Quantitative ADC: An Additional Tool in the Evaluation of Prostate Cancer?

Prostate cancer is one of the most common tumors among the male population. Magnetic resonance imaging (MRI), standardized by the PI-RADS version 2.1 scoring system, has a fundamental role in detecting prostate cancer and evaluating its aggressiveness. Diffusion-weighted imaging sequences and apparent diffusion coefficient values, in particular, are considered fundamental for the detection and characterization of lesions. In 2016 the International Society of Urological Pathology introduced a new anatomopathological 5-grade scoring system for prostate cancer. The aim of this study is to evaluate the correlation between quantitative apparent diffusion coefficient values (ADC) derived from diffusion-weighted imaging (DWI) sequences and the International Society of Urological Pathology (ISUP) and PI-RADS groups. Our retrospective study included 143 patients with 154 suspicious lesions, observed on prostate magnetic resonance imaging and compared with the histological results of the biopsy. We observed that ADC values can aid in discriminating between not clinically significant (ISUP 1) and clinically significant (ISUP 2-5) prostate cancers. In fact, ADC values were lower in ISUP 5 lesions than in negative lesions. We also found a correlation between ADC values and PI-RADS groups; we noted lower ADC values in the PI-RADS 5 and PI-RADS 4 groups than in the PI-RADS 3 group. In conclusion, quantitative apparent diffusion coefficient values can be useful to assess the aggressiveness of prostate cancer.

Angiomatoid Fibrous Histiocytoma (AFH) of the Right Arm: An Exceptional Case with Pulmonary Metastasis and Confirmatory EWSR1::CREB1 Translocation.

Angiomatoid fibrous histiocytoma (AFH) is a rare neoplasm described for the first time by Enzinger in 1979, and classified by World Health Organization 2020 as intermediate malignant potential neoplasm. It mostly occurs in the subcutis and is characterized by varying proportions of epithelioid, ovoid and spindle cells in a nodular and syncytial growth pattern, with some hemorrhagic pseudovascular spaces. In this paper, we report the clinical case of a 62-year-old man who presented with AFH on the right arm, and relapsed three years after first surgical excision. After a further three years, the patient presented with an intramuscular localization of AFH, and 12 months after this, a pulmonary metastasis of AFH was diagnosed. Given the rarity of the spreading of AFH, we performed Fluorescence In Situ Hybridization (FISH) and we detected EWSR1::CREB1 gene fusion.

Automated Analysis of Proliferating Cells Spatial Organisation Predicts Prognosis in Lung Neuroendocrine Neoplasms.

Lung neuroendocrine neoplasms (lung NENs) are categorised by morphology, defining a classification sometimes unable to reflect ultimate clinical outcome. Subjectivity and poor reproducibility characterise diagnosis and prognosis assessment of all NENs. Here, we propose a machine learning framework for tumour prognosis assessment based on a quantitative, automated and repeatable evaluation of the spatial distribution of cells immunohistochemically positive for the proliferation marker Ki-67, performed on the entire extent of high-resolution whole slide images. Combining features from the fields of graph theory, fractality analysis, stochastic geometry and information theory, we describe the topology of replicating cells and predict prognosis in a histology-independent way. We demonstrate how our approach outperforms the well-recognised prognostic role of Ki-67 Labelling Index on a multi-centre dataset comprising the most controversial lung NENs. Moreover, we show that our system identifies arrangement patterns in the cells positive for Ki-67 that appear independently of tumour subtyping. Strikingly, the subset of these features whose presence is also independent of the value of the Labelling Index and the density of Ki-67-positive cells prove to be especially relevant in discerning prognostic classes. These findings disclose a possible path for the future of grading and classification of NENs.

Urological Melanoma: A Comprehensive Review of a Rare Subclass of Mucosal Melanoma with Emphasis on Differential Diagnosis and Therapeutic Approaches.

Melanoma is reported as the 19th most common cancer worldwide, with estimated age-standardized incidence rates of 2.8-3.1 per 100,000. Although the origin is most frequently cutaneous, mucosal melanoma has been described several times in literature, and despite its rarity (only 1% of all melanomas), increasing attention is being paid to this disease form. Within this subgroup, melanomas of the uropoetic apparatus are a rarity among rarities. Indeed, less than 50 cases of primary melanoma originating from the urinary bladder have been described, and even less originating from the kidney, renal pelvis and urethra. In this work, we present a detailed review of the literature related to this subclass of mucosal melanoma, delve into the biological landscape of this neoplasm and discuss current approaches, future perspectives and potential therapeutic approaches.

Pulmonary Sclerosing Pneumocytoma: A Pre and Intraoperative Diagnostic Challenge. Report of Two Cases and Review of the Literature.

Pulmonary sclerosing pneumocytoma is a rare benign pulmonary tumor of primitive epithelial origin. Because of the unspecific radiological features mimicking malignancies and its histological heterogeneity, the differential diagnosis with adenocarcinoma and carcinoid tumors is still challenging. We report our experience of two cases of sclerosing pneumocytoma, as well as a review of the literature. Immunohistochemical findings showed intense staining of the cuboidal epithelial cells for cytokeratin-pool and TTF-1, with focal positivity for progesterone receptors. Round and spindle cells expressed positivity for vimentin, TTF-1 and focally for the progesterone receptor. Cytologic diagnosis of pulmonary pneumocytoma requires the identification of its dual cell population, made up of abundant stromal cells and fewer surface cells. Since the pre- and intraoperative diagnosis should guide surgical decision making, obtaining a sufficient specimen size to find representative material in the cell block is of paramount importance.

Rare gastrointestinal metastases from primary lung cancer. Two case reports of patients managed with emergency surgery.

BACKGROUND: Lung cancer represents the second leading cause of death in US and the high mortality rate could be related to the diagnosis, usually, performed in an advanced metastatic stage. Gastrointestinal metastases from non-small cell lung cancer, are extremely rare and only few cases complicated by digestive haemorrhage and/or perforation have been reported in literature. MATERIAL AND METHODS: We report two cases of gastrointestinal metastases and their rare clinical onset with haemorrhage and perforation of the digestive tract. Both patients were admitted in an emergency setting. The first case was a 59-year-old man complained of abdominal pain and massive gastrointestinal haemorrhage. An upper gastrointestinal endoscopy revealed an ulcerated gastric mass and an emergency CT-scans showed a right lung mass with biopsy conclusive for a large cell lung cancer. The second case was a 62-year-old man with abdominal pain and shock due to gastrointestinal bleeding. He was submitted to an emergency CT-scan showing two lung nodules (1.0 and 3.5 cm of diameter) as well as widespread metastases, intraperitoneal free air and fluids. RESULTS: Both patients were surgical managed in emergency and pathology revealed the metastatic origin from an unknown large-cell lung cancer and a rare lung adenocarcinoma in the second one. CONCLUSIONS: Despite the rare clinical condition, in patients with a diagnosis of lung cancer managed in emergency for gastrointestinal complication, gastrointestinal metastases should be taken into account, and referred to the primary disease in order to tailor the best approach. KEY WORDS: Gastrointestinal metastases, Lung cancer, Tailored surgery.

Loss of STK11 expression is an early event in prostate carcinogenesis and predicts therapeutic response to targeted therapy against MAPK/p38.

Prostate cancer (PCa) is the second leading cause of cancer-related death in men; however, the molecular mechanisms leading to its development and progression are not yet fully elucidated. Of note, it has been recently shown that conditional stk11 knockout mice develop atypical hyperplasia and prostate intraepithelial neoplasia (PIN). We recently reported an inverse correlation between the activity of the STK11/AMPK pathway and the MAPK/p38 cascade in HIF1A-dependent malignancies. Furthermore, MAPK/p38 overactivation was detected in benign prostate hyperplasia, PIN and PCa in mice and humans. Here we report that STK11 expression is significantly decreased in PCa compared to normal tissues. Moreover, STK11 protein levels decreased throughout prostate carcinogenesis. To gain insight into the role of STK11-MAPK/p38 activity balance in PCa, we treated PCa cell lines and primary biopsies with a well-established MAPK14-MAPK11 inhibitor (SB202190), which has been extensively used in vitro and in vivo. Our results indicate that inhibition of MAPK/p38 significantly affects PCa cell survival in an STK11-dependent manner. Indeed, we found that pharmacologic inactivation of MAPK/p38 does not affect viability of STK11-proficient PCa cells due to the triggering of the AMPK-dependent autophagic pathway, while it induces apoptosis in STK11-deficient cells irrespective of androgen receptor (AR) status. Of note, AMPK inactivation or autophagy inhibition in STK11-proficient cells sensitize SB202190-treated PCa cells to apoptosis. On the other end, reconstitution of functional STK11 in STK11-deficient PCa cells abrogates apoptosis. Collectively, our data show that STK11 is a key factor involved in the early phases of prostate carcinogenesis, and suggest that it might be used as a predictive marker of therapeutic response to MAPK/p38 inhibitors in PCa patients.

Spondin-2, a secreted extracellular matrix protein, is a novel diagnostic biomarker for prostate cancer.

PURPOSE: SPON2 belongs to the F-spondin family of secreted extracellular matrix proteins. It is deregulated in some tumors, including prostate cancer. In this prospective study we assessed the role of serum SPON2 as a biomarker for prostate cancer diagnosis as well as any association between SPON2 levels and clinicopathological features. We also compared the diagnostic performance of this biomarker to that of serum sarcosine, and percent free-to-total and total prostate specific antigen. MATERIALS AND METHODS: SPON2 was measured using a sandwich enzyme linked immunosorbent assay in serum samples from 286 patients with prostate cancer and 68 with no evidence of malignancy, as confirmed by 10 to 12-core ultrasound guided prostate biopsy. Nonparametric statistical tests and ROC analysis were done to assess the diagnostic performance of SPON2 vs the other biomarkers. RESULTS: Median serum SPON2 was significantly higher in patients with prostate cancer than in those with no evidence of malignancy (77.5 vs 23.6 ng/ml, p<0.0001). ROC analysis showed a higher predictive value of SPON2 (AUC 0.952) than of serum sarcosine (AUC 0.674), percent free-to-total prostate specific antigen (AUC 0.806) and total prostate specific antigen (AUC 0.561). Moreover, patients with low grade prostate cancer had higher median SPON2 levels (p=0.001). Spearman rank correlation confirmed a negative association with Gleason score (rs=-0.29, p=0.0005). CONCLUSIONS: We found evidence that SPON2 levels were significantly higher in patients with prostate cancer than in healthy individuals. Moreover, this biomarker had better diagnostic performance than serum sarcosine, and percent free-to-total and total prostate specific antigen. This greater accuracy was also present in a subset of patients with normal prostate specific antigen.

Testicular granulosa cell tumor of adult type: a new case and a review of the literature.

Testicular granulosa cell tumor of the adult type is a very rare tumor, and, to date and our knowledge, only 23 cases of this rare testicular tumor have been reported in the literature, 5 of which developed metastases. We report a case of granulosa cell tumor of adult type in a 45-year-old man with a 15-year history of a painless increasing right testicular volume who underwent radical orchiectomy. The patient is disease-free after a 2-year follow-up, without any adjuvant therapy. Our case and a review of the literature indicate that this type of tumor is a rare, slow-growing neoplasm. Because distant metastases may occur late in the clinical course, long-term follow-up of these patients is recommended.

A case of cryptogenic organizing pneumonia occurring in Crohn's disease.

A 29 year-old-man with Crohn's disease, who developed diffuse pulmonary infiltrates and hypoxemia two months following oral administration of mesalazine, was examined. Clinical findings and computed tomography were suggestive of, and lung histology was diagnostic of, bronchiolitis obliterans organizing pneumonia, also known as cryptogenic organizing pneumonia. Although the data did not allow for definitive conclusions, they did suggest that the pulmonary disease was an extraintestinal manifestation of Crohn's disease, rather than an adverse reaction to mesalazine. In fact, the patient showed clinical, radiological and functional improvements, despite the treatment with mesalazine and the withdrawal of steroid therapy.

Ileal intussusception due to intestinal metastases from primary malignant melanoma of the lung.

Primary malignant melanoma of the lung (PMML) is an uncommon tumor with very few cases reported in the literature that satisfy the required criteria to establish a primary bronchial origin. We report a case of a 44-year-old man with acute abdominal distress and a right pulmonary roentgenographic opacity. A cranial-thoracic-abdominal CT scan confirmed the presence of a pulmonary nodule with bilateral cerebral metastases and marked dilatation of intestinal loops. At laparotomy an ileal intussusception was noted and an ileal resection was done. The resected intestinal segment contained three endoluminal polypoidal formations. Histological and immunohistochemical analyses showed the presence of multiple sites of melanoma. These lesions as well as the brain lesions clearly appeared metastatic. The patient underwent further evaluation to identify a primary site of melanoma; bronchoscopy was performed with biopsy of the pulmonary nodule. Pathology revealed a neoplastic process of fusiform cells, with focal presence of melanic inter- and extracellular pigment. The immunohistochemical analysis confirmed the diagnosis of PMML. We discuss the criteria for diagnosis and histogenesis of PMML along with this unusual presentation.