Familial syndromes associated with testicular and paratesticular neoplasms: a comprehensive review.

A syndromic association between a subset of testicular/paratesticular neoplasms is well established. Such examples include Carney complex and large cell calcifying Sertoli cell tumor, Peutz-Jeghers syndrome and intratubular large cell hyalinizing Sertoli cell neoplasia, and VHL syndrome and clear cell papillary cystadenoma of the epididymis.However, recent studies proposed potential novel links between some testicular and paratesticular neoplasms with certain tumor syndromes. While more studies are still needed to solidify these associations, recent research suggests that a subset of Leydig cell tumors may arise in patients with hereditary leiomyomatosis and renal cell carcinoma syndrome or that some seminomas may occur in Lynch syndrome patients. Additionally, an association between testicular sex cord stromal tumors and paratesticular sarcomas with Familial adenomatous polyposis syndrome and DICER1 syndrome, respectively, has been proposed as well. This review provides a comprehensive overview of the intricate relationship between familial syndromes and associated testicular and paratesticular tumors, shedding light on their clinicopathological and molecular characteristics.

Dedifferentiated liposarcoma of the spermatic cord.

A man in his 60s presented to an outside hospital with persistent groin pain and a scrotal mass which was thought to be a recurrent hernia. Three months after initial presentation, the patient was found to have dedifferentiated liposarcoma (LPS) of the spermatic cord. LPS of the spermatic cord is a rare entity; however, clinicians should have LPS on the differential diagnosis especially in men with recurrent scrotal pain and mass. If unrecognised, LPS is associated with a high degree of morbidity and mortality. LPS can be subdivided into well-differentiated LPS, dedifferentiated LPS, myxoid LPS and pleomorphic LPS. In patients with advanced or metastatic LPS, chemotherapy consisting of Adriamycin, ifosfamide and mesna is used despite LPS being relatively chemoresistant. Therapies inhibiting mouse double minute 2 homologue, an oncoprotein that is a negative regulator of the tumour suppressor p53, appear to be promising in preclinical trials.

Large Malignant Testicular/Paratesticular Tumors in Adolescence: Assessment of Gross Tumor Size in a Vulnerable Age Group.

OBJECTIVE: We hypothesized that reticence to address a groin mass may result in late presentation of testicular/paratesticular malignancy in early puberty through adolescence. METHODS: Malignant testicular and paratesticular tumors (malignant germ cell tumors and rhabdomyosarcomas) diagnosed at our institution from 1994-2023 for patients aged 11-20 were included. Clinicopathologic features were recorded, and statistically analyzed. RESULTS: Eighty-five cases were identified. Patient ages ranged from 11 to 20 years (mean 17 years, median 16 years). The greatest tumor dimension ranged from 0.8 to 18.0 cm (mean 4.4 cm, median 3.5 cm). Ten tumors (11.8% of cases) were ≥10.0 cm. In the 11-13-year-old age group, 100% of tumors (3/3) were ≥10 cm. The proportion of tumors ≥10 cm was significantly higher in the 11-13-year-old age group than in either the 14-16-year-old (P<0.001) or 17-20-year-old (P<0.001) age groups. CONCLUSION: This adolescent cohort with malignant testicular and paratesticular tumors showed a high proportion (11.8%) of very large (≥10 cm) tumors. Although the reasons are unknown and likely multifactorial, this study suggests that adolescents, particularly the 11-13 year age group, are a vulnerable population.

Initial local resection versus early referral for spermatic cord sarcoma: Any impact on treatment timelines and oncological outcomes?

OBJECTIVES: Spermatic cord sarcomas are exceedingly rare, often misdiagnosed and subsequently improperly treated at local hospitals. This retrospective study looked at the oncological outcomes of spermatic cord sarcoma cases managed with curative intent resection at a tertiary referral sarcoma centre. We specifically studied how initial inadequate resections impact the oncologic outcomes compared to primary tumour resections at the reference centre. METHODS: One hundred eighteen consecutive patients affected by primary, localized spermatic cord sarcoma surgically managed at our reference centre from January 2001 through January 2021 were included. Primary endpoints were local relapse free (LRFS), distant metastasis free (DMFS) and overall survival (OS). These outcomes were evaluated with multi-nomial logistic regression and Cox proportional hazards regression models for a co-relation to known patient, tumour and treatment-related prognostic factors, including a prior inadequate resection and time from diagnosis to a complete oncologic resection as independent variables. Secondarily, we compared the above variables and treatment intervals among the subgroups of primary versus re-resection surgery. RESULTS: Over a median follow-up of 54 months (IQR 25-105), 12 patients (10.2%) developed local recurrence (LR) and 14 (11.6%) had distant metastasis (DM). 5-year local relapse (LRFS) and distant metastasis-free survival (DMFS) were 89.3% and 86.5%, respectively. Higher tumour grade and size were associated with a worse DMFS (p=<0.05). Likewise, marginal (R1) resection correlated with an inferior LRFS (p=< 0.05). Eighty-four patients (71.2%) had their initial diagnosis established on an inadequate surgical excision performed in a local hospital, followed by a re-excision at our centre (Re-resection group). During the same period, 34 (28.8%) were managed primarily with biopsy and treatment at our reference centre (Primary-resection group). The two groups had statistically significant differences in tumour size, histopathology, surgery duration, rate of postoperative complication and R0 resection (p < 0.005). Additionally, the difference in time intervals to achieve the treatment targets was statistically insignificant and did not correlate to the risk of recurrence as an independent variable. Residual disease was present in 51.2 % (n = 43) of the re-excision specimens. However, following a complete R0 resection, this did not correlate with a higher risk of recurrence (p = 0.481). CONCLUSION: Prompt referral to a tertiary centre, where multidisciplinary evaluation and sound oncologic resections are the standard of treatment, can align the OS and DFS of patients receiving incomplete surgery elsewhere to those treated primarily in referral centres. The primary determinant of prognosis remains surgical margin, tumour size and grade.

Transgastric drainage for subdiaphragmatic abscess secondary to perforation of the sigmoid colon after cytoreductive surgery for advanced ovarian cancer.

Drainage of subdiaphragmatic abscesses is difficult due to its anatomical location and it can result in adverse events, including organ damage and the spread of infection. In recent years, endoscopic ultrasonography (EUS) guided drainage for upper abdominal abscesses has become available. We report a case of successful infection control using this procedure for a subdiaphragmatic cyst secondary to perforation of the sigmoid colon after cytoreductive surgery for advanced ovarian cancer. A Japanese woman in her 60s underwent laparotomy for ovarian cancer, and then developed sigmoid colon perforation 6 days after surgery. The emergency reoperation was performed, and a cyst suspected to be an antibiotic-resistant fungal abscess appeared under the left diaphragm in the postoperative period. We adopted an EUS-guided route for diagnostic and therapeutic drainage method, which enabled shrinkage of the cyst and did not concur further adverse events. This procedure was effective as a minimally invasive drainage route for subdiaphragmatic cysts.

Tuberculous peritonitis diagnosed following laparoscopic examination for suspected advanced ovarian cancer.

Laparoscopy for intra-abdominal exploration and tissue sampling is useful in advanced ovarian cancers, in which it is presumed to be difficult to achieve complete tumour reduction in the initial surgery. This is a report of a case of suspected advanced ovarian cancer in a patient, who underwent laparoscopic screening and was later pathologically diagnosed with tuberculous peritonitis. A woman in her 50s visited her local doctor with constipation. Since imaging showed massive ascites she was referred for further evaluation. We initially suspected advanced ovarian cancer due to the presence of massive ascites and multiple peritoneal nodules. However, histopathological examination indicated that the nodules were tubercles, and the patient was subsequently diagnosed with tuberculous peritonitis. It is important to be aware that tuberculosis peritonitis can be misdiagnosed or mistaken for advanced ovarian cancer. Preoperative diagnosis of tuberculous peritonitis is often difficult. Tuberculous peritonitis should be considered if intraoperative findings show diffuse nodular disseminated lesions.

Extramammary Paget's Disease of the Scrotal and Penile: A Case Report and Review of the Literature.

INTRODUCTION: Extramammary Paget's disease of the scrotum and penis is a relatively rare cutaneous malignant tumor. At present, its pathogenesis, and clinical and pathological characteristics are not very clear. This is controversial regarding surgical margin width to decrease the high recurrence rate. This paper aimed to report the case and review the literature of extramammary Paget's disease of scrotum and penis. CASE PRESENTATION: We presented the case of a 74-year-old male patient with the patchy erythema and pruritus in the perineum who was admitted to our department. Biopsy of the large plaque revealed Paget disease. Under the condition of ensuring negative surgical margins by rapid frozen pathology, a wide local excision of the lesion, bilateral orchiectomy, and adnexectomy were performed on the patient. Pathology revealed that many scattered vacuolated Paget cells were observed in the epidermal layer, and the diagnosis was Paget's disease of the scrotum and penis. The 2 cm outside the skin lesion was used as the initial surgical margin, and free skin flap transplantation was used to repair the surgical wound. The patient recovered well and was discharged 1 week after surgery. CONCLUSION: Currently, histopathologic biopsy is the most important diagnostic method for EMPD. Once confirmed, for patients eligible for surgical intervention, wide local excision of the lesion and rapid intraoperative frozen pathological examination should be performed as soon as possible. The skin flap transplantation is the first choice for the repair of large-scale wound after surgery.

A Giant Scrotal Neurofibroma in a Child Masquerading as Filariasis: Uncommon Presentation of a Common Disease.

Neurofibroma of the scrotum is a very uncommon benign neoplasm, specifically when it affects teenagers and is not associated with neurofibromatosis type I. To the best of our knowledge, only a couple of cases of neurofibroma in children have been documented. Here, we report a case study of a 17-year-old boy who had a giant scrotal lump for ten years masquerading clinically as filariasis. A provisional diagnosis of benign nerve sheath neoplasm was made based on cytology findings. The lump was surgically removed from the patient, and a histopathological and immunohistochemistry examination established the diagnosis of neurofibroma. The combined clinical, preoperative cytological, histological, and immunohistochemistry findings were not presented in the literature in any of the formerly documented cases of scrotal neurofibroma. The current case expands the spectrum of differential diagnoses for scrotal tumours that clinicians have previously observed.

Mullerian Serous Cystadenoma Occurring in the Scrotum Post-Orchidopexy: A Rarely Reported Yet Distinctive Entity.

Serous cystadenoma is a rare lesion in the para-testicular tissue, with even rarer reports of this entity occurring in the scrotum post-orchidopexy. We present such an occurrence, adding support for its existence as a distinct entity.

Multiple Penile and Scrotal Schwannomas in an Adult Patient: A Case Report.

INTRODUCTION: Schwannomas originate from the peripheral nerve sheaths and are mainly detected in the head, neck, or extremities. They are rarely encountered in the penoscrotal region. CASE PRESENTATION: Herein, we present a case of a penoscrotal schwannoma diagnosed and successfully treated in our center. A 40-year-old patient with a history of resection of a dorsal penile schwannoma presented with multiple nodular lesions at the scrotum, penile shaft, and radix, which were first noticed 5 years before his current presentation. He complained about penile pain and dyspareunia. Magnetic resonance imaging was performed for preoperative diagnosis. All nodular lesions were resected while preserving the neurovascular structures. The histopathological examination revealed benign lesions. The patient's complaints were resolved, and there was no recurrence during the 1-year follow-up. CONCLUSION: The primary treatment is surgical excision. The patients need close follow-up regarding the risks of recurrence and malignant transformation.

Advances in nanotechnology-enabled drug delivery for combining PARP inhibitors and immunotherapy in advanced ovarian cancer.

Advanced ovarian cancer is a malignancy that spreads beyond the ovaries to the pelvis, abdomen, lungs, or lymph nodes. Effective treatment options are available to improve survival rates in patients with advanced ovarian cancer. These include radiation, surgery, chemotherapy, immunotherapy, and targeted therapy. Drug resistance, however, remains a significant challenge in pharmacotherapeutic interventions, leading to reduced efficacy and unfavorable patient outcomes. Combination therapy, which involves using multiple drugs with different mechanisms of action at their optimal dose, is a promising approach to circumvent this challenge and it involves using multiple drugs with different mechanisms of action at their optimal dose. In recent years, nanotechnology has emerged as a valuable alternative for enhancing drug delivery precision and minimize toxicity. Nanoparticles can deliver drugs to specific cancer cells, resulting in higher drug concentrations at the tumor site, and reducing overall drug toxicity. Nanotechnology-based drug delivery systems have the potential to improve the therapeutic effects of anti-cancer drugs, reduce drug resistance, and improve outcomes for patients with advanced ovarian cancer. This literature review aims to examine the current understanding of combining poly (ADP-ribose) polymerase (PARP) inhibitors and immunotherapy in treating advanced ovarian cancer and the potential impact of nanotechnology on drug delivery.

Testicular/paratesticular mesothelial tumours: Uncommon histopathologic entities in a very complex anatomical site.

Mesothelial tumours of the testicular/paratesticular region are uncommon, poorly characterised and difficult-to-diagnose lesions. They encompass entirely benign proliferations (adenomatoid tumour) and malignant, very aggressive tumours (mesothelioma) whose morphological features can be overlapping, highly variable and confounding. Moreover, testicular/paratesticular mesothelial tumours comprise relatively new entities with indolent behaviour (well-differentiated papillary mesothelial tumour) as well as tumours which cannot be correctly included in any of the aforementioned categories and whose classification is still controversial. The molecular profile of such tumours represents an open issue. In fact, despite the recent discoveries about the genomic landscape of mesothelial proliferations at other sites (pleura, peritoneum), testicular/paratesticular mesothelial tumours, and namely mesotheliomas, are too rare to be extensively studied on large case series and they could arguably hide relevant differences in their molecular background when compared to the more common pleural/peritoneal counterparts.The aim of this review is to provide a guide for the pathological assessment of testicular/paratesticular mesothelial tumours. Herein, we describe the most recent updates on this topic according to the latest (year 2022) World Health Organisation Classification of Urinary and Male Genital Tumours (5th edition) and current literature. The diagnostic criteria, the main differentials and the role of ancillary techniques in the diagnosis of mesothelial testicular/paratesticular tumours are discussed.

Paratesticular Dedifferentiated Liposarcoma with Rhabdomyoblastic Differentiation: A Case Report and Review of the Literature.

Liposarcomas of the paratesticular tissue is a rare pathological entity. The symptoms are similar to inguinal hernias or hydroceles. We present the case of an 84-year-old man with a rare paratesticular liposarcoma that manifested as painless right hemiscrotal swelling. Testicular tumour markers were negative. Imaging revealed a heterogeneous mass with a fat component. He underwent a radical orchiectomy on the left side to remove the associated mass. This revealed dedifferentiated liposarcoma (DDLS) with rhabdomyoblastic differentiation and MDM2 amplification. The surgical margins were negative, and the patient had a metastatic workup that included magnetic resonance imaging (MRI) of the abdomen and pelvis. Because of the disease's rarity, there is no clear agreement on radiotherapy and chemotherapy roles.

Digital ischaemia as a presenting feature in metastatic ovarian cancer.

A woman in her 50s presented with acute pain and discolouration in the fingertips of both hands, without other features of connective tissue disease. The history was otherwise significant for abdominal bloating, altered bowel habit, urinary urgency and fatigue. Inflammatory markers, antinuclear antibodies, serum protein electrophoresis and complement levels were all normal. The tumour marker CA125 was significantly elevated, prompting a CT abdomen and pelvis, which revealed a large right-sided adnexal mass with multiple enhancing peritoneal and omental nodules and moderate ascites, suggestive of disseminated primary ovarian cancer.Digital ischaemia (DI) can be associated with cancer in up to 15% of cases. An underlying cancer should be suspected in patients presenting with new or worsening symptoms of DI. Prompt treatment with anticancer therapies can achieve complete resolution of DI.

Liposarcoma of spermatic cord mimicking an inguinal hernia A case report and review of the literature.

AIM: Liposarcoma of the spermatic cord (LSC) is a tumour often mistaken for common inguinal swelling as hernia and the aim of this work is to present our case with a review of the Literature to define the management of this rare condition. MATERIAL OF STUDY: A systematic review has been realised, considering English language articles published on Pubmed, between 1956 and 2022, using as key words "Liposarcoma of the spermatic cord". RESULTS: 160 studies described 420 cases of LSC and in 40 cases the patient had undergone surgery with an initial diagnosis of inguinal hernia. DISCUSSION: LSC is a very rare entity of genitourinary malignancies, occurring more often in the spermatic cord and diagnosis can be difficult. Our case and Literature data confirm the role of imaging in not conventional inguinal swelling, to avoid diagnostic mistakes and to define preoperatively the correct surgical management. CONCLUSIONS: Imaging is mandatory in case of diagnostic doubt. The recommended treatment is a radical high orchiectomy with clear margins. A long follow-up period is necessary to detect a local recurrence which may occur even several years after the primary therapy. KEY WORDS: Inguinal swelling, Liposarcoma, Spermatic cord.

Primary squamous cell carcinoma of the scrotum: Outcomes from a specialist center.

BACKGROUND: Squamous cell carcinoma (SCC) of the scrotum is a rare and aggressive cancer. There are no established guidelines on the management of scrotal SCC. OBJECTIVE: To analyze the clinical management and outcomes of scrotal SCC. PATIENTS AND METHODS: A retrospective analysis of patients diagnosed with primary scrotal SCC over a 10-year period was performed. The type of surgery, tumor stage and histological subtypes, recurrence rate and metastases, cancer-specific mortality (CSM), and other-cause mortality (OCM) were analyzed. RESULTS: Between 2012 and 2022, a total of 10 men were identified with primary scrotal SCC. The median (interquartile, IQR) age was 65.5 (55-77) years. Wide local excision was performed in 9 patients and 1 patient underwent a total scrotectomy. The pathological T-stage was: pT1, n = 3; pT2, n = 1; pT3, n = 5 (50%); pT4, n = 1. Four patients had pathologically positive inguinal lymph nodes and 2 had distant metastatic disease at presentation. At a median (IQR) follow-up of 10.5 (4-31) months 5 patients died, of which 3 died from scrotal SCC. CONCLUSION: Scrotal SCC is extremely rare in the UK with only 10 primary cases identified in our center over the past 10 years. Surgical resection of the tumor and appropriate inguinal node staging are required due to a high proportion of cases which metastasize to the inguinal lymph nodes. PATIENT SUMMARY: Scrotal cancer is rare. 10 cases were diagnosed over 10 years at a single center. Around half had disease spread to the groin nodes or distant organs at presentation. Surgical resection was required in all patients. At the time of analysis, half of the patients are alive. Due to the rarity and aggressiveness of the cancer, management should be carried out within a specialist center.

Neo-adjuvant chemotherapy does not reduce surgical complexity nor the accuracy of intra-operative visual assessment of disease in advanced ovarian cancer.

AIM: Compare the surgical complexity and histological accuracy of visual inspection of disease in patients undergoing primary debulking (PDS) versus delayed debulking surgery (DDS) following neo-adjuvant chemotherapy (NACT) for advanced ovarian cancer (AOC). MATERIALS AND METHODS: All patients undergoing PDS or DDS for stage III / IV AOC at a UK cancer centre between January 2014-October 2021 were included. Retrospective data was collected accessing an electronic gynaecological oncology database, operation and histology records. Comparative frequencies of surgical procedures performed were calculated for primary versus delayed cohorts; and correlation between intra-operative suspicion of disease and specimen histology at PDS and DDS compared. RESULTS: N=232. PDS was performed in 45.3% and DDS in 54.7% of patients; achieving complete cytoreduction in 77.2%. Appendicectomy, pelvic and para-aortic nodal dissection were undertaken significantly more often at primary surgery; whilst right diaphragm stripping, pelvic peritonectomy, splenectomy and cholecystectomy were more likely following NACT. We found no variation in bowel resection rates between cohorts. For the majority of specimens, there was no difference in correlation between intra-operative suspicion of disease and final histopathology - with a significantly lower positive predictive value for visual assessment demonstrated only for liver capsule and pelvic peritoneum at DDS. CONCLUSION: NACT does not appear to reduce the complexity of surgery, including rates of bowel resection; nor accuracy of intra-operative visual assessment of disease. We therefore caution against both deferring to NACT to facilitate less radical delayed debulking; and any presumption that macroscopically abnormal tissue at DDS may represent inert post-NACT 'burn-out', mitigating indication for excision. We instead suggest reservation of the neo-adjuvant pathway for patients with poor PS and radiologically-confirmed surgical stopping points; and advocate equivalent and maximal cytoreductive effort to remove all visibly abnormal tissue in both the upfront and delayed surgical settings.