The Tumor Stroma of Squamous Cell Carcinoma: A Complex Environment That Fuels Cancer Progression.

The tumor microenvironment (TME), a complex assembly of cellular and extracellular matrix (ECM) components, plays a crucial role in driving tumor progression, shaping treatment responses, and influencing metastasis. This narrative review focuses on the cutaneous squamous cell carcinoma (cSCC) tumor stroma, highlighting its key constituents and their dynamic contributions. We examine how significant changes within the cSCC ECM-specifically, alterations in fibronectin, hyaluronic acid, laminins, proteoglycans, and collagens-promote cancer progression, metastasis, and drug resistance. The cellular composition of the cSCC TME is also explored, detailing the intricate interplay of cancer-associated fibroblasts (CAFs), mesenchymal stem cells (MSCs), endothelial cells, pericytes, adipocytes, and various immune cell populations. These diverse players modulate tumor development, angiogenesis, and immune responses. Finally, we emphasize the TME's potential as a therapeutic target. Emerging strategies discussed in this review include harnessing the immune system (adoptive cell transfer, checkpoint blockade), hindering tumor angiogenesis, disrupting CAF activity, and manipulating ECM components. These approaches underscore the vital role that deciphering TME interactions plays in advancing cSCC therapy. Further research illuminating these complex relationships will uncover new avenues for developing more effective treatments for cSCC.

First Reported Case of a Clinically Nonresponsive-to-Itraconazole Alternaria alternata Isolated from a Skin Infection of a Nonimmunocompromised Patient from Romania.

BACKGROUND: Alternaria alternata is a melanic fungus capable of causing a wide variety of infections, some of which have lethal potential. It is a ubiquitous fungus and a well-known plant pathogen. Cutaneous infections with Alternaria alternata most often occur in the extremities of patients who perform conventional agriculture, thus being exposed to occupational hazards leading to the disruption of the skin barrier. METHODS: This paper presents the first case report from Romania of an itraconazole nonresponsive cutaneous alternariosis in a patient without any type of immunosuppression. RESULTS: After an initial misdiagnosis regarding the etiology of the patient's skin infection, two successive punch biopsies, followed by mycologic examination, lead to the final diagnosis of cutaneous alternariosis. Treatment guided by antifungal susceptibility testing has been instituted, leading to the gradual healing of the patient's skin ulcerations. CONCLUSIONS: The ability of Alternaria alternata to infect immunocompetent human hosts and to develop resistance to antifungal drugs highlight the importance of correctly diagnosing the etiology of skin ulcerations and instituting appropriate treatment guided by antifungal susceptibility testing whenever the suspicion of a fungal skin infection is plausible.

The "starry night" (diffuse microcalcific myopathy) - thousands of muscle microcalcifications after 30 years of Trichinella infection detected by ultrasound.

Trichinellosis, a parasitosis transmitted through consumption of raw or undercooked meat from pigs and game animals, is responsible for a specific myositis. The calcifications of infected myocytes and larva can be detected during many years postin-fection. We present the case of a male patient with a history of severe trichinellosis with disease onset 30 years ago, presenting with generalized muscle microcalcifications detected during musculoskeletal ultrasound evaluation. The ultrasound aspect of the muscles was indeed spectacular; hence, the comparison with a "starry night".

Digital histological morphometry of the human pineal gland in a postmortem study, with endocrine and neurological clinical implications.

The pineal gland is a small-sized, photo neuroendocrine organ in the midline of the brain that synthesises and secretes melatonin and serotonin. Chords and islands of pinealocytes constitute the secretory parenchyma, while glial tissue and calcifications represent degenerative changes. This study examined human postmortem pineal glands to microscopically assess morphological changes possibly associated with clinical data, by using digital techniques. A retrospective autopsy study has been performed on 72 paediatric and adult autopsy cases. The glands have been processed for histological analysis and immunohistochemical staining with synaptophysin (SYN), neuron-specific enolase (NSE), and neurofilament (NF). Slides were digitally scanned. Morphometric data were obtained using CaseViewer and ImageJ. The comorbidities used for correlation with morphometric data were obesity, type 2 diabetes, adrenal gland adenoma, goitre, chronic pancreatitis, arterial hypertension, and mixed dementia. Thirty-three females and 39 males were included in the study. Increased secretory parenchyma was found in patients with chronic pancreatitis, arterial hypertension, and adrenal gland adenoma. Reduced activity was found in patients with type 2 diabetes, obesity, advanced pineal calcification, mixed dementia, and old age. There were no changes associated with goitre, cachexia, or Willis's polygon atherosclerosis. No significant differences between gender were found. The activity of the pineal gland can be assessed by quantitative immunohistochemistry of neuroendocrine and structural pinealocyte markers and observation of glial tissue and calcifications. There is a need for further research to evaluate the clinical impact of these morphological changes on the neuroendocrine systems, with clinical implications in endocrinology, neurology, and even psychiatry. Digital techniques offer a more exact analysis of histological data.

Nodular and Micronodular Basal Cell Carcinoma Subtypes Are Different Tumors Based on Their Morphological Architecture and Their Interaction with the Surrounding Stroma.

Basal cell carcinoma (BCC) is the most frequent cancer of the skin and comprises low-risk and high-risk subtypes. We selected a low-risk subtype, namely, nodular (N), and a high-risk subtype, namely, micronodular (MN), with the aim to identify differences between them using a classical morphometric approach through a gray-level co-occurrence matrix and histogram analysis, as well as an approach based on deep learning semantic segmentation. From whole-slide images, pathologists selected 216 N and 201 MN BCC images. The two groups were then manually segmented and compared based on four morphological areas: center of the BCC islands (tumor, T), peripheral palisading of the BCC islands (touching tumor, TT), peritumoral cleft (PC) and surrounding stroma (S). We found that the TT pattern varied the least, while the PC pattern varied the most between the two subtypes. The combination of two distinct analysis approaches yielded fresh insights into the characterization of BCC, and thus, we were able to describe two different morphological patterns for the T component of the two subtypes.

Xanthogranuloma of the Sellar Region: A Comprehensive Review of Neuroimaging in a Rare Inflammatory Entity.

Xanthogranuloma of the sellar region is a rare chronic inflammatory lesion resulting from secondary hemorrhage, inflammation, infarction, and necrosis of an existing Rathke's cleft cyst, craniopharyngioma, or pituitary adenoma. Sellar xanthogranulomas are challenging to differentiate from other cystic lesions preoperatively due to the lack of characteristic imaging features. We performed a literature overview of the clinical and paraclinical features, treatment options, and long-term outcomes of patients with sellar xanthogranuloma, focusing on the preoperative radiological diagnosis. The hyperintense signal in both T1- and T2-weighted sequences, cystic or partially cystic morphology, ovoid shape, sellar epicenter, intra- and suprasellar location, intratumoral calcifications, linear rim contrast enhancement, and the absence of cavernous sinus invasion suggest xanthogranuloma in the preoperative differential diagnosis. An endoscopic endonasal gross total resection without radiotherapy is the preferred first-line treatment. Given the low rate of recurrence rate and low chance of endocrinological recovery, a mass reduction with decompression of the optic apparatus may represent an appropriate surgical goal. Identifying the xanthogranulomas' mutational profile could complement histopathological diagnosis and give insight into their histo-pathogenesis. A better preoperative neuroimagistic diagnosis of sellar xanthogranulomas and differentiation from lesions with a poorer prognosis, such as craniopharyngioma, would result in an optimal personalized surgical approach.

Techniques for digital histological morphometry of the pineal gland.

INTRODUCTION: The pineal gland is a small photo-neuro-endocrine organ. This study used human post-mortem pineal glands to microscopically assess immunohistochemical marker intensity and percentage of positivity using known and novel digital techniques. MATERIALS AND METHODS: An experimental non-inferiority study has been performed on 72 pineal glands harvested from post-mortem examinations. The glands have been stained with glial fibrillary acidic protein (GFAP), synaptophysin (SYN), neuron-specific enolase (NSE), and neurofilament (NF). Slides were digitally scanned. Morphometric data were obtained using optical analysis, CaseViewer, ImageJ, and MorphoRGB RESULTS: Strong and statistically significant correlations were found and plotted using Bland-Altman diagrams between the two image analysis software in the case of mean percentage and intensity of GFAP, NSE, NF, and SYN. DISCUSSIONS: Software such as SlideViewer and ImageJ, with our novel software MorphoRGB were used to perform histological morphometry of the pineal gland. Digital morphometry of a small organ such as the pineal gland is easy to do by using whole slide imaging (WSI) and digital image analysis software, with potential use in clinical settings. MorphoRGB provides slightly more accurate data than ImageJ and is more user-friendly regarding measurements of parenchyma percentage stained by immunohistochemistry. The results show that MorphoRGB is not inferior in functionality. CONCLUSIONS: The described morphometric techniques have potential value in current practice, experimental small animal models and human pineal glands, or other small endocrine organs that can be fully included in a whole slide image. The software we used has applications in quantifying immunohistochemical stains.

Bilateral Hand Metastases From a Pleomorphic/Dedifferentiated Leiomyosarcoma: A Case Report.

ABSTRACT: Leiomyosarcomas of the lower extremity are heterogeneous tumors with high recurrence and metastasizing rates, which, rarely, can suffer a dedifferentiation process, making them extremely aggressive and unpredictable. We report the case of a 72-year-old female patient who presented the clinical and histopathological features of a rare leiomyosarcoma of the foot that was completely excised, but because of the interruption of adjuvant oncological treatment and lack of compliance for the follow-up, the patient suffered a dedifferentiation process and the tumor metastasized in the fingers-an unprecedented site for this type. The present case proves the fact that there is still a lot we do not know about the behavior of this disease, and there is always room to learn. Also, through this report, we are emphasizing a frequently encountered and never-ending problem in our country-that of difficult and resource-consuming cases derived from disconsidering medical advice by noncompliant patients when faced with a malignant diagnosis, making all attempts to offer them a better quality of life futile.

Molecular Pathology and Targeted Therapies for Personalized Management of Central Nervous System Germinoma.

Intracranial germinomas are rare tumours, usually affecting male paediatric patients. They frequently develop in the pineal and suprasellar regions, causing endocrinological disturbances, visual deficits, and increased intracranial pressure. The diagnosis is established on magnetic resonance imaging (MRI), serum and cerebrospinal fluid (CSF) markers, and tumour stereotactic biopsy. Imaging techniques, such as susceptibility-weighted imaging (SWI), T2* (T2-star) gradient echo (GRE) or arterial spin labelling based perfusion-weighted MRI (ASL-PWI) facilitate the diagnosis. Germinomas are highly radiosensitive tumours, with survival rates >90% in the context of chemoradiotherapy. However, patients with resistant disease have limited therapeutic options and poor survival. The aim of this review is to highlight the genetic, epigenetic, and immunologic features, which could provide the basis for targeted therapy. Intracranial germinomas present genetic and epigenetic alterations (chromosomal aberrations, KIT, MAPK and PI3K pathways mutations, DNA hypomethylation, miRNA dysregulation) that may represent targets for therapy. Tyrosine kinase and mTOR inhibitors warrant further investigation in these cases. Immune markers, PD-1 (programmed cell death protein 1) and PD-L1 (programmed death-ligand 1), are expressed in germinomas, representing potential targets for immune checkpoint inhibitors. Resistant cases should benefit from a personalized management: genetic and immunological testing and enrolment in trials evaluating targeted therapies in intracranial germinomas.

MRI findings in-between leiomyoma and leiomyosarcoma: a Rad-Path correlation of degenerated leiomyomas and variants.

Leiomyomas are the most common benign tumors of the uterus. On the opposite side, leiomyosarcomas are rare malignant uterine tumors that account for a significant proportion of uterine cancer deaths. Especially when large and degenerated, leiomyomas and leiomyoma variants can have overlapping imaging characteristics with those of leiomyosarcomas. Although not always possible, it is paramount to be able to differentiate between leiomyomas and leiomyosarcomas on imaging, as the therapeutic management can differ. This pictorial review aims to familiarize radiologists with imaging features of leiomyomas and various types of leiomyoma degeneration and variants, together with their pathology correlates.

Age-Related Changes of the Pineal Gland in Humans: A Digital Anatomo-Histological Morphometric Study on Autopsy Cases with Comparison to Predigital-Era Studies.

Background and objectives: The pineal gland is a photoneuroendocrine organ in the midline of the brain, responsible primarily for melatonin synthesis. It is composed mainly of pinealocytes and glial tissue. This study examined human postmortem pineal glands to microscopically assess age-related changes using digital techniques, and offers a perspective on evolutionary tendencies compared to the past. Materials and Methods: A retrospective autopsy study has been performed on 72 pediatric and adult autopsy cases. The glands have been processed for histological analysis and immunohistochemical staining with glial fibrillary acidic protein (GFAP). Slides were assessed under polarized light and digitally scanned. Morphometric data were obtained using CaseViewer and ImageJ. Results: Thirty-three females and 39 males were included in the study, grouped under three age groups: 0-25, 46-65, and 66-96 years of age. The peak gland volume was found within the 46-65 age group, the overall mean volume was 519 mm3, the main architectural types were lobular and insular, and the mean percentage of pineal calcification was 15% of the gland, peaking within the 66-96 age group, with a predominantly globular shape. Glial cysts were found in 20.8% of cases. The intensity of GFAP stain was maximal in the pediatric age group, but the extent of glial tissue was much larger in elderly patients. Discussion: The degenerative process of the pineal gland can be quantified by measuring normal parenchyma, calcifications, glial tissue, and glial cysts. Morphometric differences have been observed and compared to a similar studies performed in the published literature. The current study, unfortunately, lacks a 26-45 age group. Digital techniques seemed to offer a more exact analysis, but returned similar results to studies performed over 40 years ago, therefore offering important information on evolutionary tendencies. Conclusions: Increase in glial tissue, calcifications, and glial cysts have a defining role as age-related changes in the pineal gland.

Bone Morphogenetic Protein 7 Expression in Alveolar Bone Addition With Autologous Blood, Lyophilized Bone and Atelocollagen.

BACKGROUND/AIM: The biomaterials used in guided bone regeneration have undergone significant diversification in recent years. This study aimed to evaluate alveolar bone addition and bone morphogenetic protein 7 (BMP7) expression using an improved autologous and xenogeneic biomaterial. MATERIALS AND METHODS: Chronic marginal periodontitis was induced in sheep; the intervention group received bone addition as periodontal therapy, using a composite system with lyophilized bovine bone enriched with atelocollagen type 1, platelet-rich plasma and advanced platelet-rich fibrin (A-PRF). Six weeks after the intervention, the dentoalveolar structures were evaluated using hematoxylin-eosin and immunohistochemical staining, to evaluate bone addition and BMP7 expression. RESULTS: The untreated sheep showed inflammation, periodontal ligament destruction, remnants of calculus and bacterial plaque as well as foreign bodies in the desmodontal space, without sings of repair. In the treated sheep, fibroblasts/fibrosis, cartilage and/or new bone, cellular cementum and desmodontium, along with remnants of biomaterial with various degrees of cellularity were observed. In the untreated group, the presence of BMP7 was found in osteoblasts and osteocytes while in the treated group, it was mainly found in the biomaterial remnants, while immunohistochemical staining was less intense in the newly formed osteo-periodontal tissues. Quantitative analysis using the Mann-Whitney U-test showed highly statistically significant differences between the two groups, demonstrating the efficiency of this composite system. CONCLUSION: The current composite system meets all the necessary conditions for promising guided alveolar bone regeneration.

Antitussive, Antioxidant, and Anti-Inflammatory Effects of a Walnut (Juglans regia L.) Septum Extract Rich in Bioactive Compounds.

The antitussive, antioxidant, and anti-inflammatory effects of a walnut (Juglans regia L.) septum extract (WSE), rich in bioactive compounds were investigated using the citric acid aerosol-induced cough experimental model in rodents. Wistar male rats were treated orally for three days with distilled water (control), codeine (reference), and WSE in graded doses. On the third day, all rats were exposed to citric acid aerosols, the number of coughs being recorded. Each animal was sacrificed after exposure, and blood and lung tissue samples were collected for histopathological analysis and the assessment of oxidative stress and inflammatory biomarkers. The results of the experiment showed a significant antitussive effect of WSE, superior to codeine. This activity could be due to cellular protective effect and anti-inflammatory effect via the stimulation of the antioxidant enzyme system and the decrease of IL-6 and CXC-R1 concentration in the lung tissue of WSE-treated animals. The antioxidant and anti-inflammatory effects of WSE were confirmed by biochemical assays and histopathological analysis. This is the first scientific study reporting the antitussive effect of walnut septum, a new potential source of non-opioid antitussive drug candidates, and a valuable bioactive by-product that could be used in the treatment of respiratory diseases.

Antioxidant Effects of Walnut (Juglans regia L.) Kernel and Walnut Septum Extract in a D-Galactose-Induced Aging Model and in Naturally Aged Rats.

Antioxidant dietary intervention is considered a potential strategy in delaying age-related dysfunctions. In this study of 56 days, we assessed the antioxidant effects of walnut kernel (WK) and walnut septum extract (WSE) in a D-galactose (D-gal)-induced aging model and in a naturally aged rat model. Young Wistar rats, treated with D-gal (1200 mg/week), and old rats received daily WK or WSE added to the feed. After 8 weeks, blood, liver, and brain samples were collected and hematological, biochemical, oxidative stress biomarkers, histological, and immunohistochemical analyses were performed. Moreover, acetylcholinesterase activity was investigated in brain homogenates. The outcomes demonstrated significant improvement in cellular antioxidant activity and/or decrease of reactive oxygen species, advanced glycation end products, nitric oxide, malondialdehyde, or increase of glutathione after WK or WSE intake in both models. Additionally, WSE showed hypoglycemic effect, and both WK and WSE lowered acetylcholinesterase activity. Both diets could protect neurons against the induced senescence and could reverse the pathological conditions in the physiological aged brain. Thus, dietary supplementation with WK or WSE can maintain the liver and brain health and reduce the risk of age-related diseases, as well as delaying the onset of aging processes.

Different patterns of p16INK4a immunohistochemical expression and their biological implications in laryngeal squamous cell carcinoma.

INTRODUCTION: p16INK4a immunohistochemistry (IHC) is widely used to facilitate the diagnosis of human papillomavirus (HPV)-associated neoplasia, when ≥70% of cells show strong nuclear and cytoplasmic positivity. In this study, we aim to compare partial expression patterns that do not fulfill the above criteria and seek biological implications in laryngeal squamous cell carcinoma (LSCC). MATERIALS AND METHODS: p16INK4a IHC staining was conducted on representative sections of archived tissue from 88 LSCCs. Immunoreactivity was described based on four parameters: intracellular localization of immunostaining, intensity of immunostaining, distribution pattern and percentage of positive cells. RESULTS: Six patterns of p16INK4a immunoexpression were observed and defined as: strong diffuse (strong immunostaining, expression in cytoplasm and nucleus in >70% of tumor cells), weak diffuse (moderate or weak immunostaining, expression in cytoplasm in >70% of tumor cells), marginal (strong cytoplasmic immunostaining, limited to the periphery of tumor islets), strong scattered (strong immunostaining, expression in cytoplasm and nucleus in <50% of tumor cells), weak scattered (moderate or weak immunostaining, expression in cytoplasm in <50% of tumor cells), negative (no expression). The pN stage of the patients was associated with p16INK4a immunoexpression patterns, the marginal pattern was only found in the pN0-Nx stages, while the weak diffuse pattern was more frequently observed in pN2-N3 stages. CONCLUSIONS: Partial immunostaining with architecturally distinct p16INK4a immunoexpression patterns may prove significant in stratifying characteristic clinicopathological subgroups among LSCC. Our observations may support the hypothesis that p16INK4a has different roles in different subcellular locations, with tumorigenic molecular pathways unrelated to HPV infection.

Unusual Manifestations of Secondary Syphilis: Case Presentations.

Dear Editor, Syphilis is an infection caused by Treponema pallidum. Without treatment, it goes through the following stages: primary, secondary, latent, and tertiary (1). The clinical picture of secondary syphilis is very variable (2,3). We present two rare cases of secondary syphilis, one with nodular lesions initially considered to be lymphoma and second with periostitis, which was initially interpreted as an osteoma. To date, only 15 cases with nodular lesions and 10 cases with periostitis in secondary syphilis have been reported in the literature. The first patient was a 59 year old man who presented in a private practice with nodular lesions on the face and axillary and inguinal folds (Figure 1, a, b). The initial diagnostic consideration was lymphoma. A biopsy specimen was taken, and the histopathological features revealed epidermal hyperplasia with papillomatosis, minimal spongiosis with many neutrophils and with a marked inflammatory infiltrate in dermis, consisting of lymphocytes, plasma cells, and neutrophils; the diagnosis of interfaced dermatitis was established (Figure 1, d, e). After one month, the patient presented to our clinic with numerous nodular lesions, some of them painful, located on the trunk and intertriginous folds, including the intergluteal cleft - the lesions in this area being suggestive of condylomata lata (Figure 1, c). The diagnosis of secondary syphilis was taken into consideration, and screening serum tests were performed and found reactive: a Venereal Diseases Research Laboratory (VDRL) titer of 1:64 and Treponema pallidum Hemaglutination Assay (TPHA) titer of 1:80. Hepatitis and anti-human immunodeficiency virus (HIV) antibodies serology was negative. The biopsy was repeated and showed the same histopathological changes. In addition, Warthin-Starry staining was performed, revealing the presence of some spiral micro-organisms in the dermis corresponding to Treponema pallidum (Figure 1, f). A diagnosis of secondary syphilis was established, and the patient was treated with benzathine penicillin G 2.4 million units by intramuscular injection once a week for 2 consecutive weeks. The skin lesions regressed within 1 month, and serological tests showed a VDRL titer of 1:8 3 months after treatment. The second patient was a homosexual male, 35 years old, diagnosed with HIV infection, stage B2. He presented with bone pain in the calves and forearms, with insidious onset. He also presented with an associated erythematous maculo-papular rash on the trunk and limbs and generalized lymphadenopathy (Figure 2, a, b). The tibial crest and radius were sensitive to palpation. A right leg radiography was performed, raising suspicion of osteoid osteoma. The CT scan excluded the diagnosis of osteoma; taking into account the epidemiological context, the diagnosis of syphilis was suspected. The diagnosis was confirmed by leg ultrasound examination (2D US) which showed thickening of the compact tibial bone associated with subperiosteal destructive and proliferative changes (Figure 2, c, d) and by serology for syphilis: the VDRL titer was 1:32 and the TPHA titer was 1:80. The patient was treated with benzathine penicillin 2.4 million units, once a week, for 2 consecutive weeks, with clinical improvement. Syphilis continues to be a serious public health problem worldwide, even if it is a controllable disease due to diagnostic tests and effective and accessible treatment. According to the World Health Organization in 2008, the estimated number of new cases of sexually transmitted diseases in adults with syphilis is 10.6 million cases (4). The cases presented in this paper were characterized by unusual manifestations, requiring good collaboration between the dermatologist and other specialties. In the first case, the diagnosis of secondary syphilis was confirmed by positive serological, clinical, and histopathological findings. The main differential diagnosis of nodular syphilis includes lymphoma, sarcoidosis, Kaposi's sarcoma, atypical mycobacteriosis, deep fungal infections, leprosy, tuberculosis, leishmaniasis, and lymphomatoid papulosis (5). Another important differential diagnosis is between secondary and tertiary syphilis, especially when ulcerating nodules are present. Tertiary syphilis is characterized by unilateral, deep ulcerating nodules with necrotizing granulomas (6). Bone involvement during syphilis is mainly represented by polyarthritis, synovitis, osteitis, and periostitis (7,8). Syphilitic periostitis is characterized by localized or diffuse pain, particularly during the night, which is relieved by movement. The skull, the shoulder girdle, and the long bones are the most common sites of involvement (9). In conclusion, we presented two different cases of secondary syphilis that contribute to the clinical experience of rare cases presented in the literature, raising the awareness of dermatologists and other specialists about less specific clinical aspects of syphilis.

Could oral cytomorphometry be of value in distinguishing diabetes mellitus?

The present study refers to a quantitative, morphometric analysis of exfoliative cytology smears collected from diabetes mellitus (DM) patients, in order to distinguish subtle changes in cellular and nuclear parameters. The study was carried out on 30 adult subjects: a control group of 10 healthy subjects and a study group of 20 diabetic subjects (type 1 and type 2 DM). Another factor that was taken into consideration was the abundance of the microbial flora. The oral smears were stained using Hematoxylin and Eosin and several parameters were measured (nuclear diameter, perimeter and area, cell large diameter and area), and calculated: nuclear/cytoplasmic ratio and nuclear roundness factor. We found out that the cells collected from DM patients had higher values of the nuclear parameters (the nuclei were larger) and lower cell dimensions. The nuclear to cytoplasmic ratio was increased in these patients, but the nuclear roundness factor was closer to one in the study group. Also, an increased number of bacteria, often seen in DM patients, decreased the nuclear parameters. Our findings complete recently descriptive cytology studies with the morphological measurements in case of bacterial abundance and sustain the possible value as screening method for morphometry.

Hemorrhagic polypoid gastric and colonic metastases nine years after uterine leiomyosarcoma - case report.

INTRODUCTION: Uterine leiomyosarcoma (ULMS) is a rare tumor, representing 1-2% of all uterine malignancies. It is highly aggressive, with high metastatic rate, especially in lungs, peritoneal cavity, retroperitoneum, bones and liver, usually during the first years after diagnosis. CASE PRESENTATION: A 58-year-old woman, with subtotal hysterectomy and bilateral adnexectomy, followed by radiochemotherapy for spindle-type ULMS nine years ago, presented with gastrointestinal bleeding and severe anemia. Three polyps ranging from 2 cm to 5 cm in diameter were found at gastroscopy, the largest being ulcerated, which required a total gastrectomy three months later. Colonoscopy identified two pedunculated polyps on the descending colon, 2 cm and 3.5 cm in diameter. Histologically, both sites revealed proliferations of spindle cells with whorled pattern, moderate to severe nuclear atypia, 5 to 8 mitotic figures (MFs)÷10 high-power fields (HPFs) and additional necrosis in the gastric tumors. Immunohistochemistry was negative for CD117, DOG1, S100 and CD34 and positive for smooth muscle actin (SMA), estrogen receptor (ER) and progesterone receptor (PR). Twenty percent of nuclei stained positive for Ki67. The diagnosis was synchronous hemorrhagic gastric and colonic polypoid metastases of ULMS. Thoracic computed tomography (CT) and abdominal ultrasonography were negative for other metastatic lesions, while abdominal CT revealed abdominal and pelvic lymphadenopathy. CONCLUSIONS: This case illustrates a distinct pattern of metastasis that is an extremely rare gastric and colonic location and an expanded disease-free period of nine years since the initial treatment. A long-term clinical and imaging follow-up of this patient is essential.

New insights into the cellular makeup and progenitor potential of palatal connective tissues.

The present study investigated the regenerative potential of connective tissues harvested from two palatal areas widely used as donor sites for muco-gingival surgical approaches. Connective tissue grafts (CTGs) were obtained by de-epithelialisation of a free gingival graft (deCTG) and by a split flap approach from a previous donor site (reCTG). Two types of mesenchymal stem cell (MSCs) were isolated and were named de-epithelialised MSCs (deMSCs) and re-entry MSCs (reMSCs). The cells were characterised and cellular functionality was investigated. CTGs were evaluated using immunohistochemical and ultrastructural approaches. No significant differences were observed regarding the frequency of colony-forming unit- fibroblasts, migration potential, and population doubling time between the two cell lines (p > 0.05). Both cell lines showed positivity for CD105, CD73, CD90, and CD44 and negative expression for CD34/45, CD14, CD79a, and HLA-DR. MSCs from both cell lines successfully differentiated into osteogenic, adipogenic, and chondrogenic lineages. Cells expressing antigens characteristic of CD34+ stromal cells (CD34+, αSMA-, CD31-) were traced in both CTGs. Ultrastructural analysis highlighted the presence of putative progenitors, namely fibroblasts,-in the pericapillary regions and in remote regions of the lamina propria- and pericytes-surrounding the capillaries. This study provides supplementary arguments for the use of CTG grafts in clinical practice due to the presence of putative progenitor cell. However, results were inconclusive regarding clinical decision-making to determine optimal harvesting area. Prior harvesting in the donor area did not appear to alter the regenerative capabilities of the connective tissue.

Keratoacanthoma of the conjunctiva - case report and review of the literature.

INTRODUCTION: Keratoacanthoma (KA) is a relatively common, benign, rapidly growing and self-limiting squamous proliferation, which appears most frequently on the sun-exposed skin. The nature of KA and its relationship to squamous cell carcinoma (SCC) still represent one of the major debates in dermatopathology, as it is the truthfulness of such a diagnosis outside the skin. However, the tumor is now known to originate from the pilosebaceous units of the skin or from ectopic sebaceous glands of squamous mucous membranes, and to differentiate onto follicular isthmus÷infundibulum-like epithelium. CASE PRESENTATION: A 71-year-old man presented with a sore and red right eye, which on slit-lamp biomicroscopical examination revealed a dome-shaped lesion at the temporal inferior conjunctival limbus. After a thorough histopathological examination, a diagnosis of KA has been made, both after the initial tumor excision and after the relatively rapid recurrence. After the second intervention, no recurrence was observed over five years of follow-up, confirming the diagnosis. CONCLUSIONS: The peculiarity of the case stands in his exceptional rarity, being to our knowledge the first conjunctival KA reported in our country. In the light of current knowledge, the peculiar limbal location of all the conjunctival KAs reported in the literature raised the question of the possible role of limbal stem cells in the histogenesis of these tumors, similar to the pilosebaceous ones. The treatment of conjunctival KA remains the complete excision of the tumor, as it allows histopathological evaluation of the entire tumor and the exclusion of a KA-like SCCs or KAs with SCC component.