Search Results (24)

Background: Intestinal-type vulvar adenocarcinoma (VAIt) is an exceptionally rare form of primary vulvar cancer, characterized by histological features resembling mucinous colonic carcinomas, including villo-glandular structures composed of goblet and Paneth cells with intracytoplasmic mucin. Objective: To provide a comprehensive synthesis of the existing literature on VAIt and to also report a case from our institution in order to define its clinical, pathological, and immunohistochemical characteristics and its management and prognosis. Materials and Methods: A systematic review of the literature according to PRISMA guidelines was performed through searching five electronic databases (MEDLINE, EMBASE, Web of Science, SCOPUS and Cochrane Library), considering studies from 1998 to May 2025. In our research, we included all peer-reviewed studies which reported cases of VAIt. Data about VAIt were extracted by included studies and compared. Results: All in all, 32 studies with a total of 40 cases (including our case) of VAIt were assessed. The median age at diagnosis was 58 years. Most tumors arose in the labia or perineal structures, often mimicking benign lesions. Immunohistochemistry consistently showed CK20 and CDX2 positivity, with variable CK7 and p16 expression. FIGO stage IA was the most frequent stage at diagnosis. Surgical excision was the mainstay of treatment, while adjuvant therapy was less commonly reported. Lymph node metastases were present in about 31.5% of cases. Despite aggressive histology, most patients were disease-free at follow-up. Mortality due to disease occurred in 10% of cases. Conclusions: VAIt is a very rare histotype of vulvar cancer. Compared to vulvar squamous cell carcinomas, approximately 40% of early-stage clinical diseases reported in the literature presented positive inguinal lymph nodes with recurrence even after many years. The optimal treatment is not well defined and should be based on the individual clinical history of the patient, as there are no established guidelines. Further studies and longer follow-up periods are needed to clarify the best therapeutic management and its long-term prognosis. Full article

Background/Objectives: Eyelid malignancies represent a clinically relevant subset of cutaneous tumors of the head and neck, with significant functional and cosmetic implications. While basal cell carcinoma (BCC) is the predominant subtype, geographic differences in the relative frequency of squamous cell carcinoma (SCC) and rarer histotypes have been reported. This study aimed at comparing the distribution of malignant eyelid tumors diagnosed in two Italian referral centers, namely Cagliari (Sardinia) and Milan (Lombardy) between 2020 and 2024, and to explore demographic and epidemiologic correlates. Methods: A total of 250 malignant eyelid tumors were analyzed: 130 from Cagliari and 120 from Milan. BCC was the most common histological subtype overall (83.2%), followed by SCC (12.4%) and other malignancies (4.4%). The proportion of SCC was significantly higher in Milan (18.3%) compared to Cagliari (6.9%, p = 0.04). Logistic regression confirmed Milan as an independent risk factor for SCC (OR 3.79; 95% CI 1.57–9.18; p = 0.003). Male gender also emerged as a predictor of SCC (OR 2.50; 95% CI 1.10–5.67; p = 0.029). Most cases occurred in patients ≥70 years; cases under 50 years were rare (≈3%). Conclusions: BCC remains the predominant malignant eyelid tumor in Italy; significant inter-regional variability exists, with a higher proportion of SCC in northern Italy. These findings highlight the role of environmental, demographic, and organizational factors, and emphasize the need for multicenter registries. Region-specific insights may inform personalized prevention and surveillance strategies for eyelid malignancies. These findings may support the development of region-tailored prevention models and contribute to the growing field of personalized oncology within ophthalmology. Full article

Bartholin gland carcinoma (BGC) is a rare malignancy, comprising 3–7% of vulvar cancers and <1% of gynecologic tumors. Due to its low incidence, high-level evidence is lacking, and management is largely extrapolated from vulvar cancer guidelines. This comprehensive narrative review synthesizes current evidence on BGC, emphasizing histotype-specific features, diagnostic criteria, molecular profiling, and treatment strategies. The three most common subtypes are squamous cell carcinoma, adenoid cystic carcinoma (AdCC), and adenocarcinoma. HPV-associated tumors tend to occur in younger women and carry favorable prognoses. Accurate diagnosis requires exclusion of metastases and integration of clinical, imaging, and immunohistochemical data, including p16/HPV for squamous tumors, MYB/MYBL1 fusions for AdCC, and CK20/CDX2/SATB2 for intestinal-type adenocarcinoma. Approximately 50% of cases are diagnosed at an advanced stage due to misclassification as benign cysts or abscesses. Nodal metastasis occurs in >40% of cases, with histotype influencing prognosis. Adenocarcinoma and node-positive disease independently predict worse survival. Treatment hinges on complete surgical excision with 2–3 mm margins, bilateral groin evaluation, and histology-tailored adjuvant therapy. Emerging data support the use of immune checkpoint inhibitors in squamous BGC and targeted agents (e.g., mTOR/CDK4/6 inhibitors) in adenocarcinoma. We propose a practical molecular testing algorithm and highlight the urgent need for prospective, multinational collaboration to establish BGC-specific guidelines. Full article

Episiotomy is a perineal incision enlarging the vaginal opening during labor, preventing severe perineal/vaginal/ano-rectal lacerations. We performed a systematic literature review (PRISMA guidelines; Pubmed, Scopus and Web of Science databases) of primary malignant tumors arising from the episiotomy site. Thirteen primary carcinomas were reported, mainly endometriosis-related histotypes (77%) (nine clear cell, CCC; one endometrioid, EC) with only two vulvar invasive squamous cell carcinomas and one adenoid cystic carcinoma of Bartholin’s gland. No sarcomas, melanomas or malignant trophoblastic tumors were described. Endometriosis was associated with tumors or reported in history (62%). Malignant transformation occurred 3 to 27 (mean 16) years after diagnosis of endometriosis. Patients were usually post-/peri-menopausal (eight cases, 61%) (age range: 31–70 years, mean 50). Imaging should exclude distant (0% in our series) or lymph node metastases (three cases, 23%), looking for potential invasion of vagina (five cases, 39%), anus (including sphincter) (four cases, 31%) and/or other deep pelvic soft tissues (five cases, 39%). All patients underwent surgery, except for a CCC-patient (only chemoradiation) subsequently progressing and dying of disease. Adjuvant chemotherapy and/or radiotherapy were administered to five (39%) cases, neoadjuvant therapy to four cases (31%). Globally, three (23%) cases recurred or progressed, and two-thirds (15%) died of disease (1 CCC, 1 EC). Radical surgery with lymph node status evaluation and eventual excision should be performed when possible. Chemotherapy and/or radiotherapy can be considered in an adjuvant and/or neoadjuvant setting (or as only treatment in inoperable patients). However, the role of different treatments should be studied in further larger multicenter series. Full article

The present study investigates the impact of the COVID-19 pandemic on the management of Non-Melanoma Skin Cancer (NMSC) in the head and neck region. Conducted at the University Hospital “Le Scotte” in Siena, Italy, the research includes 111 patients treated from 2018 to 2021. The study aims to understand how pandemic-related healthcare changes affected NMSC treatment, focusing on differences in diagnosis and management before and during the pandemic. Methods involved retrospective analysis of patient demographics, clinical characteristics, lesion details, and treatment modalities, using Jamovi software (version 1.6) for statistical analysis. Results revealed the scalp as the most common NMSC site, with Squamous Cell Carcinoma (SCC) being the predominant histotype. A significant rise in Basal Cell Carcinoma (BCC) cases and a reduction in surgery duration were noted during the pandemic. The shift to local anesthesia was more pronounced, reflecting the necessity to adapt to healthcare limitations. Despite the disruptions caused by the pandemic, there was no significant drop in NMSC cases, which is attributed to the noticeable nature of head and neck lesions. In conclusion, this study highlights that the COVID-19 pandemic significantly influenced surgical practices in NMSC management, emphasizing the need for effective healthcare strategies that balance quality patient care with public health safety measures. Full article

Sex is a biological variable that can reflect clinical outcomes in terms of quality of life, therapy effectiveness, responsiveness and/or toxicity. Sphingosine-1-phosphate (S1P) is a lipidic mediator whose activity can be influenced by sex. To evaluate whether the S1P axis underlies sex ‘instructions’ in the lung during physiological and oncological lung conditions, sphingosine and S1P were quantified in the blood of healthy (H) volunteers, lung adenocarcinoma (ADK) and squamous cell carcinoma (SCC) patients of both sexes. S1P receptors and their metabolic enzymes were evaluated in the tissues. Circulating levels of S1P were similar among H female and male subjects and female SCC patients. Instead, male and female ADK patients had lower circulating S1P levels. S1P receptor 3 (S1PR3) was physiologically expressed in the lung, but it was overexpressed in male SCC, and female and male ADK, but not in female SCC patients, who showed a significantly reduced ceramide synthase 1 (CERS1) mRNA and an overexpression of the ceramidase (ASAH1) precursor in lung tumor tissues, compared to male SCC and both male and female ADK patients. These findings highlighted sex differences in S1P rheostat in pathological conditions, but not in physiological conditions, identifying S1P as a prognostic mediator depending on lung cancer histotype. Full article

This study assessed the incidence, mortality, and survival of lung cancer subtypes of NSCSLC (non-small-cell lung cancer), SCLC (small-cell lung cancer), and other morphologies. It is an observational epidemiological study using 7197 cases from the Reggio Emilia Cancer Registry recorded between 2001 and 2020 in males and females. The incidence of NSCLC in 5104 males indicates a significant 3% annual increase until 2013 and then a decline of −3.2% that is not statistically significant; until 2014, mortality increased significantly (3.2%), but it then decreased non-significantly (−12.1%), especially squamous cell cancer. In 2093 females, the incidence and mortality trends continued to rise significantly through 2012, and then they began to slightly decline (not statistically significant). The two-year relative survival of NSCLC increased from 32% to 38% in males and from 42% to 56% in females. SCLC in males decreased significantly both in incidence and mortality, while in women, it showed a slight increase (significantly for incidence but not for mortality). This study is important because it analyzes the decrease in lung cancer in males and the increase in females in relation to the different histotypes. Our study’s findings confirmed a decline in male incidence and death beginning in 2013. We were unable to determine if the drop in cigarette smoking and the introduction of new drugs such as EGFR in first-line therapy were responsible for the lower incidence. Full article

Lung cancer is the leading cause of cancer deaths worldwide, and squamous cell carcinoma (SQC) is Taiwan’s second most common lung carcinoma histotype. This study aimed to investigate changes in the long-term trend of the SQC incidence rate in Taiwan. SQC cases between 1985 and 2019 were adopted from Taiwan‘s Cancer Registry System; the age-adjusted incidence rate was calculated using the World Standard Population in 2000. The long-term trends of the age, period, and birth cohort effect of SQC incidence rates were estimated using the SEER Age-Period-Cohort Web Tool. The results revealed that the incidence of lung carcinoma in Taiwan increased, while the incidence of SQC exhibited a slight decrease during this study period. The age rate ratio (ARR) of the incidence rate in men declined gradually, and the period effect changed more slowly for women than men. The cohort effect formed a bimodal curve. The annual percentage change results for women indicated that the ARR decreased from 1.652 (95% confidence interval (CI): 1.422, 1.9192) at 30 to 34 years to 0.559 (95% CI: 0.4988, 0.6265) at 75 to 79 years; the period effect decreased from 1.2204 (95% CI: 1.1148, 1.336) in 1995 to 1999 to 0.608 (95% CI: 0.5515, 0.6704) in 2015 to 2019, with a greater decline in the later period. The cohort effect was unimodal, with the SQC risk value peaking in the 1915 birth cohort and exhibiting a steady decline thereafter. The results of this study suggest that a decrease in the smoking rate may be the reason for the decline in the incidence of SQC, and we observed a similar trend between SQC and the smoking rate in men. Full article

Pilomatrix-like high-grade endometrioid carcinoma (PiMHEC) has recently been described as an aggressive variant of endometrial carcinoma. Herein, we described a case of ovarian PiMHEC, comparing it to endometrial PiMHEC and assessing previously published cases of putative ovarian PiMHEC. A 65-year-old woman underwent hysterectomy for an ovarian tumor characterized by solid nests of basaloid cells with prominent ghost cell keratinization. Immunohistochemistry showed nuclear β-catenin and CDX2 expression and loss of estrogen and progesterone receptors and PAX8. These features were consistently observed in all previously published cases and may represent diagnostic criteria of PiMHEC. Other frequent features were geographic necrosis and a low-grade endometrioid component. CK7, neuroendocrine, and basal/squamous markers were inconsistently expressed. All cases with available follow-up showed poor prognosis. PiMHEC should be distinguished from mimickers, such as high-grade endometrioid carcinoma with geographic necrosis, low-grade endometrioid carcinoma with ghost cell keratinization, and undifferentiated/dedifferentiated carcinoma. In conclusion, PiMHEC can also occur in the ovary and shows several consistent clinical, morphological, and immunophenotypical features. These features support that PiMHEC is a distinct entity requiring an aggressive management. Full article

Objective: Worldwide cervical cancer is the fourth most common cancer and is also the fourth leading cause of death among women, after breast cancer, colorectal cancer, and lung cancer. The aim of this study is to investigate the long-term oncological safety of laparoscopic treatment without the use of a uterine manipulator for patients with early stage cervical cancer. Materials and methods: A single-center retrospective study was conducted at the Department of Obstetrics and Gynecology of ARNAS Garibaldi Nesima on patients surgically treated for early cervical cancer from 2014 to 2017. Inclusion criteria included squamous or adenosquamous histotype, FIGO stage from Ia1 to Ib2, cancer size < 4 cm, ECOG status 0–1, and negative serum beta-HCG. The patients were divided into two groups: treatment with and without an intra-uterine manipulator. Results: Seventy patients were identified, but only thirty-one met the inclusion criteria and were enrolled. All patients underwent surgery: three patients with the uterine manipulator, twenty-eight without. Among the thirty-one patients enrolled, twelve women had cancer in situ (IA1), nineteen had an early stage cervical cancer, in particular two cases of cervical cancer stage IA2, ten cases of cervical cancer stage IB1, and seven cases of cervical cancer stage IB2, according to the FIGO classification. At follow-up, three cases of recurrence occurred, but the uterine manipulator was not used. Conclusion: After five years of follow-up, recurrence rates in patients treated with minimally invasive surgery are about 10%, but the use of a uterine manipulator is not related to a higher level of recurrence rates. Full article

Electrochemotherapy (ECT) is one of the innovative strategies to overcome the multi drug resistance (MDR) that often occurs in cancer. Resistance to anticancer drugs results from a variety of factors, such as genetic or epigenetic changes, an up-regulated outflow of drugs, and various cellular and molecular mechanisms. This technology combines the administration of chemotherapy with the application of electrical pulses, with waveforms capable of increasing drug uptake in a non-toxic and well tolerated mechanical system. ECT is used as a first-line adjuvant therapy in veterinary oncology, where it improves the efficacy of many chemotherapeutic agents by increasing their uptake into cancer cells. The chemotherapeutic agents that have been enhanced by this technique are bleomycin, cisplatin, mitomycin C, and 5-fluorouracil. After their use, a better localized control of the neoplasm has been observed. In humans, the use of ECT was initially limited to local palliative therapy for cutaneous metastases of melanoma, but phase I/II studies are currently ongoing for several histotypes of cancer, with promising results. In this review, we described the preclinical and clinical use of ECT on drug-resistant solid tumors, such as head and neck squamous cell carcinoma, breast cancer, gynecological cancer and, finally, colorectal cancer. Full article

Introduction: Immune checkpoint inhibitors (ICIs) have become the standard of treatment for patients with non-small cell lung cancer (NSCLC). However, there are still many uncertainties regarding the selection of the patient who could benefit more from this treatment. This study aims to evaluate the prognostic and predictive role of clinical and biological variables in unselected patients with advanced NSCLC candidates to receive ICIs. Methods: This is an observational and prospective study. The primary objective is the evaluation of the relationship between clinical and biological variables and the response to ICIs. Secondary objectives included: safety; assessment of the relationship between clinical and biological parameters/concomitant treatments and progression-free survival at 6 months and overall survival at 6 and 12 months. Nomograms to predict these outcomes have been generated. Results: A total of 166 patients were included. An association with response was found in the presence of the high immunohistochemical PD-L1 expression, squamous cell histotype, and early line of treatment, whereas a higher probability of progression was seen in the presence of anemia, high LDH values and neutrophil/lymphocyte ratio (NLR), pleural involvement, and thrombosis before treatment. The nomogram showed that anemia, PD-L1 expression, NLR, and LDH represented the most informative predictor as regards the three parameters of interest. Conclusions: In the era of personalized medicine, the results are useful for stratifying the patients and tailoring the treatments, considering both the histological findings and the clinical features of the patients. Full article

Patients with non-small cell lung cancer, especially adenocarcinomas, harbour at least one oncogenic driver mutation that can potentially be a target for therapy. Treatments of these oncogene-addicted tumours, such as the use of tyrosine kinase inhibitors (TKIs) of mutated epidermal growth factor receptor, have dramatically improved the outcome of patients. However, some patients may acquire resistance to treatment early on after starting a targeted therapy. Transformations to other histotypes—small cell lung carcinoma, large cell neuroendocrine carcinoma, squamous cell carcinoma, and sarcomatoid carcinoma—have been increasingly recognised as important mechanisms of resistance and are increasingly becoming a topic of interest for all specialists involved in the diagnosis, management, and care of these patients. This article, after examining the most used TKI agents and their main biological activities, discusses histological and molecular transformations with an up-to-date review of all previous cases published in the field. Liquid biopsy and future research directions are also briefly discussed to offer the reader a complete and up-to-date overview of the topic. Full article

The most frequent form of colorectal cancer is represented by adenocarcinoma being about 98% of tumor histological types. However, other rare histotypes can be found in colon and rectum (adenosquamous, goblet cell adenocarcinoma, lymphoma, medullary carcinoma, melanoma, mesenchymal, neuroendocrine, plasmacytoma, signet ring, squamous tumors). Altogether, these forms account for less than 2% of colorectal tumors. There are no specific diagnostic or therapeutic recommended approaches and most of the information available from literature derives from small and retrospective clinical series. In the present study, we provide a paramount and updated view on clinical and biologic characteristics of rare colorectal tumors. Full article

Background. Although positron emission tomography/computed tomography, often integrated with 2-deoxy-2-[fluorine-18] fluorine-D-glucose (18F-FDG-PET/CT), is fundamental in the assessment of lung cancer, the relationship between metabolic avidity of different histotypes and maximum standardized uptake value (SUVmax) has not yet been thoroughly investigated. The aim of the study is to establish a reliable correlation between Suvmax and histology in non-small cell lung cancer (NSCLC), in order to facilitate patient management. Methods. We retrospectively assessed the data about lung cancer patients entered in the Italian Registry of VATS Group from January 2014 to October 2019, after establishing the eligibility criteria of the study. In total, 8139 patients undergoing VATS lobectomy were enrolled: 3260 females and 4879 males. The relationship between SUVmax and tumor size was also analyzed. Results. The mean values of SUVmax in the most frequent types of lung cancer were as follows: (a) 4.88 ± 3.82 for preinvasive adenocarcinoma; (b) 5.49 ± 4.10 for minimally invasive adenocarcinoma; (c) 5.87 ± 4.18 for invasive adenocarcinoma; and (d) 8.85 ± 6.70 for squamous cell carcinoma. Processing these data, we displayed a statistically difference (p < 0.000001) of FDG avidity between adenocarcinoma and squamous cell carcinoma. Moreover, by classifying patients into five groups based on tumor diameter and after evaluating the SUVmax value for each group, we noted a statistical correlation (p < 0.000001) between size and FDG uptake, also confirmed by the post hoc analysis. Conclusions. There is a correlation between SUVmax, histopathology outcomes and tumor size in NSCLC. Further clinical trials should be performed in order to confirm our data. Full article