Disseminated protothecosis: Case report and review of the literature.

BACKGROUND: Human protothecosis is an uncommon infection caused by Prototheca spp that rarely infects humans. AIM: Description of a rare disease and a review of its articles. MATERIALS AND METHODS: We reported a 24-year-old man who presented with red-brown papules and plaques on the trunk's lateral side. We reviewed the literature about disseminated protothecosis and reported our experience with a patient with protothecosis between 2021 and 2023. RESULTS: Overall, 54 cases of disseminated protothecosis were evaluated, 39 were due to P. wickerhamii, 12 were due to P. zopfii (22.2%), and three were due to Prototheca spp. We found that males were more affected (37 cases, 68.5%) than females (16 cases, 29.6%). The mean age of patients was 39.53 ± 22.48 years. However, disseminated protothecosis can affect people of any age (1-80 years). In contrast to P. wickerhamii, which causes blood, skin, brain, and gastrointestinal tract infections, P. zopfii was mainly found in the blood (7/22) and did not have a significant difference in the mortality rate (P = 0.11). DISCUSSION: Disseminated protothecosis is a rare disease in immunocompromised patients but is generally rarer in immunocompetent hosts. Several underlying disorders include immunocompromised patients, prolonged application of steroids, diabetes mellitus, malignancies, organ transplantation, AIDS, and surgeries. Amphotericin B has been the most effective agent for protothecosis and is reserved for visceral and disseminated infections. Regarding localized cutaneous types, excision or surgical debridement is used. CONCLUSION: Mulberry's appearance and appropriate cultural environments are helpful in diagnosing it.

Punctate Pattern and Pemphigus: Is There Any Evidence of Punctate Pattern Among Iranian Patients?

AIM: To examine the prevalence of this novel pattern among Iranian patients with pemphigus and peruse the relationship between the presence of a punctate pattern with clinical severity of disease and histopathological findings. METHODS: One hundred recently diagnosed patients with pemphigus were enrolled. DIF evaluation and routine light microscopy were performed on their biopsy specimens. Disease severity was determined using the Pemphigus Disease Area Index. Serum samples were collected to measure autoantibody titers using enzyme-linked immunosorbent assay. RESULTS: All the samples evaluated by DIF showed a continuous linear pattern of intercellular IgG deposition, whereas none of them had a punctate pattern. Despite a significant correlation between the Pemphigus Disease Area Index score and autoantibody values, no association between histopathological findings and disease severity has been found. CONCLUSION: We could not detect any punctate pattern among Iranian patients with pemphigus. The importance of this pattern in the diagnosis of pemphigus might be different among patients with different ethnic and genetic factors.

Clinical and histopathological evaluation of cutaneous angiofibromas.

BACKGROUND: Angiofibromas are common benign skin lesions that are diagnosed clinically and histopathologically. Fibrous papule (FP) is one of the clinical types of angiofibromas located primarily on the nose. METHODS: The cases with the confirmed diagnosis of angiofibroma were enrolled. Demographic features of the patients and clinical characteristics of the lesions were extracted. Moreover, histopathological features of the available slides were microscopically reviewed. RESULTS: From 83 cases of cutaneous angiofibromas, 57 (69%) had lesions consistent with FP. The mean age at diagnosis was 37.7 ± 16.3 years and the most common site of involvement was the nose (53% of cases). Regarding the histopathological evaluation of 71 slides, most cases represented vascular changes (97%) and dermal fibroplasia (87%). Melanin incontinence (41%), acanthosis (31%), and lichenoid features (25%) were other common histopathological findings. Moreover, a sparse inflammatory cell infiltrate was present in 68% of cases. The most prevalent inflammatory cells were lymphocytes (61%) and histiocytes (34%). CONCLUSION: This study presented the histopathological findings of a series of cutaneous angiofibromas. Dermatopathologists should be aware of these features, especially those that are less common, to better diagnose and differentiate them from malignant neoplasms.

A comparative study of long interspersed element-1 protein immunoreactivity in cutaneous malignancies.

BACKGROUND: Skin cancer is the most common cancer worldwide and commonly classified into malignant melanoma (MM) and Nonmelanoma skin cancers (NMSCs), which mainly include basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). The extent to which Long Interspersed Element-1 (LINE-1, L1) ORF1p is expressed in cutaneous malignancies remains to be evaluated. This study aimed to assess LINE-1 ORF1p immunoreactivity in various skin cancer subtypes. METHOD: The expression level of LINE-1 ORF1p was evaluated in 95 skin cancer specimens comprising 36 (37.9%) BCC, 28 (29.5%) SCC, and 31 (32.6%) melanoma using the tissue microarray (TMA) technique. Then the association between expression of LINE-1 encoded protein and clinicopathological parameters was analyzed. RESULTS: We showed that LINE-1 ORF1p expression level was substantially higher in BCC and SCC patients compared with melanoma samples (p < 0.001). BCC cases had a higher LINE-1 histochemical score (H-score) compared with SCC cases (p = 0.004). In SCC samples, a lower level of LINE-1 ORF1p expression was associated with age younger than the mean (p = 0.041). At the same time, no significant correlation was found between LINE-1 ORF1p expression and other clinicopathological parameters (all p > 0.05). CONCLUSIONS: According to our observation, LINE-1 ORF1p immunoreactivity in various skin tumor subtypes extends previous studies of LINE-1 expression in different cancers. LINE-1ORF1p overexpression in NMSCs compared with MM can be considered with caution as a tumor-specific antigen for NMSCs.

C4d immunohistochemical stain of formalin-fixed paraffin-embedded tissue as a sensitive method in the diagnosis of bullous pemphigoid.

BACKGROUND: Bullous pemphigoid (BP) is the most common type of subepidermal bullous disease. Direct immunofluorescence (DIF) is the gold standard for diagnosis, but it requires a fresh tissue specimen. This study was conducted to evaluate the accuracy of using immunohistochemical (IHC) analysis for the detection of C4d in paraffin-embedded tissue of BP cases. METHODS: A retrospective study was performed on 30 BP cases (confirmed by Hematoxylin and eosin [H&E] and DIF) and 30 controls. IHC studies were performed on formalin-fixed paraffin-embedded (FFPE) tissues. RESULTS: Of 30 BP patients (11 male and 19 female), 27 (90%) were C4d positive and three patients (10%) were C4d negative. The C4d deposits were seen as linear brown stain along the dermoepidermal junction (18 cases), around basal keratinocytes (eight cases), or Civatte-like (three cases). Two cases revealed more than one pattern in IHC staining. Of 30 control specimens, 26 (86%) cases were C4d negative and four (13.4%) were positive for granular deposits of C4d which were diagnosed as dermatitis herpetiformis. CONCLUSION: C4d IHC study is a valuable diagnostic tool with sensitivity of 90% and specificity of 86.7%, and is especially useful in cases in which frozen specimens are not available or FFPE specimens are the only available material for analysis.

Characteristic features of cutaneous melanoma in a dermatology referral centre in Tehran, Iran.

BACKGROUND/OBJECTIVES: The characteristics of cutaneous melanoma in the Middle-Eastern countries is poorly described. Therefore we conducted this study to determine the characteristics of melanoma in Iran. METHODS: A retrospective, cross sectional study of melanoma patients seen at a tertiary referral centre, Iran, from May 2004 to October 2014. Clinical data included age and gender of the patients at the time of diagnosis, tumour location and tumour size. Histological characteristics included Breslow thickness, Clark level and subtype of tumour. RESULTS: A total of 450 cases of melanoma with a male/female ratio of 1.1:1 were reviewed. The mean age of patients was 57.5 years. The most frequent histological subtypes were acral lentiginous melanoma (30%) and lentigo maligna melanoma (29%). In 215 cases (49%) the tumour was located on the extremities. The second most common site was the face. Tumour invasion was mainly at Clark level III and IV. The mean Breslow thickness was 2.8 mm; 143 (38%) melanomas had a Breslow thickness less than 1 mm (T1) and 86 (23%) were more than 4 mm (T4). CONCLUSION: This study indicates that clinical and histological features of melanoma in Iranians (who are mainly of skin phototypes 3-4) are different from those observed in Western countries. Further cohort studies are required to evaluate the role of ethnic and environmental risk factors for melanoma in different populations.

A case of IgA pemphigus, with a poor response to dapsone, successfully treated with adalimumab.

Key Clinical Message: IgA pemphigus is usually treated by Dapsone. Recalcitrant cases may be treated by Colchicine, Sulfapyridine, or Acitretin. Some patients with recurrent severe disease may not respond to the aforementioned medications. Our study highlights the role of TNFa inhibitor as an alternative modality in the treatment of recalcitrant IgA pemphigus. Abstract: IgA pemphigus is a rare autoimmune blistering disease characterized by a pruritic, annular, vesiculopustular eruption. In IgA pemphigus, there are IgA autoantibodies targeting the keratinocyte cell surface adhesion molecules, causing cell-to-cell dehiscence and a flaccid vesiculopustular eruption, mainly in the axilla and groin. Dapsone, despite being the drug of choice for treating IgA pemphigus, is not effective in clearing lesions in a minority of patients and such rare cases of recalcitrant IgA pemphigus need alternative modalities of treatment. Here, we report the successful treatment of a 50-year-old male patient with an adalimumab injection who had a poor response to dapsone.

Contribution of the latent transforming growth factor-ß binding protein 2 gene to etiology of primary open angle glaucoma and pseudoexfoliation syndrome.

PURPOSE: To assess for the first time the possible contribution of latent transforming growth factor (TGF)-beta binding protein 2 (LTBP2), an extracellular matrix (ECM) protein that associates with fibrillin-1-containing microfibrils, to the etiology of primary open angle glaucoma (POAG) and pseudoexfoliation (PEX) syndrome. Mutations in LTBP2 have previously been shown to be the cause of primary congenital glaucoma (PCG) and other disorders that often manifest as secondary glaucoma. METHODS: All exons of LTBP2 were sequenced in the DNA of 42 unrelated patients with POAG and 48 unrelated patients with PEX syndrome. Contribution of candidate variations to disease was assessed by screening in control individuals and use of biochemical, bioinformatics, and evolutionary criteria, and in one case by segregation analysis within the family of a proband with POAG. Microscopy was performed on the skin of a patient with PEX syndrome whose condition developed into PEX glaucoma during the course of the study and on the skin of her son previously identified with PCG who harbored the same LTBP2 mutation. RESULTS: Among the 30 sequence variations observed in LTBP2, five found in five patients with POAG and two found in two patients with PEX glaucoma syndrome may contribute to their diseases. One of the mutations was observed in a patient with POAG and in a patient with PEX glaucoma syndrome. Light, fluorescent, and electron microscopy showed that a mutation present in one of the individuals affected with PEX glaucoma syndrome and in her son affected with PCG causes disruptions in the ECM. CONCLUSIONS: Some LTBP2 sequence variations can contribute to the etiology of POAG and PEX glaucoma syndrome. It is not expected that in these diseases LTBP2 mutations behave in a strictly Mendelian fashion with complete penetrance. In conjunction with recent findings, the results suggest that anomalies in the ECM are among the factors that can contribute to POAG and PEX glaucoma syndrome. LTBP2 and other related ECM protein coding genes should be screened in larger cohorts with these diseases, which are common disorders and important to the public health.

Pre-operative assessment of basal cell carcinoma dimensions using high frequency ultrasonography and its correlation with histopathology.

INTRODUCTION: High frequency ultrasonography (HFUS) is a non-invasive, low risk method which can provide real-time visual information regarding different processes in cutaneous tissue. The goal of this study is to compare the accuracy of HFUS in determining depth and width of basal cell carcinoma (BCC) lesions compared with histopathology as a reference standard. METHODS: The depth and width of 56 primary BCCs in various locations were measured in vivo using the ultrasound system device Digital Taberna Promedica (Luneburg, FRG DUB 20 Ultrasound Scanner), with a 50-MHz hand-held transducer and compared with the depth and width reported in histopathologic examination of these lesions after complete excision. The intraclass correlation coefficient (ICC) was calculated using a one-way ANOVA table to compare measured dimensions for the same tumors with the two diagnostic methods. RESULTS: The mean depth of tumor in HFUS (1353.68 ± 656.456 microns) was lower than the amount measured by the dermatopathologist (1560.71 ± 1044.323 microns). However, the difference was not statistically significant (P > 0.05). The means of largest diameter of tumors in HFUS and pathology were 5996.77 ± 2271.783 and 3891.07 ± 1995.452 microns, respectively (P < 0.001). There was a low correlation in diameter (r = 0.27, P < 0.05) and a moderate correlation in depth (r = 0.45, P < 0.001) of BCCs between these two methods. CONCLUSION: HFUS may be a useful method to assess the dimensions of BCC prior to surgery.

A keratotic nodule on a cobblestone plaque: A rare case presentation.

The manuscript describes a case of a 68-year-old woman with a pruritic nodule and yellow cobblestone plaque on her abdomen. Biopsy results showed trans epidermal illumination of basophilic elastic fibres in the reticular dermis with calcium deposits. The diagnosis was perforating calcific elastosis, an acquired rare condition mostly seen in obese, multiparous, middle-aged women.

Clinicopathological Study of 307 Patients with Lichen Planus Actinicus and Pigmentosus Referred to Razi Skin Hospital From 2016 to 2021.

INTRODUCTION: The two less-known subtypes of lichen planus (LP) are lichen planus actinicus (LPA) and lichen planus pigmentosus (LPP), with the highest prevalence in the Middle East. OBJECTIVES: We aimed to evaluate the clinicopathological profile of these patients. METHODS: Three hundred and seven cases including 184 LPA and 123 LPP patients were recruited from the registered pathology reports of Razi Skin Hospital of Tehran from April 2016 to March 2021. The clinical features and pathological reports were extracted and analyzed. RESULTS: Among 307 patients, 117 (63.9%) in the LPA group and 88 (71.5%) in the LPP group were women. Duration of disease ranged from 1 month to 20 years and 1 month to 12 years in the LPA and LPP groups, respectively. Face (159 patients), limbs (68), and neck (23) were the most frequent sites of involvement in LPA patients, whereas face (60 patients), limbs (47), and trunk (42) were more commonly involved in the LPP patients. Pruritus and oral mucosal lesions were found with similar frequency in both groups. Pathological evaluation showed vacuolar degeneration of basal layer (100%), lymphocytes infiltration (97.3%), and melanin incontinence (58.2%) as the most frequent findings in LPA and vacuolar degeneration of basal layer (100%), lymphocytes infiltration (100%), and melanin incontinence (52/8%) as the most frequent findings in LPP cases. CONCLUSIONS: LPA and LPP were both more prevalent among women. Face was the most common site of involvement in both LPA and LPP. Vacuolar degeneration, lymphocyte infiltration, melanin incontinence, and hyperkeratosis were more common histological findings in this study.

Detection of herpes simplex viruses in the oral lesions of patients with pemphigus vulgaris: Is it diagnostic or predictive of disease severity?

Background: Some studies emphasise the relationship between the herpes simplex virus (HSV) and pemphigus. Although the possible role of HSV in the pathogenesis of pemphigus and the severity of the disease is obscure, we aimed to evaluate the presence of herpes simplex viruses (HSV 1/2) in the oral lesions of patients with pemphigus vulgaris and also assess its association with disease severity and types of lesions. Methods: A retrospective study was conducted on collected data in the form of collecting paraffin blocks, slides, and relevant pathology reports and referring to patients' medical records. A questionnaire containing details on the degree of skin, scalp, and mucosal involvement (Pemphigus Disease Area Index (PDAI)) was fulfiled. The immunoassay result was also collected to check the anti-desmoglein 3 and 1 antibodies (using ELISA technique). Results: In this study, 52 patients of pemphigus vulgaris with oral lesions (case) and 52 patients with oral lesions not related to the disease (control) were evaluated. HSV1 was detected in 13.5% of oral pemphigus lesions and 1.9% of the control group (p = 0.0598). There were no positive cases of HSV2 in either group. There was no significant association between the positivity of HSV1 and the site of lesions (p = 1.00) or disease severity (p = 0.28). However, we found a strong correlation between the PDAI disease severity score with the titre of the AntiDsg3 antibody (r = 0.487, p = 0.001) and AntiDsg1 antibody (r = 0.309, p = 0.026). Conclusion: This study demonstrated a significant prevalence of HSV1 in oral pemphigus lesions, and acyclovir therapy may play a significant role in managing these patients. However, HSV's role in the pathogenesis of pemphigus vulgaris cannot be clearly determined.

Clinicopathological Survey of 204 Rosacea Patients Regarding Rosacea Subgroups and Severity.

INTRODUCTION: Few studies have evaluated the histopathological characteristics of clinical rosacea subtypes in detail. OBJECTIVES: To assess rosacea histopathological features in correspondence to clinical subgroups. METHODS: The histopathological findings of 204 rosacea patients were analyzed retrospectively and were compared among clinical subtypes. RESULTS: Thirt-Two Percent of patients were male and 68% were female. Seventy-three patients had erythematotelangiectatic rosacea (ETR) and 110 had papulopustular rosacea (PPR), 12 were ETR + PPR, 4 ocular, 2 phymatous, and 3 had Morbihan's edema. Perivascular and perifollicular lymphohistiocytic infiltration, perifollicular exocytosis, follicular spongiosis, and ectatic vessels were almost found in all subtypes. Solar elastosis was higher in ETR. Spongiosis, exocytosis of inflammatory cells into epidermis, acanthosis, and granulomatous reaction were higher in PPR. Inflammatory cells exocytosis was more in PPR and phymatous. Demodex folliculorum was identified in 27% of ETR, 33.6% of PPR, 50% of phymatous, one ocular patient, and none of Morbihan edema. Demodex brevis were found in 5% of ETR, 3% of PPR, and 50% of phymatous. Demodex brevis not folliculorum was more in phymatous. Spongiosis was the most common finding in ocular rosacea. CONCLUSIONS: Spongiosis, exocytosis of inflammatory cells, and granulomatous reactions were more in PPR. Solar elastosis was more in ETR. Histopathological findings were compatible with clinical subgroups.

LTBP2 mutations cause Weill-Marchesani and Weill-Marchesani-like syndrome and affect disruptions in the extracellular matrix.

Latent transforming growth factor (TGF) beta-binding protein 2 (LTBP2) is an extracellular matrix (ECM) protein that associates with fibrillin-1 containing microfibrils. Various factors prompted considering LTBP2 in the etiology of isolated ectopia lentis and associated conditions such as Weill-Marchesani syndrome (WMS) and Marfan syndrome (MFS). LTBP2 was screened in 30 unrelated Iranian patients. Mutations were found only in one WMS proband and one MFS proband. Homozygous c.3529G>A (p.Val1177Met) was shown to cause autosomal recessive WMS or WM-like syndrome by several approaches, including homozygosity mapping. Light, fluorescent, and electron microscopy evidenced disruptions of the microfibrillar network in the ECM of the proband's skin. In conjunction with recent findings regarding other ECM proteins, the results presented strongly support the contention that anomalies in WMS patients are due to disruptions in the ECM. Heterozygous c.1642C >T (p.Arg548*) possibly contributed to MFS-related phenotypes, including ocular manifestations, mitral valve prolapse, and pectus excavatum, but was not cause of MFS.

Cutaneous metastasis of renal cell carcinoma: a case report.

Cutaneous metastasis develops in 5 to 10 percent of high-stage cancer patients. About 6 percent of cutaneous metastases are caused by renal cell carcinomas (RCC). A 64-year-old man presented with a 4-month history of a rapidly enlarging lesion on the mental region. There was a 2 cm x 3 cm multilobular and polypoid angiomatous tumor in the center of the swelling. Histopathologic examination revealed clear cell proliferation with gland formation and red blood cell (RBC) extravasation, compatible with metastatic renal cell carcinoma. The rich vascular structure of RCCs facilitates hematogenous extension and the development of distant metastasis. Arteriovenous and systemic shunts are thought to facilitate the tumor cells' path to the head and neck region. RCC cutaneous metastasis is known to have a vascular appearance. It is important to consider RCC metastasis in the differential diagnosis of new onset tumors with a vascular appearance in the head and neck region.