Ciliated Cells in Renal Calyx mucosa: Metaplastic Change or Developmental Abnormality? Immunohistochemical Study of one Case and Review of the Literature.

Ciliated epithelial cells have been rarely observed in urothelium lined mucosa. Only extremely rare reports in the literature have described this phenomenon and no cases have been described in other sites than the male urethra. Herein, we illustrate the finding of ciliated pseudostratified columnar cells in the renal calyx mucosa adjacent to an area of urothelial invasive carcinoma in an 82 year-old man with previous history of nephrolithiasis. The ciliated cells covered a linear extension of 0.5 cm: they were positive for keratin 7 and keratin 8/18 and negative for keratin 20. Alcian blue staining was positive in some vacuoles in the apical cytoplasm of the same cells whereas PAS (Periodic Acid-Schiff) staining was negative. GATA3 resulted negative in ciliated cells except for a layer in the basal portion of the epithelium, just above the basal membrane. The actual prevalence of ciliated epithelia in the urinary tract is not well documented and the current knowledge on the subject is limited to electron scanning microscopy studies. The significance of this phenomenon remains unknown: it could be either a developmental abnormality or more probably a metaplastic change. Associated urolithiasis, which has been described in both a previous report and in the present one, could hypothetically represent a possible trigger for this unusual cell change. However, this hypothesis needs to be confirmed through further investigation.

Exploring Mitochondrial Localization of SARS-CoV-2 RNA by Padlock Assay: A Pilot Study in Human Placenta.

The ongoing COVID-19 pandemic dictated new priorities in biomedicine research. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, is a single-stranded positive-sense RNA virus. In this pilot study, we optimized our padlock assay to visualize genomic and subgenomic regions using formalin-fixed paraffin-embedded placental samples obtained from a confirmed case of COVID-19. SARS-CoV-2 RNA was localized in trophoblastic cells. We also checked the presence of the virion by immunolocalization of its glycoprotein spike. In addition, we imaged mitochondria of placental villi keeping in mind that the mitochondrion has been suggested as a potential residence of the SARS-CoV-2 genome. We observed a substantial overlapping of SARS-CoV-2 RNA and mitochondria in trophoblastic cells. This intriguing linkage correlated with an aberrant mitochondrial network. Overall, to the best of our knowledge, this is the first study that provides evidence of colocalization of the SARS-CoV-2 genome and mitochondria in SARS-CoV-2 infected tissue. These findings also support the notion that SARS-CoV-2 infection can reprogram mitochondrial activity in the highly specialized maternal-fetal interface.

In Vivo Comparison of Micro-Balloon Interventions (MBI) Advantage: A Retrospective Cohort Study of DEB-TACE Versus b-TACE and of SIRT Versus b-SIRT.

PURPOSE: The purpose of this study was to evaluate in vivo the role of the micro-balloon by comparing trans-arterial chemoembolization (DEB-TACE) and selective internal radiotherapy (SIRT) procedures performed with and without balloon micro-catheter (b-DEB-TACE and DEB-TACE/SIRT and b-SIRT) for the treatment of hepatocellular carcinoma (HCC). METHODS: The impact of a balloon micro-catheter on trans-arterial loco-regional treatment was analyzed using non-enhanced post-procedural cone-beam CT (Ne-CBCT) by comparing the attenuation values in the embolized area and the surrounding liver tissue before and after DEB-TACE versus b-DEB-TACE and by comparing 2D/3D dosimetry in single-photon emission computed tomography after SIRT versus b-SIRT, and by comparing the histological count of the beads following orthotopic liver transplantation in the DEB-TACE versus b-DEB-TACE subgroup. RESULTS: We treated 84 HCC patients using trans-arterial loco-regional therapy. Fifty-three patients (26 DEB-TACE and 27 b-DEB-TACE) were analyzed in the TACE group. Contrast, signal-to-noise ratio, and contrast-to-noise ratio were all significantly higher in b-DEB-TACE subgroup than DEB-TACE (182.33 HU [CI95% 160.3-273.5] vs. 124 HU [CI95% 80.6-163.6]; 8.3 [CI95% 5.7-10.1] vs. 4.5 [CI95% 3.7-6.0]; 6.9 [CI95% 4.3-7.8] vs. 3.1 [CI95% 2.2-5.0] p < 0.05). Thirty-one patients (24 SIRT and 7 b-SIRT) were analyzed in the SIRT group. 2D dosimetry profile evaluation showed an activity intensity peak significantly higher in the b-SIRT than in the SIRT subgroup (987.5 ± 393.8 vs. 567.7 ± 302.2, p = 0.005). Regarding 3D dose analysis, the mean dose administered to the treated lesions was significantly higher in the b-SIRT than in the SIRT group (151.6 Gy ± 53.2 vs. 100.1 Gy ± 43.4, p = 0.01). In histological explanted liver analysis, there was a trend for higher intra-tumoral localization of embolic microspheres for b-DEB-TACE in comparison with DEB-TACE. CONCLUSIONS: Due to the use of three different methods, the results of this study demonstrate in vivo, a better embolization profile of oncological intra-arterial interventions performed with balloon micro-catheter regardless of the embolic agent employed.

Prostatic tissue: an unexpected finding in a mature ovarian teratoma : Case report and systematic literature review.

PURPOSE: Prostatic tissue in an ovarian teratoma is an unusual finding, whose initiation in a 46, XX karyotype tissue is yet to be clarified. We present a case from our files and review the literature for this intriguing finding. METHODS: Unstained histology sections of the ovarian teratoma containing prostatic tissue were evaluated using immunohistochemistry for PSA and androgen receptor. RESULTS: Both PSA and androgen receptor immunostainings were positive in the prostatic tissue. From the literature review, it appears that most of the patients (74%) with similar findings were either pregnant or experiencing a miscarriage, menopausal or infertile at presentation, showing that an imbalanced hormone status is frequently associated with the presence of male structures in ovarian teratomas.

Is Gastric Involvement by Strongyloides stercoralis in an Immunocompetent Patient a Common Finding? A Case Report and Review of the Literature.

PURPOSE: Gastric infection with Strongyloides stercoralis (SS) usually occurs in immunocompromised patients. The unexpected observation of this parasite in an otherwise healthy young lady who had undergone upper endoscopy and biopsy sampling of the gastro-duodenal mucosa, prompted us to review the literature to ascertain the conditions favouring gastric colonization by SS. METHODS: Pathology files of gastroduodenal biopsies received at St. Mary's hospital, Northern Uganda, between 2007 and 2017 were reviewed. Pubmed search was performed under the headings "Strongyloides stercoralis", "Gastric parasitosis". RESULTS: Histology of the only gastroduodenal biopsy with SS infection showed parasite eggs, immature rhabditiform larvae, and numerous adult worms in gastric pits and rhabditiform larvae in interepithelial parasitic tunnels, causing reactive changes of the glandular epithelium. There was no significant acute inflammatory cell infiltrate surrounding the parasites. Literature review showed that gastric SS infection appears to be very uncommon and was, as expected, largely prevalent in immunodeficient individuals (84.2% of published cases). The rare gastric SS infection is a complication of systemic strongyloidiasis, either hyperinfective, or disseminated form. It is also commonly associated with duodenal infection at microscopical examination. CONCLUSION: Involvement of gastric mucosa in the absence of duodenal strongyloidiasis appears to be quite rare and false-negative histopathological exams are reported if only the stomach is biopsied.

Primary anaplastic large T-cell lymphoma of the psoas muscle.

Lymphomas presenting and mimicking soft-tissue masses are important to recognize, to avoid unnecessary treatment delays or extensive surgery. We describe a case of primary anaplastic large cell lymphoma (ALCL) arising from a deep skeletal muscle in a middle-aged male. He presented with a two-month history of swelling of his right thigh and mild fever, which led to a diagnosis of abscess formation. Antibiotics were prescribed for two weeks, with little improvement of symptoms. Subsequently, an exploratory surgery, with excision of the mass, demonstrated a ALCL of the psoas muscle, ALK-1 positive.

Incidence of male breast carcinoma in North Uganda: A survey at Lacor Hospital, Gulu, during 2009-2016.

BACKGROUND: Little information is available on male breast cancer (MBC) incidence from sub-Saharan Africa. OBJECTIVE: This is a retrospective study on MBC in rural North Uganda, based on the pathology records of a private, non-profit, missionary hospital. METHODS: All male patients that had histological diagnosis of breast carcinoma from January 2009 to December 2016 were included in this study. RESULTS: In time span of 8 years, there were 337 consecutive breast cancer presentations, including 21 MBC (6.2%). The latter patients showed advanced disease (mean symptom duration: 20.3 months; mean tumour size: 5 cm) skin ulceration and ipsilateral lymph node metastasis: 60%). The mean age was 60.52 years (from 30 to 85 yrs). Ductal infiltrating carcinoma was the prevalent histological type in our series (65%), followed by an unusually high rate of papillary carcinomas (15%). There appeared to be a prevalence for left breasts (11 LT versus 6 RT; 64.7%), a finding also observed in the majority of MBC. CONCLUSIONS: This study is representative of the scenario in Northern Uganda, where MBC accounts for 6.2% of breast cancers, More information on the occurrence and risk factors of this unusual neoplasm in African countries may prompt prevention of chronic liver disease and early recognition and treatment of MBC.

Zero-ischemia testis-sparing surgery for probably benign pediatric testicular tumors.

Permanent ischemia-induced testicular damage may occur as early as 30 min in prepupertal rats. With the goal of potentially enhancing testicular function and fertility preservation, we performed testis-sparing surgery (TSS) without ischemia for testicular lesions in select children with negative markers and high likelihood of benignity on ultrasonography. Preliminary experience suggests that off-clamp TSS should be more liberally encouraged, especially in infants and prepubertal children, given their particularly vulnerable spermatic cord elements.

PD-L1 expression is associated with tumor infiltrating lymphocytes that predict response to NACT in squamous cell cervical cancer.

Cancer immunotherapy has significantly improved the management of many malignancies in recent years. Although cervical cancer is the second most common women's cancer in the world, there are still few information about the role of checkpoint inhibitors in this neoplasm, especially in the neoadjuvant setting. In the present study, we retrieved 38 consecutive patients with squamous cell cervical cancer who underwent platinum-based neoadjuvant chemotherapy (NACT) followed by radical surgery. Pre-therapy biopsies were evaluated for the presence of tumor-infiltrating lymphocytes (TILs), including T (both cytotoxic CD8+ and helper CD4+) and B lymphocytes, macrophages, natural-killer cells, and eosinophils. Immunohistochemistry was performed to characterize the inflammatory cells and to evaluate programmed death-ligand 1 (PD-L1) expression on both neoplastic and inflammatory cells. We divided our study population in three groups using three cut-offs (< 10%, 10-40%, >40%), for both TILs and PD-L1 evaluation. Pathological response to NACT was obtained from the histological reports of the post-therapy surgical specimens. We observed that all cases showed stromal TILs, with a predominance of CD3+/CD4+ T helper cells, thus supporting the strong immunogenic potential of cervical cancer. The vast majority of neoplasms expressed PD-L1: 100% on immune cells and 92% on tumor cells. Firstly, we noticed that the percentage of neoplastic cells PD-L1+ was positively associated with high TIL percentage (p = 0.0073) and with increased PD-L1 expression on inflammatory cells (p = 0.0297). Secondly, we observed a significant correlation between both the percentage (p = 0.0105) of TILs and the expression of PD-L1 (p = 0.01045) on inflammatory cells and pathological response to NACT. These results suggest that cervical cancer could be a good target for immunotherapy, also in the neoadjuvant setting. Furthermore, PD-L1 expression was significantly associated with stromal TILs that interestingly may predict pathological response to NACT.

CTNNB1 p.L31P mutation in an ovarian endometrioid carcinoma with synchronous uterine endometrioid carcinoma.

We performed next generation sequencing of DNA extracted from the neoplastic tissues obtained from a patient who underwent surgery for a large right ovarian carcinoma (OC) of endometrioid type associated with endometrial cancer (EC). This was done in order to ascertain whether the tumors were synchronous endometrial/ovarian cancers or an advanced metastatic stage from either the ovary or the uterus. Pathologic criteria favoured synchronous EC/OC. We identified a PTEN c.959 T > G (p.L320X) truncating mutation occurring with similar allele frequency in both neoplastic tissues (ovary: 88 %, endometrium 89 %) and a CTNNB1 c.100C > G (p.S37C) activating mutation, with a comparable allelic frequency in both tumor tissues (ovary 51 %, endometrium 52 %). The shared genetic mutations, and the presence of PTEN c.959 T > G (p.L320X) truncating mutation, albeit at low allelic frequency (6 %), in the healthy peritumoral endometrial tissue, appear to confirm the recent literature on a primary endometrial origin for synchronous EC/OC. A third mutation was CTNNB1 c.92 T > C (p.L31 P), a missense mutation occurring with a low allele frequency (3.7 %) only in the ovarian cancer tissue. This mutation is only occasionally described in hepatocellular carcinomas.

Immunohistochemical detection of IL-17 and IL-23 improves the identification of patients with a possible diagnosis of Sjogren's syndrome.

OBJECTIVES: The diagnosis of primary Sjogren's syndrome (pSS) continues to be difficult and several patients keep symptomatic for years with different diagnoses before confirmation of pSS. Since the IL-23-IL-17 axis is involved in the etiopathogenesis of pSS we evaluated by immunohistochemistry and morphometric methods the presence of IL-17 as well as IL-23 within minor salivary glands (MSG) obtained from patients with uncertain diagnosis of pSS. MATERIALS AND METHODS: 42 patients, with symptoms attributable to pSS, and 8 patients used as a control, were enrolled for the study. Autoantibody detection, histological analysis for the presence of Germinal Centers (GC+), immunohistochemistry to detect IL-23 and IL-17 were performed. RESULTS: The detection of GC + anti-SSA and anti-SSB antibody in parallel with the detection of IL-17 and IL-23, displays only a diagnostic reinforcement value. Instead, the detection of a positive reaction for both IL-17 and IL-23 without GC + or autoantibody within minor salivary glands, as detected in 36 % of patients with uncertain diagnosis, may be hold as a sensitive and specific marker to identify those patients who are likely to evolve into pSS. CONCLUSION: we suggest to use the IL-17/ IL-23 immunohistochemical detection to improve the identification of patients with a possible diagnosis in all cases which do not fully meet the American-European criteria for pSS, in particular when the GC + are not present at histopathological analysis and anti-SSA and anti-SSB antibody are undetectable in the serum.

Protein Induced by Vitamin K Absence II (PIVKA-II) as a potential serological biomarker in pancreatic cancer: a pilot study.

INTRODUCTION: Protein induced by vitamin K absence II (PIVKA-II) is an abnormal prothrombin increased in gastrointestinal malignancy. We aimed to evaluate PIVKA-II in comparison to established pancreatic cancer (PC) biomarkers (CA 19-9, carcinoembryonic antigen (CEA) and CA 242) measured in PC patients and in patients with benign pancreatic diseases. MATERIALS AND METHODS: We studied 26 PC patients (Group 1) and 20 patients with benign pancreatic diseases (Group 2). PIVKA-II and CEA were measured by chemiluminescent enzyme immunoassay method (CLEIA) on LUMIPULSE G1200 (Fujirebio-Europe, Gent, Belgium), CA 19-9 and CA 242 were measured by ELSA (CisBio Bioassays, Codolet, France) and EIA (Fujirebio Diagnostics AB, Göteborg, Sweden), respectively. Receiver operating characteristic (ROC) analysis was performed to assess biomarkers' diagnostic characteristics in both groups. RESULTS: Median and interquartile range (IQR) in Group 1 and Group 2 were: 1749.0 (320.2 - 3921.0) vs. 31.0 (23.0 - 43.0) mAU/mL (P < 0.001) for PIVKA-II, 260.0 (158.7 - 272.0) vs. 45.2 (9.0 - 58.0) U/mL (P = 0.034) for CA 19-9, 104.0 (30.2 - 150.0) vs. 7.2 (4.8 - 26.0) U/mL (P < 0.050) for CA 242, 9.4 (5.3 - 37.5) vs. 4.5 (1.8 - 7.0) ng/mL (P = 0.021) for CEA. Areas under the ROC curve of PIVKA-II, CA 19-9, CA 242, CEA were 0.86 (95% CI: 0.71 - 1.00), 0.58 (95% CI: 0.38 - 0.78), 0.73 (95% CI: 0.54 - 0.92), 0.64 (95% CI: 0.44 - 0.85), respectively. CONCLUSIONS: PIVKA-II is significantly higher in PC than in benign pancreatic diseases. PIVKA-II shows a rather good diagnostic performance compared to CA 19-9, CEA and CA242, thus its determination could help PC management.

Ovarian Reserve Reduction With Surgery Is Not Correlated With the Amount of Ovarian Tissue Inadvertently Excised at Laparoscopic Surgery for Endometriomas.

The aim of the present study was to evaluate the effect of laparoscopic cystectomy on ovarian reserve by means of anti-Müllerian hormone (AMH) serial measurements and to compare AMH values with the number of inadvertently removed follicles in histological specimens. Fifty-two women were enrolled: 34 patients with endometriomas (group 1) and 18 patients with other benign ovarian cysts (group 2). All patients underwent laparoscopic cystectomy performed by a single experienced surgeon. The AMH was measured before, and 1, 3, and 6 months after cystectomy in group 1, and before and 6 months after surgery in group 2. Preoperative AMH levels (mean [standard deviation, SD]) in group 1 (3.39 [2.43] ng/mL) were not significantly different from group 2 (3.74 [2.57] ng/mL; P = .68). In group 1, a significant decrease in AMH levels of 43.4% was observed at 1 month (1.93 [1.36]; P = .003), and of 63.1% at 3 months (1.25 [1.00]; P = .007) postoperatively. The AMH increased not significantly between the third and sixth months in group 1 (+9.4%). Six months after surgery, AMH was reduced by 59.3% compared to baseline values in group 1 (P = .012), and by 29.5% in group 2 (P = .200). A significant difference in the AMH decrease was present between bilateral and monolateral endometriomas (P = .006). There was no correlation between the reduction rate of AMH and the number of follicles inadvertently removed in patients with endometriomas (P = .669). In conclusion, AMH decreases significantly after surgical excision of ovarian endometriomas. The postoperative decrease does not appear to correlate with the amount of ovarian tissue inadvertently excised with the endometrioma wall.

Metastases to extraocular muscles from breast cancer: case report and up-to-date review of the literature.

BACKGROUND: Unilateral or bilateral metastases to extraocular muscles are very rare in breast cancer. CASE PRESENTATION: We describe a case of inferior rectus extraocular muscle involved by ductal luminal B/Her-2 neu negative breast cancer, observed in a cohort of 580 patients. Our patient had received chemotherapy and hormonal therapy (tamoxifen for 3 years and letrozole in the following 3 years) for her primary cancer and developed an orbital metastasis while she was under aromatase inhibitor-based therapy. Diagnosis was confirmed by MRI and biopsy. Orbital radiotherapy, combined with fulvestrant, resulted in shrinking of the secondary mass. A third line hormonal therapy using palbociclib was then started. Twelve-months later, MRI showed no residual tumor mass. Currently, the patient is alive and in good general conditions after 20 months. CONCLUSIONS: Literature review yielded 57 patients with extraocular muscle metastases from breast cancer, mostly due to the invasive lobular subtype of carcinoma. In addition to the present case, only 4 other extraocular muscles metastases from invasive ductal carcinoma has been reported, pointing out to the rarity of ductal type spread to the orbit in the natural history of breast cancer. Surgery may be used as a single treatment, despite no improvement of symptoms. Radiotherapy alone or combined with chemotherapy, or with chemotherapy plus hormonal therapy are available options. Results are, however, missing or poor. The present case is the first one with complete and stable response after 20 months to radiotherapy, antiestrogen drug fulvestrant and selective inhibitor of CDK4 /CDK6 palbociclib. In this subset of patients, with unusual metastatic sites and frequent multi-organ metastatic impairment, a multidisciplinary approach is indicated in order to achieve the best therapeutic management and long-term surveillance.

Polyp of the uterine cervix with heterologous fatty tissue.

This report documents an uncommon case of choristomatous cervical polyp-containing fat tissue. The patient was a 24-year-old female who presented with irregular intermenstrual bleeding. On examination, a polypoid lesion with smooth outlines, measuring 1 cm in diameter was removed. Microscopic examination demonstrated abnormal fibrous stroma, devoid of endocervical glands, containing mature adipose tissue, and thick-walled blood vessels. The lesion was covered by a typical mature squamous cell outer lining. To the best of our knowledge, this is only the second report of an adipose tissue arising from the cervical wall. Further clinicopathologic considerations are needed to elucidate the origin of the fatty component in cervical polyps.

Impact of Hormone Receptor Status and Ki-67 Expression on Disease-Free Survival in Patients Affected by High-risk Endometrial Cancer.

OBJECTIVES: The aim of this study was to evaluate the immunohistochemical (IHC) expression of Ki-67, estrogen receptors α (ERsα), and progesterone receptors (PRs) in high-risk endometrial cancer patients and to assess their prognostic impact. METHODS/MATERIALS: Immunohistochemical expression of Ki-67, ERsα, and PRs was evaluated in primary untreated endometrial cancer. The correlation among IHC staining and risk factors of recurrence such as age, Federation International of Gynecology and Obstetrics stage, grading, depth of invasion, and metastatic spread was assessed. RESULTS: Eighty-two patients were available for the analysis. Mean ± SD age was 65.05 ± 10.48 years. The IHC assessment revealed a lack of ERα in 46.3% and of PR in 48.7% as well as a high Ki-67 in 31.7%. Loss of ERα and PR was associated with a significant higher rate of advanced stage of disease, a higher frequency of G3 tumors, and a myometrial invasion greater than 50%. A strong Ki-67 expression correlated with a deeper myometrial invasion. Analysis of the interrelationship between receptor immunonegativity revealed a relevant association of ERα immunolocalization with PR and with a high Ki-67 expression. The present study also showed that loss of ERα (P = 0.003), advanced Federation International of Gynecology and Obstetrics stage (P < 0.001), and high Ki-67 (P = 0.004) were independent prognostic factors of a shorter disease-free survival. Importantly, loss of ERα, loss of PR, and a high Ki-67 were correlated with a higher incidence of distant recurrence. CONCLUSIONS: A systematic immunohistochemistry should be a key step in the therapeutic algorithm and could contribute to the identification of high-risk tumors.

HPV-related vulvar diseases and perspectives of p16INK4a immunochemistry: a review of the literature.

INTRODUCTION: Two different types of vulvar intraepithelial neoplasia (VIN), HPV-related and HPV-unrelated, should be considered as two separate entities with different management options. The incidence of HPV-related VIN is increasing worldwide and is implicated in carcinogenesis. Our objective is to investigate the use of p16INK4a immunostaining or p16INK4a/p53 double staining for the detection of HPV-related disease to overcome the problem that histological criteria often have significant overlap. METHODS: A systematic literature search was carried out in the online databases PubMed, EMBASE, Cochrane Library, Clincaltrials.gov and Scopus. The key search terms were HPV, VIN, p16INK4a immunochemistry and p53. RESULTS: We found that nuclear and cytoplasmic immunostaining for p16INK4a was intense and diffuse in HPV-associated lesions and weak and focal in normal vulvar epithelium, nondysplastic lesions, lichen sclerosus and keratinizing vulvar squamous cell carcinoma. p53 nuclear immunostaining was always negative in HPV-related disease. CONCLUSIONS: Our findings indicated that p16INK4a or p16INK4a/p53 immunoreactivity, along with histological diagnosis, could be a convenient means to adequately classify VIN and its connection to HPV infection. Therefore, the clear recognition of HPV-associated VIN would lead to an appropriate strategy of treatment and follow-up.

Vitamin D levels in children affected by vernal keratoconjunctivitis.

BACKGROUND: Vernal keratoconjunctivitis (VKC) is a chronic and often severe bilateral conjunctivitis. VKC etiology still remains unclear although endocrine, genetic, neurogenic and environmental factors have been implicated. Vitamin D is a fat-soluble prohormone whose main function is the regulation of calcium and phosphate metabolism. The aim of this study was to evaluate serum vitamin D in children affected by VKC compared to the healthy children and investigate the relationship between its levels and disease severity. METHODS: A total of 110 children, 47 affected by VKC, aged between 5 and 12 years were enrolled at the Department of Pediatrics, Division of Allergy and Immunology, "Sapienza" University of Rome. Used as controls were 63 healthy children with negative skin prick test (SPT), without allergic, ocular and systemic disease. Serum samples were obtained in April from all the children included in the study. Vitamin D dosage was repeated in October in 20 patients after therapy and in 20 controls. A conjunctival scraping was performed in all children affected by VKC. RESULTS: Children affected by VKC had lower vitamin D levels compared to healthy controls and we found an increase in vitamin D levels after therapy with cyclosporine eye drops 1% although this increase was lower than that of healthy controls. Moreover we found significant correlations between vitamin D level and the severity of the disease. CONCLUSIONS: The study shows that children affected by VKC have lower vitamin D levels when compared to healthy controls and highlights a significant correlation between its levels and disease severity.