Pathophysiology, Histopathology, and Differential Diagnostics of Basal Cell Carcinoma and Cutaneous Squamous Cell Carcinoma-An Update from the Pathologist's Point of View.

Basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC) are the most frequently occurring non-melanocytic skin cancers. The objective of our study is to present the pathophysiology of BCC and cSCC and its direct relationship with the histopathological diagnostics and the differential diagnostics of these types of cancer, based on the morphological characteristics, immunohistochemical profile, and genetic alterations. The qualitative study was based on emphasizing the morphological characteristics and immunohistochemistry profiles of BCC and cSCC and the differential diagnostics based on the tissue samples from the Clinical Pathology Department of Mures Clinical County Hospital between 2020 and 2022. We analyzed the histopathological appearances and immunohistochemical profiles of BCC and cSCC in comparison with those of Bowen disease, keratoacanthoma, hyperkeratotic squamous papilloma, metatypical carcinoma, pilomatricoma, trichoblastoma, Merkel cell carcinoma, pleomorphic dermal sarcoma (PDS), and melanoma. Our study showed the importance of the correct histopathological diagnosis, which has a direct impact on the appropriate treatment and outcome for each patient. The study highlighted the histopathological and morphological characteristics of NMSCs and the precursor lesions in HE and the immunohistochemical profile for lesions that may make the differential diagnosis difficult to establish.

Actualities in the Morphology and Immunohistochemistry of Cutaneous and Ocular Melanoma: What Lies Ahead? A Single-Centre Study.

Melanoma is the most aggressive melanocytic tumor whose incidence is continuously increasing worldwide. METHODS: We highlight the morphological, immunohistochemistry, and particularities of various melanoma types based on the cases diagnosed in our department from 2017 to 2021. RESULTS: We present 100 melanoma cases and one capsular nevus case. The most common type was nodular melanoma. The immunohistochemistry markers used were SRY-box transcription factor 10 (SOX10), S100 protein, human melanoma black 45 (HMB45), and melanoma antigen recognized by T cells 1 (Melan-A). Uveal melanoma and conjunctival melanoma represent particular tumors with independent prognostic factors. Uveal melanoma requires assessment of macrophages, microvascularisation, and mitoses. Sentinel lymph node metastases are essential targets that provide staging tools. Conjunctival melanoma and capsular nevi are diagnostic pitfalls. CONCLUSION: Melanoma can appear in various forms, and sometimes the diagnosis might be unclear. Today, immunohistochemistry remains the most important tool in confirming the diagnosis and prognosis for this type of neoplasia.

Melasma treatment: a systematic review.

Melasma is a common chronic refractory disorder of pigmentation affecting people with darker skin types. Overall prevalence varies between 8.8% and 40%, depending on the ethnicity of the population and the geographical area. Therapeutic management of melasma is challenging, with high recurrence rates which significant impacts on the quality of life. No single treatment is universally efficacious. Systemic treatments with tranexamic acid and polypodium leucotmatous had promising results, although the former was related to systemic side effects. Microneedling and peeling were also efficacious, although their superiority to topical hydroquinone, the gold standard in melasma treatment, remains to be established. Similarly, laser and light devices have been beneficial. However, recurrence rates remain high in all treatment groups. Combination therapies, either in double or triple combinations yielded the best results when compared to single terapies. Treatment choice should be made after Wood's lamp examination, as well as dermatoscopic evaluation, in order to select the best treatment option, targeted at each melasma subtype.

The Impact of and Adaptations Due to the COVID-19 Pandemic on the Histopathological Diagnosis of Skin Pathologies, Including Non-Melanocyte and Melanoma Skin Cancers-A Single-Center Study in Romania.

Background and Objectives: The COVID-19 pandemic has globally affected health systems and services. Non-melanoma skin cancers (NMSCs) are the most common malignancies around the world. This study aimed to analyze the differences in the benign and malignant histopathological diagnoses performed on radical excision skin tumors and skin biopsies in the dermatopathology ward in Mures Clinical County Hospital, Targu Mures, Romania, 1 year prior to and during the COVID-19 pandemic, to emphasize the changes in the diagnostic process as per the new regulations. Materials and Methods: A total of 1168 histopathological diagnoses were included in the study-302 from the COVID-19 period and 866 from the non-COVID-19 period-considering the number, type, and frequency of the histopathological diagnoses as variables to be analyzed. Results: In the COVID-19 period, out of the 55 NMSC and melanoma histopathological diagnoses, 50.9% (n = 28) were BCCs, 20% (n = 11) were SCCs, 10.9% (n = 6) were basosquamous cell carcinomas, and 18.18% (n = 10) were melanoma cases. Regarding the non-COVID-19 period, out of the 173 NMSC and melanoma histopathological diagnoses, 46.82% (n = 81) were BCCs, 22.54% (n = 39) were SCCs, 7.51% (n = 13) were basosquamous cell carcinomas, and 23.12% (n = 40) were melanoma cases. Conclusions: During the COVID-19 pandemic, a decrease in histopathological diagnoses at the dermatopathology ward in our hospital was observed, for both benign and malignant pathologies, especially for NMSCs and melanomas, compared to the same period 1 year prior to the pandemic.

CK 8∕18: the key to differentiating intracutaneous lesions with pagetoid features.

INTRODUCTION: Neoplasms with pagetoid features are a category of rare lesions defined by the presence of atypical cells at different levels of the epidermis. The most important diseases within this category are mammary Paget disease (MPD), extramammary Paget disease (EMPD), Bowen's disease, in situ melanoma, and pagetoid reticulosis. AIM: The aim of this analysis was to describe the importance of the cytokeratin 8∕18 (CK 8∕18) immunostaining in diagnosing MPD and EMPD and differentiating them from other lesions. MATERIALS AND METHODS: A retrospective study was employed, based on the histopathological and immunohistochemical (IHC) characteristics of 30 cases that presented pagetoid features. The cases were processed and analyzed at the Department of Pathology, Mures Clinical County Hospital, Târgu Mures, Romania, from 2017 to 2020. RESULTS: Five MPD cases, one EMPD case, one pagetoid reticulosis case, 10 Bowen's disease cases, and 13 in situ melanoma cases were collected. Under Hematoxylin-Eosin staining, cells presented pale cytoplasm in MPD, EMPD, and in 25% of the melanoma cases. Hyperchromasia with nuclear enlargement was seen in all cases. Immunostaining with CK 8∕18 was positive in all MPD and EMPD cases. Tests for CK7, p63, and CK AE1∕AE3 were positive in MPD, EMPD, and Bowen's cases. Tests for S100, SRY-box transcription factor 10 (SOX10), human melanoma black 45 (HMB45), and Melan A were positive in melanoma cases, while cluster of differentiation (CD)3, CD4, and CD8 tests were positive in the pagetoid reticulosis case. CONCLUSIONS: CK 8∕18 is an IHC marker that can help establish the diagnosis of MPD and EMPD and differentiate them from other pagetoid neoplasms, ensuring the proper diagnosis and prognosis are provided.

Neuroendocrine tumors (NETs) - experience of a single Center.

INTRODUCTION: Neuroendocrine neoplasms (NENs) are a heterogeneous group of tumors arising from cells that are part of the diffuse neuroendocrine system. PATIENTS, MATERIALS AND METHODS: We conducted a retrospective study in which we included a number of 91 cases diagnosed with neuroendocrine tumors (NETs). Descriptive statistics was performed: number of cases based on location, distribution by gender (male∕female), distribution by age, and we also performed a morphological and immunohistochemical (IHC) study. RESULTS: The highest number of cases was found in lungs (60 cases). Tumors located on the skin, breast or bladder have been discovered, locations considered rare for this type of tumor. Of all cases diagnosed in the lungs, 59 were diagnosed as small cell carcinomas (SCCs) and only one case as NET. All surgical specimens were positive for chromogranin A (CgA), with a different expression for the other immunomarkers. For the lung biopsies, the most frequently IHC staining was CgA and cluster of differentiation 56 (CD56), with an increased positivity for the latter. CONCLUSIONS: CgA remains the most sensitive immunomarker in the diagnosis of NETs. CD56 is the most widely used immunomarker for diagnosing small cell lung tumors. Positive expression of thyroid transcription factor 1 (TTF1) immunomarker does not confirm pulmonary origin of SCCs.

Human Papillomavirus (HPV) Infection and HPV Vaccination: Assessing the Level of Knowledge among Students of the University of Medicine and Pharmacy of Tîrgu Mures, Romania.

Human papillomavirus (HPV) infection, a causative factor for cervical cancer, remains a topic of great interest. About 80% of sexually active women are at risk of acquiring an HPV infection at some point in life, the peak incidence of infection having been identified in young women. The aim of the study was to assess the knowledge and attitudes of medical students about sexually transmitted diseases, HPV infection, HPV vaccinations, and student sexual behavior. A transversal study was conducted using a questionnaire on students on the 1st and 6th year at the Faculty of Medicine of Tîrgu Mures University, Romania. The study resulted in 522 fully completed questionnaires. The percentage of students who had heard about HPV was 82.1% in the 1st year and 99.1% in the 6th year of medical school, but the level of knowledge was different: 62% of senior students had a good or very good level of knowledge, whereas 55.1% of first year students had little knowledge on the topic. About 75% of 6th year students would vaccinate their child against HPV, compared with only 52.4% of 1st year students (P<0.001). The level of knowledge about HPV infection among students in their first year of medical school is rather low, significantly lower compared to 6th year students, which suggests acquiring some basic information in this area since the first year of college or even high school.

The value of histopathological diagnosis in the elderly patients with granulomatous dermatoses. Case series.

Granulomatous inflammations are a particular type of chronic septic or aseptic inflammation, in which infectious or non-infectious agents are difficult to eliminate by the immune system. These are type IV hypersensitivity reactions mediated by pre-sensitized T-lymphocytes cells CD4+ and CD8+ lymphocytes. Disorders included in this category are: tuberculosis, leprosy, syphilis, sarcoidosis, type I diabetes, multiple sclerosis, Crohn's disease and rheumatoid arthritis. At cutaneous level, this pattern of granulomatous reaction is characterized by a chronic inflammation with formation of granulomas consisting of a variable number of histiocytes, multinucleated giant cells and lymphocytes. Granulomatous dermatoses should be differentiated from other primary or secondary lesions affecting the skin such as inflammation or tumors. Often granulomatous dermatoses can be confused with other skin disorders, both clinically and histological. Histopathology examination can add important information and clarify the diagnosis. This paper presents a series of three clinical cases of granulomatous skin occurring in the elderly patients confirmed at histology examination. Clinical and histology criteria were analyzed, along with specific differential diagnosis, based on data from the literature.

Multiple asymptomatic cutaneous pilar leiomyoma versus spontaneous eruptive keloids - a case report.

Cutaneous piloleiomyoma, angioleiomyoma and genital leiomyoma are variants of superficial cutaneous leiomyoma. The main purpose of this paper was to present clinical, histopathological and immunohistochemical diagnosis criteria for an unusual case of pilar leiomyoma in an 18-year-old male patient. The initial clinical aspect was very similar to spontaneous eruptive keloids: red-violet color, painless, aspect of "crab pincers" of some of the lesions, epidermis atrophy, telangiectasia, located on acneiform zones and compliance with cephalic extremity. The patient had no history of trauma, surgery or acne. Local treatment of one lesion was performed with cryotherapy using liquid nitrogen (-172°C) together with intra-lesion steroid injections, occlusive dressings and silicone gel. Local therapy did not showed notable results, moreover the lesion become painful. Skin biopsy with histological and immunohistochemical analysis revealed the diagnosis of multiple cutaneous pilar leiomyoma without atypia. The particularity of the case stands in the atypical onset followed by explosive increasing of lesions number and the appearance of pathognomonic pain after local therapy.

Human Papillomavirus Vaccine - Knowledge and Attitudes among Parents of Children Aged 10-14 Years: a Cross-sectional Study, Tîrgu Mures, Romania.

AIM: Romania ranks first in Europe in terms of mortality from cervical cancer, recording 6.3 times more deaths than the mean in EU countries. Although vaccination campaigns were launched by health officials in Romania, the acceptance rate remained insignificant and programmes were discontinued. A successful vaccination programme requires a high rate of acceptance and accurate information for health professionals and parents. The aim of the study was to evaluate the level of parental knowledge about human papilomavirus (HPV) infection and HPV vaccination including the information obtained from general practitioners and identification of barriers in implementing a vaccination strategy. METHODS: We performed a cross-sectional study using a self-administered questionnaire for the parents of pupils in grades 5-8, in three randomly selected secondary schools in Tîrgu Mures, Romania. RESULTS: We surveyed 918 parents. Of the respondents, 85.8% have heard of HPV infection. Most reported an average level of knowledge about HPV infection and HPV vaccination. The two main sources of information were specialized healthcare professionals (42.8% for HPV infection, 39.1% for HPV vaccination) and the Internet browsing (42.3% and 42.9%, respectively). Based on current knowledge, only one third of parents would have their child vaccinated against HPV infection. According to most parents surveyed, the main reasons for not wanting to have their child vaccinated is the fear of side effects; the vaccine is new and insufficiently studied; or parents do not know details about the vaccine. CONCLUSIONS: The parents showed the average level of knowledge about HPV infection and HPV vaccination. The implementation of an effective programme to increase the acceptance rate of HPV vaccination requires educational strategies aimed at involving parents and their children and supported by general practitioners and public health professionals.

Necrotizing fasciitis in oro-maxillo-facial area after radiotherapy for squamous cell carcinoma of the soft palate.

The fascia's and subcutaneous adipose tissue's impairment by mono or polymicrobial infection, which also can involve the skin and the muscles, is rarely seen in oro-maxillo-facial area. The present case report is presenting a case of necrotizing fasciitis in a patient who had a history of an invasive squamous cell carcinoma of the soft palate, with surgical treatment and with radiotherapy. He was admitted in our Clinic with malaise and subsequently developed a toxico-septic shock. Clinical symptoms, serological and bacteriological analysis and histopathological examination confirmed the diagnosis of necrotizing fasciitis (NF). The patient subsequently underwent a series of surgical reconstruction and aesthetic treatments because of the complications that had arised in the meantime. Postoperative evolution was favorable towards complete closure of the defect. The prognosis of this disease is generally reserved, the favorable evolution depending on the possibility of wound sterilization and the surgery is required despite its mutilating effect.

Aneurysmal dermatofibroma mimicking both clinical and dermoscopic malignant melanoma and Kaposi's sarcoma.

Aneurysmal dermatofibroma (AD) or aneurysmal fibrous histiocytoma (AFH) is a relatively rare form of histiocytoma representing less than 2% of total cases. It shares many clinical and dermoscopic similarities with skin tumors, especially malignant melanoma and Kaposi's sarcoma, which can make differentiation problematic. We report the case of a 53-year-old man, who presents with a black nodular tumor with increased consistency, edges infiltrated from the surface to depth, spontaneous and sensitive to touch that shows rapid growth in the last three months. Dermoscopically, the central region consists of intricate areas colored in red, violet, blue-white and black. On the periphery stand two rings, centrally white and peripherally pigmented, with an abundance of polymorphic capillaries. To clarify the diagnosis, the lesion was widely excised and histopathological examination was performed, which revealed immunophenotypical tumor cells negative for HMB-45 and S100, and numerous CD68 macrophages between tumor cells. This aneurysmal fibrous histiocytoma shows both clinical and dermoscopically discrete differential criteria, which are not specific and that make it difficult to distinguish from malignant melanoma and Kaposi's sarcoma, and required performing histopathology and immunohistochemistry.

Oral squamous cell carcinoma of the maxilla, a second malignancy after a right ethmoido-maxillary chondrosarcoma.

Squamous cell carcinoma is defined as an invasive epithelial neoplasm, with variable degrees of squamous differentiation, with or without keratinization. It is origins stand at the level of the keratinized stratified squamous epithelium (skin) or non-keratinized (oral mucosa, esophageal mucosa, uterine exocervical mucosa), but it can also be found in squamous metaplasia areas (uterine endocervix or trachea-bronchial tree). This report presents the case of an oral squamous cell carcinoma as a second malignancy in the same anatomical territory, in a patient with prior treatment for chondrosarcoma, both surgical and radiotherapy. The tumor had appeared 5-6 months prior and had undergone a relatively rapid growth, this being the patient's main motive for addressing the doctors. The tumor was greyish, with imprecisely demarcated margins, of firm consistency, bleeding and with local necrotic deposits. The tumor extended from the incisive region to the maxillary tuberosity, towards the cheek mucosa and the soft palate. After a large excision, the histopathological diagnosis was infiltrative keratinizing squamous cell carcinoma, with moderate differentiation, with origins in the oral mucosa, infiltrating the whole of the maxilla and the maxillary sinus mucosa. Approximately three months after the surgery, a new tumor appeared in the oral cavity, on superior and inferior mucosa of the right cheek, extending towards the right buccal commissure, implying a relapse of the primary tumor. Postoperative oncological therapy included standard chemotherapy, which resulted in favorable postoperative evolution. This case is interesting by the association, of two metachronous malignant tumors, of different histological origin: a chondrosarcoma and a squamous cell carcinoma, at an interval of 25 years.

Pagetoid reticulosis Woringer-Kolopp type, a particular variant of mycosis fungoides: a case report.

According to the definition of WHO, pagetoid reticulosis (PR) is characterized by the presence of unique skin lesion in the shape of patches or plaques caused by the proliferation of atypical T-cells in epidermis. We report the case of a 50-year-old female, presenting a 50×65 mm erythematous scaly patch, well-defined, slightly infiltrated, discrete polycyclic, on the right buttock, which appeared and developed in about 6-8 months. The clinical and dermatoscopic aspects suggested a Bowen's disease. A skin biopsy was performed. The histological examination of the pieces confirmed the presence of monoclonal lymphoid infiltrate with obvious phenomena of epidermotropism. Immuno-phenotypically the tumoral cells express intensively CD3 and CD8 and focally CD4. Surgical excision was performed without radiotherapy and chemotherapy. The patient was followed-up for 42 months without local relapses, distant lymph nodes or visceral metastases. Microscopic aspect of the lesion corresponds to stage I-II of mycosis fungoides (MF) (patches or plaques); the diagnosis was PR Woringer-Kolopp type. The most recent classification of skin lymphomas (WHO, 2008) confirms that the immunohistochemical profile of T-cells can be CD4+ and CD8- or CD4- and CD8+, and frequently CD30+, in contrast to the classical versions of MF. Pagetoid reticulosis type Woringer-Kolopp, a rare particular variant of mycosis fungoides, is suspected in cases with unique, distinctive lesion and confirmed only by histological immunohistochemistry. Treatment consists of surgical excision of the lesion with long follow-up.

Giant dermatofibrosarcoma protuberans - rare form of mesenchymal tissue neoplasm: case presentation.

UNLABELLED: Dermatofibrosarcoma protuberans (DFSP), a rare type of mesenchymal neoplasm, is defined by the WHO as a superficial sarcoma with low-grade malignancy that develops in the cutaneous and subcutaneous tissues. The purpose of this paper is to present a case of a giant DFSP, with post-traumatic onset in childhood and a very long evolution. CLINICAL DATA: 51-year-old Caucasian patient presents for 41 years a presternal neoplastic lesion, with onset at 10-year-old, few months after a strong trauma. The patient addressed for a clinic examination, secondary to a spontaneous hemorrhage of the lesion. The local examination reveals the presence of a red-purple polynodular neoplastic lesion of 180×110×30 mm, of firm consistency, adherent to the subcutaneous tissue, painless, with lateral extension at 8 o'clock as an erythematous infiltrated atrophic plaque appearance. One of these nodular masses presents surface ulceration and areas of necrosis. The CT scan did not detect any infiltration into the pectoral muscle or loco-regional metastasis. Under general anesthesia a wide surgical excision with free macroscopic margins of 3 cm was performed. Histopathological diagnosis was DFSP, with evidence of tumoral spindle cells disposed in storiform pattern, embedding small adipocyte panicles, creating a lace-like or honeycomb appearance. Immunohistochemically, the tumor cells express an intense and diffuse CD34 and they are negative for S-100 and SMA. The Ki-67 is focal positive in almost 2-4%. Clinical and paraclinical monitoring at 18 months follow-up does not detect any local recurrences or metastases, and an excellent quality of life.