immunosuppression-associated EPF. Although classic EPF has a predilection for face, involvement of hairless areas such as palms and soles has been reported frequently. There are rare case reports of mucosal EPF. Herein, we report a woman who presented with classic EPF involving the lip and oral mucosa.

Comparison of c-Kit expression between primary and metastatic melanoma of skin and mucosa.

BACKGROUND: Melanoma causes the greatest morbidity and mortality of all skin cancers. Mucosal melanoma is a rare but highly aggressive neoplasm. According to previous studies the prevalence of KIT mutations in acral lentiginous and mucosal melanomas is relatively low (less than 15-20%), but it can have profound therapeutic implications for localized high risk or metastatic diseases. Our goal was to evaluate c-Kit expression in different types of primary and metastatic melanoma to discriminate potential candidates for targeted therapy. METHODS: We designed a cross-sectional study and selected 50 cases of malignant melanoma (primary, metastatic cutaneous, and mucosal) from the affiliated hospitals of Shiraz University of Medical Sciences in the period of 2008 to 2012. Immunohistochemistry for KIT expression was performed. Multistage sampling method was selected for sampling and chi-square test was used for statistical analysis. RESULTS: In our study, male to female ratio was 1.77. The male sex was correlated with higher tumor stage (p< 0.05). 62% (n= 31) of cases showed at least 5% of KIT-positive cells, consist of 18% (n= 9) with 5-50%, 16% (n= 8) with 51-95%, and 28% (n= 14) of cases showed more than 95% of cells expressing KIT. But in 38% (n= 19) of cases KIT expression was less than 5% of positive cells. Tumor stage was positively correlated with tumor cell immunoreactivity and intensity (p< 0.05). Metastatic melanoma showed lower percentage (43%) of positivity. Intensity of staining and percentage of positive cells were positively correlated (p< 0.001). CONCLUSION: In primary melanomas, significant KIT expression was found by immunohistochemistry, which may be useful to screen the patients for advising to KIT mutation analysis and targeted therapy.

Extragonadal sclerosing stromal tumor: a rare case report.

Sclerosing stromal tumor is a rare, benign, sex cord stromal tumor of the ovary. We report a case of extragonadal sclerosing stromal tumor in a 45-year-old woman who presented with menstrual irregularity and vague pelvic pain. Imaging studies showed a well-defined mass between the posterior wall of the bladder and uterus, suspected of being a pedunculated leiomyoma. The histopathological and immunohistochemical study was consistent with sclerosing stromal tumor. No ovarian tissue was found on representative sectioning. This is the first case of sclerosing stromal tumor in an extragonadal location.

Adenoid Cystic Carcinoma of Bartholin's Gland Clinically Mimics Endometriosis, A Case Report.

Adenoid cystic carcinoma of Bartholin's gland is a rare malignant tumor of female genital tract. We report a case of a 42-year-old woman, presenting a palpable painful mass and burning sensation on the left side of vulva during the preceding two months. Based on examination, a solid fixed painful nodule with intact mucosa was palpated on the left side of the vagina. Histological features were compatible with adenoid cystic carcinoma. Often, such lesion is clinically misdiagnosed as a cyst or inflammation. The present case was carried out with an impression of endometriosis. The possibility of cancer should be considered in any female older than 40 years of age with a lesion near the Bartholin's glands.

Hair removal laser-induced Fox-Fordyce disease emerging on the axillary and pubic areas: Report of a case and review of literature.

Key Clinical Message: Fox-Fordyce disease is a recognized adverse effect of depilating lasers. It should be considered among the differential diagnoses of the pruritic perifollicular papules that occur at the hair removal laser treatment site, including Alex/Diode laser. Abstract: Fox-Fordyce disease (FFD) is an uncommon skin disorder affecting the apocrine sweat glands and presents as pruritic skin-colored papules, mainly on the axillary and pubic areas. Some predisposing factors are proposed, including hormonal changes. A few cases of FFD have been reported after hair removal by light- and laser-assisted devices. Herein, we report FFD in some areas (axillary and pubic areas) treated with Alex/Diode hair removal laser.

Evaluation of Ki67, p16 and CK17 Markers in Differentiating Cervical Intraepithelial Neoplasia and Benign Lesions.

BACKGROUND: Cervical intraepithelial neoplasia (CIN) is a premalignant lesion capable of progressing to cervical cancer. Despite the existing well-defined criteria, the histomorphologic diagnosis is subject to high rates of discordance among pathologists. The aim of this study was to evaluate Ki-67 (MIB-1), CK17 and p16 (INK4a) (p16) markers by immunohistochemical methods in differentiating CIN from benign cervical lesions. METHODS: The present study reviewed and re-classified 77 cervical biopsies, originally diagnosed as 31 non-CIN, and 46 CIN, as 54 non-CIN, and 23 CIN based on at least two similar diagnoses. Immunostaining by Ki67, p16 and CK17 markers was performed on all cases and the results were compared with pervious and consensus diagnosis. RESULTS: The overall agreement between pervious and consensus diagnosis was 67.5% (Kappa=0.39, P<0.001). The sensitivity and specificity of Ki67 immunostaining were 95.6% and 85.1% respectively, while for p16 the corresponding values were 91.3% and 98.1%. The overall agreement, for both p16 and Ki67, with consensus diagnosis were significant (P<0.001). The sensitivity and specificity of CK17 negative staining in CIN detection were 39.1% and 40.7% respectively. CONCLUSION: Ki67 and p16 markers are recommended as complementary tests for differentiating between dysplastic and non-dysplastic lesions. CK17 does not discriminate between immature metaplasia with and without dysplasia.

Value of CD10 Expression in Differentiating Cutaneous Basal from Squamous Cell Carcinomas and Basal Cell Carcinoma from Trichoepithelioma.

BACKGROUND: In addition to the well-defined histological criteria for squamous cell carcinoma (SCC) and basal cell carcinoma (BCC), immunohistochemical techniques can be used in difficult cases for their differentiation. As differential diagnosis between trichoepithelioma (TE) and BCC is sometimes difficult for the clinician and the pathologist, CD10 may be a useful marker for definite diagnosis. We aimed to evaluate the usefulness of this marker in the differentiation between SCC and BCC and also in the differentiation between BCC and TE. METHODS: Fifty-five BCC cases, 50 SCC cases, and 20 cases of benign adnexal tumor with follicular differentiation were retrieved from the archives of the pathology departments of hospitals affiliated with Shiraz University of Medical Sciences. Immunohistochemistry for CD10 was performed on the sections obtained from formalin-fixed, paraffin-embedded blocks. CD10 immunoreactivity in the stroma and/or tumor cells was determined as follows: negative (0); 1+(10-50% positive cells); and 2+(>50% positive cells). RESULTS: Comparison of CD10 expression between the BCC and SCC groups showed a significant difference (P<0.001) in each of the tumor and stromal cells. Comparison of CD10 expression between the BCC and TE groups demonstrated a significant difference in both the tumor and stromal cells (P<0.001). There was no significant difference in CD10 expression between the stromal and tumor cells of the BCC subtypes. CONCLUSION: CD10 is a useful adjunct marker in distinguishing TE from BCC. CD10 is suggested to be one of the useful immunohistochemical markers to differentiate BCC from SCC.

Clinicopathologic evaluation of granuloma annulare: Study of 136 Iranian cases, south of Iran.

Background and Objectives: Granuloma annulare (GA) is a benign skin disorder with various histopathologic features that are rarely investigated in Iranian population. We performed this study to find out the clinical and histopathologic features of GA in our referral centre. Methods: One hundred-thirty-six patients with biopsy-proven GA were reviewed. Clinical data and pathological features were recorded. Results: One hundred-eight female patients and 28 male patients (Female/male ratio: 3.85) with mean age of 42.54 ± 21.2 years (range: 2-83 years) were recruited. Eighty-eight (64.7%) patients had interstitial infiltrative pattern and 48 (35.3%) patients had complete palisading granulomas. The infiltrate occupied both upper and lower dermis in most of the cases (67.7%). Significant mucin was detected more commonly in complete GA compared to interstitial GA (p = 0.019), but inflammation degree, eosinophils, plasma cells, and giant cells were not different between two subtypes of GA (p > 0.05). The significant inflammation contained more significant plasma cells (p = 0.006). The significantly more giant cells were detected in patients between 20 and 60 years of age (p = 0.015); but other factors were not different between age groups. Conclusions: In our study, the prevalence of GA in women was significantly higher than in men. Interstitial GA was the more common histological subtype and the inflammation was less severe and the infiltrate was mostly pandermal in our cases. More severe inflammation contained more plasma cells, and more dense giant cells were seen in middle aged patients.

Isolated Langerhans Cell Histiocytosis of the Vulva in a 28-Year-Old Lady: A Report of a Case and Brief Review of the Literature.

Langerhans cell histiocytosis (LCH) is a rare, proliferative disorder of Langerhans' cells. The presentation can vary from single organ involvement to multisystem and disseminated in severe cases, affecting children more than adults. Isolated vulvar involvement of LCH in a 28-year-old woman has rarely been described and also there are limited data for diagnosis and treatment. Herein, we report the case of a 28-year-old woman with isolated vulvar LCH, misdiagnosed with herpes simplex infection, successfully treated with thalidomide.

The effect of hydroalcoholic extract of Psidium guajava L. on experimentally induced oral mucosal wound in rat.

BACKGROUND: The aim of this study was to evaluate the biological effects of hydroalcoholic extract of Psidium guajava L leaves and phenytoin as a standard agent on the induced oral mucosal wound. METHODS: Hundred seventy Sprague Dawley rats were grouped in 5 clusters randomly. Oral mucosal wounds were induced in all rats except for the control group. Phenytoin and guajava leaf extract were used as a mouthwash. Twelve rats from the 5 groups were euthanized on day 7th and 10th, and 10 rats from each group were sacrificed on the 14th day. Interleukin-6 and total antioxidant capacity were determined in the serum. The tissues were evaluated for pathological and stereological assessments. Phytochemical analyses were performed on the hydroalcoholic extract of Psidium guajava L to determine the antioxidant potency. RESULTS: Total phenolic content test and DPPH analysis demonstrated the high potential of antioxidant capacity of Psidium guajava L. Decreasing IL-6 and increasing TAC were seen in the guajava hydroalcoholic extract and phenytoin groups. The difference of IL-6 between the wound treated guajava group and the wounded group was significant. The wound treated guajava group and wound treated phenytoin group on the 14th day increased the number of fibroblast cells and volume density of sub-mucosae effectively to the same thickness to be considered as a healed sub-mucosae layer. The volume density of the epithelium changes showed statistically significant different responses based on gender. CONCLUSION: In conclusion, hydroalcoholic extract of Psidium guajava L leaves might exert theraputic effects on oral mucositis.

Association of Non-Melanoma Skin Cancer with Temperament from the Perspective of Traditional Persian Medicine: A Case-Control Study.

Background: Non-melanoma skin cancer (NMSC) is the most common type of cancer in the world. In traditional Persian medicine (TPM), various types of temperament (Mizaj) are considered to diagnose, treat, and prevent a variety of illnesses. The present study aimed to evaluate the temperament of patients with NMSC in comparison with a control group. Methods: A case-control study was conducted in 2018 at the Dermatology Clinic of Shahid Faghihi Hospital affiliated with Shiraz University of Medical Sciences (Shiraz, Iran). A total of 110 patients, aged ≥20 years with confirmed NMSC (case group), and 181 individuals without NMSC (control group) were enrolled in the study. The temperament of the participants in both groups was evaluated using Mojahedi's Mizaj questionnaire. The data were analyzed using SPSS software, and P<0.05 was considered statistically significant. Results: The results showed that the odds ratio of developing NMSC was 2.62 (95%CI: 1.42-4.83, P=0.002) times higher in individuals with dry temperament than other types of temperament. Moreover, the odds ratio of patients with a history of chronic skin ulcers and other types of cancer was 35.7 (95%CI: 11.9-107.15, P<0.001) and 5.22 (95%CI: 1.43-19.06, P=0.012) times higher, respectively, than the control group. Conclusion: Temperament is associated with NMSC, particularly the dry temperament type, and should be considered a risk factor.

Cutaneous pseudolymphoma: A clinicopathological study and immunohistochemical patterns.

BACKGROUND: Cutaneous pseudolymphoma can histologically and clinically simulate various types of cutaneous lymphoma. We conducted the current study to evaluate the clinicopathological and immunohistochemical (IHC) aspects of cutaneous pseudolymphoma (PSL). METHODS: 30 cases of cutaneous PSL were selected from the archives of 2013-2017 in Shahid Faghihi Hospital pathology lab, Shiraz University of Medical Sciences. Available clinical data, histopathological features and IHC findings were statistically analyzed. RESULTS: The female: male ratio was 2:1 and the median age was 47±14.9 years. The lesions were located on the head and neck 26 (86.7%), trunk 2 (6.7%) and extremities 2 (6.7%). 23 (76.7%) cases had nodular pattern, while 7 (23.3%) showed diffuse pattern. The grenz zone was seen in 24 (80%) cases. Sixteen (53.3%) cases showed top heavy infiltration, 11 (36.7%) showed the same distribution of infiltration at the superficial and deep dermis, often involving the subcutaneous fat and 3(10%) showed bottom heavy infiltration. In IHC, 11(36.6%) cases showed the B cell type, 10 (33.3%) T cell type and 9 (30%) mixed type (B and T cells). CONCLUSION: None of the cases was suspicious for cutaneous lymphoma, applying IHC staining. Gender distribution, and the site of cutaneous lesions were similar to previous studies. The most common histological subtype was nodular, while the B-cell cutaneous pseudolymphoma was slightly more common compared to the T-cell type.

BRAF Mutation Analysis in Primary Acral Melanoma of 41 Cases from South of Iran.

BACKGROUND & OBJECTIVE: Acral melanoma (AM) is a common type of cutaneous melanoma that occurs in the skin of the palms, soles, and nail beds. This malignancy, like other types of cancer, has different genetic alterations. To date, despite decades of research the roles of oncogenic BRAF mutations in the pathogenesis of AM has not been fully clarified. The present study was designed to identify V600E mutation in patients with AM from the south of Iran. METHODS: The samples were collected from the pathology lab archive of Shiraz University of Medical Sciences (2015-2020). A total of 41 patients with primary invasive AM underwent excisional biopsy or amputation were collected to evaluate BRAF V600E mutation using Polymerase Chain Reaction (PCR) and Sanger sequencing. RESULTS: Total number of 41cases (21 male and 20 female) and age range of 34-87 years were enrolled. The histological subtypes were 24 acral lentiginous melanomas (ALM), 10 cases of nodular melanoma (NM), and 7 cases of superficial spreading melanoma (SSM). In our study, only one case (a 44-year-old male with nail bed AM and the histological subtype of acral lentigenous melanoma) showed BRAF-V600E mutation. CONCLUSION: These findings suggest that the population of our interest showed a very low prevalence of this mutation providing novel insights into the pathobiology of AM and its related treatment.

Cutaneous Pseudolymphoma As a Rare Adverse Effect of Medicinal Leech Therapy: A Case Report and Review of the Literature.

Hirudotherapy (leech therapy) is one of the oldest practices in medical history, and nowadays it is used for several purposes in medicine. Salvage of flaps, wound healing, pain management, and treatment of varicose veins are among the common therapeutic applications of leeches. Complications associated with leech therapy include infections, bleeding, anemia, and allergic reaction. Cutaneous pseudolymphoma (benign proliferation of lymphoid cells in the skin) follows several underlying conditions. Although persistent arthropod bite reaction is one of the conditions associated with cutaneous pseudolymphoma, it has been rarely reported after medicinal leech therapy. Here we describe the case of a patient who presented with cutaneous pseudolymphoma after leech therapy as a rare cutaneous complication of hirudotherapy.

Evaluation of treatment results and prognostic factors of uterine sarcoma: A single-center experience.

BACKGROUND: Uterine sarcomas (US) constitute a rare heterogeneous group of gynecological malignancies with aggressive characteristics and poor prognosis. Identifying the histopathological factors that determine the prognosis of the tumor and efficacy of various treatment modalities provides a reliable source for efficient treatment of affected patients. This study presents our 11-year experience with US in the south of Iran. METHODS: Medical records of 42 patients (2001-2012) with endometrial stromal sarcoma (ESS), leiomyosarcoma (LMS), and malignant mixed Müllerian tumor (MMMT) were investigated. Hazard ratio (HR) and 2- and 5-year survival of patients were analyzed based on the patients' age, histopathological characteristics (tumor type, stage, necrosis, and mitotic index), and treatment modalities. RESULTS: Twenty-four patients survived with median follow-up of 42.5 months; 18 died within 17 months, and 52.4% had recurrence, of whom 12 died. Two- and five-year survival rate was 78.6% and 61.9%, respectively, longest for ESS and shortest for MMMT. Higher age, tumor stage, necrosis, and mitotic index increased the HR of mortality. Radiotherapy resulted in a better survival, compared with chemotherapy alone or combined with radiotherapy. CONCLUSION: Although ESS had the best prognosis, MMMT was the most aggressive tumor with the shortest survival time. Histological type of the tumor, staging, tumor necrosis, and mitotic index had prognostic roles. Adjuvant radiotherapy resulted in a better survival, compared with surgery alone in early stage.