Tumour Budding Is an Independent Predictive Factor of Cutaneous Squamous-cell Carcinoma Aggressiveness.

BACKGROUND/AIM: Tumour budding (TB), i.e. the presence of groups of ≤5 tumour cells ahead of the invasive tumour front, is a pathological feature associated with an aggressive outcome in several cancer types. The aim of this study was to assess the value of TB as an independent prognostic factor of cutaneous squamous cell carcinomas (cSCC). MATERIALS AND METHODS: We studied 25 cases of aggressive cSCC (defined as tumours that developed local recurrences and/or metastases after adequate excision) and 27 cases of non-aggressive cSCC. TB was expressed as the mean number of tumour buds in 5 adjacent high-power fields (HPF). RESULTS: Statistical analysis showed that TB is an independent predictive factor of cSCC aggressiveness. When the cut-off value of 0.8 buds/HPF was considered, the positive and negative predictive values for cSCC aggressiveness reached 77.3% and 75.0%, respectively. CONCLUSION: As with other cancer types, TB appears to be a new independent pathological factor of aggressiveness of cSCC, providing a new tool to predict cSCC outcome, similar to other already established features associated with an adverse outcome (such as tumour size).

Treatment of a Gastrointestinal Stromal Tumor (GIST) Adherent to the Spleen and the Tail of the Pancreas: A Case Report.

BACKGROUND Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal gastrointestinal tumors (GIT). Usually, they appear in patients ages 55-65 years, with no apparent difference between males and females. Their annual incidence is about 11-14 per 106. They generally do not present with any prominent symptoms, appearing with the atypical symptoms of abdominal pain, weight loss, early satiety, and occasionally bleeding. Adequate surgical treatment involves sphenoid resection of the tumor within clear margins. If adjacent organs are involved, en bloc resection is the procedure of choice. CASE REPORT A 62-year-old male patient presented to the Emergency Department complaining of melena for 1 week. He underwent gastroscopy, colonoscopy and abdominal computed tomography scan, which revealed a large, exophytic, lobular mass (12.6×9.7×12 cm) of the greater curvature of the stomach. The patient underwent en bloc sphenoid gastrectomy, splenectomy, and caudal pancreatectomy. The histopathologic examination revealed findings compatible with a gastrointestinal stromal tumor located at the stomach, with low-grade malignancy (G1) and T4N0 according to TNM classification. He was discharged from the hospital on the 7th postoperative day. CONCLUSIONS GISTs are uncommon tumors of the gastrointestinal system that usually do not invade neighboring organs or develop distant metastases; therefore, local resection is usually the treatment of choice. However, in cases of large GISTs that are adherent to neighboring organs, en bloc resection and resection of adjacent organs may be inevitable.

Prognostic implications of mismatch repair deficiency in patients with nonmetastatic colorectal and endometrial cancer.

BACKGROUND: The clinical relevance of mismatch repair (MMR) status in patients with nonmetastatic cancer across tumour types remains unclear. Our goal was to investigate the prognostic role of MMR deficiency in patients with stage I-III colorectal and endometrial cancer. METHODS: Patients with nonmetastatic colorectal and endometrial cancer with tumour tissue available for analysis were identified through the Hellenic Cooperative Oncology Group (HeCOG)'s tumour repository. Patients had been referred to Departments of Medical Oncology affiliated with HeCOG. MMR protein expression was evaluated by immunohistochemistry. The primary outcome measure was overall survival (OS). RESULTS: From May 1990 to September 2012, 1158 patients with nonmetastatic colorectal (N = 991) and endometrial cancer (N = 167) were identified (median age: 64 years, men: 544). All patients with colorectal and 109 (65%) with endometrial cancer had received adjuvant treatment. MMR deficiency was observed in 114 (11.5%) of colorectal and 80 (47.9%) of endometrial tumours. More commonly deficient proteins were PMS2 (69 patients, 7%) and MLH1 (63 patients, 6.5%) in colorectal cancer and MSH2 (58 patients, 34.7%) in endometrial cancer. Colorectal MMR-deficient (dMMR) tumours were more likely to be right sided (65 % dMMR vs 27 % proficient MMR, pMMR; p < 0.001), high grade (31% vs 15%, χ2, p < 0.001) and with a mucinous component (64% vs 42%, p < 0.001). Endometrial dMMR tumours were more often of endometrioid histology (51.4 % endometrioid vs 20 % serous/clear cell, p = 0.020). Compared with MMR proficiency, MMR deficiency was associated with improved OS in patients with endometrial cancer (HR = 0.38, 95% CI 0.20 to 0.76, p = 0.006), but not in patients with colorectal cancer (HR = 0.73, 95% CI 0.49 to 1.09, p = 0.130). After adjusting for age, stage and grade, MMR deficiency maintained its favourable prognostic significance in patients with endometrial cancer (HR = 0.42, 95% CI 0.20 to 0.88, p = 0.021). CONCLUSIONS: DMMR was associated with improved outcomes in patients with nonmetastatic endometrial cancer, but not in patients with nonmetastatic colorectal cancer who received adjuvant chemotherapy.

Management of low rectal gastrointestinal stromal tumor with neoadjuvant therapy and transanal excision: a rare case report and review of the literature.

BACKGROUND: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. However, rectal GISTs represent only 5% of this category. We report a case of a rectal GIST treated with local excision after neoadjuvant therapy. CASE PRESENTATION: A 41-year-old male patient presented with anal bleeding. Colonoscopy revealed a mass located 5 cm from the anal verge. Histological examination showed a GIST with immunohistochemical positivity for CD117 and CD34. Transanal local excision was performed after neoadjuvant therapy. CONCLUSION: Neoadjuvant immunotherapy for GISTs with unfavorable localization may facilitate local excision and avoid complications of more demanding operations.

Acute Interstitial Nephritis in a Patient with Non-Small Cell Lung Cancer under Immunotherapy with Nivolumab.

Immune-checkpoint-inhibitors (ICPIs) represent a novel class of immunotherapy against several malignancies. These agents are associated with several "immune-mediated" adverse effects, but the reported renal toxicity of ICPIs is less well defined. We present the case of a 60-year-old man with a history of non-small cell lung cancer, who developed acute kidney injury (AKI) approximately 3.5 months after initiation of immunotherapy with nivolumab. Urinalysis revealed sterile pyuria, without microscopic hematuria or proteinuria. Immunological examination was negative. A renal biopsy showed severe interstitial inflammatory infiltration of T-cells, monocytes, and eosinophils without interstitial granulomas and normal appearance of glomeruli, indicating acute interstitial nephritis (AIN) as the cause of AKI. After a short-term course of corticosteroids and permanent nivolumab discontinuation, partial recovery of renal function was noted. AIN is a rare adverse effect of ICPIs that mandates the close monitoring of renal function in patients under immunotherapy with these agents.

Mismatch repair deficiency and aberrations in the Notch and Hedgehog pathways are of prognostic value in patients with endometrial cancer.

The aim of this study was to investigate the prognostic value of the Hedgehog (Gli, Patched-1, Shh, Smo) and Notch (Jag1, Notch2, Notch3) pathway members, in comparison to a panel of proteins (ER, PgR, HER2/neu, Ki67, p53, p16, PTEN and MMR) previously suggested to be involved in the pathogenesis of endometrial cancer, in association with clinical outcome and standard clinicopathological characteristics. A total of 204 patients with histological diagnosis of endometrial cancer treated from 2004 to 2013 were included. The evaluation of protein expression was assessed by immunohistochemistry. Univariate analysis showed that higher Ki67 labeling, expression of PTEN, p16, Notch2 and Notch3 proteins, as well as MMR proficiency were associated with increased relapse and mortality rate. Additionally, Patched-1 protein expression was associated with worse DFS, while p53 overexpression was associated with worse OS. In multivariate analyses, patients with MMR proficient tumors had more than double risk for death than patients with MMR deficient (MMRd) tumors (adjusted HR = 2.19, 95% CI 1.05-4.58, p = 0.036). Jag1 positivity conferred reduced mortality risk (HR = 0.48, 95% CI 0.23-0.97, p = 0.042). However, as shown by hierarchical clustering, patients fared better when their tumors expressed high Jag1 protein in the absence of Notch2 and Notch3, while they fared worse when all three proteins were highly expressed. Patched-1 positivity conferred higher risk for relapse (HR = 2.04, 95% CI 1.05-3.96, p = 0.036). Aberrant expression of key components of the Notch and Hedgehog signaling pathways, as well as MMRd may serve as independent prognostic factors for recurrence and survival in patients with endometrial cancer.

Ideal treatment strategy for chylous mesenteric cyst: a case report.

BACKGROUND: A mesenteric chylous cyst is defined as a cyst occurring in the mesentery of the gastrointestinal tract anywhere from the duodenum to the rectum and is diagnosed most often during the fifth decade of life. CASE PRESENTATION: In our case report, we describe a case of 38-year-old Greek woman who presented at our Emergency Department complaining of abdominal pain without any other symptoms. Her medical and family histories were clear and she had never had any abdominal interventions. During an imaging examination with ultrasound of her abdomen, an anechoic lesion in her upper left abdomen was revealed. In a further investigation with computed tomography, a well-defined hypodense cystic 7.08 × 6.05 cm mass with mild enhancement was noted. The mass was excised by open laparotomy within healthy borders and the specimen was sent for pathological examination. The histopathological findings were found to be most consistent with a simple lymphatic (chylous) cyst of the mesentery. A review of the literature considering this rare entity was also performed to evaluate our treatment strategy and the result was analyzed. CONCLUSIONS: Chylous cysts represent a diagnostic challenge and they should be considered when a physician encounters an intraabdominal mass. Physical examination and imaging do not always provide a diagnosis and surgical management should be advised due to the potential complications that may develop.

mTOR Signalling Pathway-protein Expression in Post-transplant Cutaneous Squamous-cell Carcinomas Before and After Conversion to mTOR-inhibitors.

BACKGROUND/AIM: Inhibitors of the mammalian target of rapamycin (mTORis) exert immunosuppressive and antitumor effects and are used in organ-transplant recipients (OTR) as immunosuppressants able to reduce skin tumor burden. This study investigated the effects of mTORis on the expression of mTOR pathway proteins in cutaneous squamous-cell carcinomas (SCC) developing in OTR, before and after switching to mTORis. MATERIALS AND METHODS: An immunohistochemical study was performed on 23 SCC sections excised from OTR with post-transplant SCC, before or after switch to mTORis, with antibodies against pAkt, pmTOR and PI3K. RESULTS: pmTOR expression was found in 8/12 SCC pre-switch, and in 8/11 SCC post-switch, to mTORis. All (but 2) SCC expressed PI3K, and all SCCs expressed pAkt. CONCLUSION: mTORis do not significantly change the immunohistochemical expression of molecules upstream of the mTOR inhibition (pmTOR, PI3K, pAkt), in cutaneous SCC.

Corrigendum to "Surgical Management of a Giant Adrenal Pseudocyst: A Case Report and Review of the Literature in the Last Decade".

[This corrects the article DOI: 10.1155/2018/8473231.].

Surgical Management of a Giant Adrenal Pseudocyst: A Case Report and Review of the Literature in the Last Decade.

Adrenal pseudocysts are rare entities and occurred in the 5th and the 6th decades of life. They are discovered accidentally, while appearing with nonspecific clinical and imaging findings. We report a case of a 28-year-old woman presented in our Emergency Department complaining about upper abdomen pain. Computed tomography revealed a hypodense cystic lesion containing hyperdense material. The size of a mass was 11. 7 × 9.3 × 6.6 cm in diameter close to the pancreas, but the origin was from the left adrenal gland. The mass was excised with surgical laparotomy. Giant adrenal pseudocysts are rare entities. Final diagnosis usually confirmed with the pathology examination. Management of such adrenal lesions depends on the unique characteristics, the surgeon's experience, and local resources.

Double unilateral functioning adrenocortical adenomas.

Double functioning adrenocortical adenomas, occurring in the same gland is an extremely rare condition. This paper presents two cases of double functioning adrenocortical adenomas within the same adrenal gland, causing primary aldosteronism. Diagnosis was set histopathologically in one case since magnetic resonance imaging (MRI) failed to distinguish the two entities. In each case, a laparoscopic adrenalectomy was conducted. When preoperative imaging studies fail to report the presence of double adrenocortical adenomas, histopathology reports should be comprehensive enough so as to reveal such rare lesions.

Association of osteopontin with specific prognostic factors and survival in adjuvant breast cancer trials of the Hellenic Cooperative Oncology Group.

BACKGROUND: The shift towards an earlier diagnosis of breast cancer (BC) highlights the need for biomarkers that would identify patients at risk for relapse and metastatic spread and indicate the potential value of additional treatment strategies. Osteopontin (OPN) is a matricellular protein that has been suggested to be a potential biomarker in BC. In the present study, we used archived BC patient samples to assess the clinical utility of OPN. METHODS: Formalin-fixed paraffin-embedded tumor tissue samples from 975 patients were collected from two large phase III randomized adjuvant chemotherapy trials (HE10/97 and HE10/00) that included patients with high risk BC. All tissue samples were assessed for ER, PgR, Ki67 and HER2 protein expression. OPN protein and mRNA expression was evaluated using immunohistochemistry and quantitative reverse transcription-polymerase chain reaction, respectively. RESULTS: OPN mRNA expression data were available for 814 patients, whereas OPN protein expression data were available for 546 patients. The majority of patients were ER/PgR-positive (78.3%), HER2-negative (76.5%) and Ki67-positive (55.2%) and had received adjuvant radiation therapy (76.8%) and hormonal therapy (81.1%). OPN mRNA expression was significantly associated with age (60.9% in high OPN tumors vs. 54.1% in low OPN tumors, p = 0.047), ER/PgR-negative status (25.7 vs. 17.2%, p = 0.004) and BC subtypes (p = 0.021). In addition, high OPN mRNA expression was significantly associated with reduced DFS (HR 1.26, 95% CI 1.00-1.59, Wald's p = 0.050) and OS (HR 1.37, 95% CI 1.05-1.78, p = 0.019), while it retained its prognostic significance for both DFS (HR 1.39, 95% CI 1.10-1.77, p = 0.007) and OS (HR 1.54, 95% CI 1.61-2.05, p = 0.003) in the multivariate analysis. CONCLUSIONS: We showed that high OPN mRNA expression is associated with decreased DFS and OS in a large cohort of BC patients treated with adjuvant chemotherapy in a clinical trial setting. Our results suggest that OPN may serve as a prognostic factor and a potential target for therapy. Trial registration Australian New Zealand Clinical Trials Registry; HE10/97 ACTRN12611000506998; HE10/00 ACTRN12609001036202.

Tumour Budding Correlates with Aggressiveness of Cutaneous Squamous-cell Carcinoma.

BACKGROUND/AIM: Tumour budding (TB) is a specific pathological feature that has been found to be associated with an aggressive outcome in several cancer types; however, to our knowledge, TB has not yet been assessed in squamous-cell carcinomas of the skin (SCC). The aim of the study was to study whether TB correlates with aggressiveness in cutaneous SCC. MATERIALS AND METHODS: We examined 31 aggressive SCC (that later developed local recurrences or metastases) in comparison with 21 non-aggressive SCC (not complicated by recurrence or metastasis). TB was expressed as the mean number of tumour buds in five adjacent high-power fields of each SCC. RESULTS: Aggressive SCC had a much higher TB score compared to control SCC (1.63±1.35 vs. 0.49±0.9, p<0.001). CONCLUSION: As with other cancer types, TB seems to be a pathological marker of aggressiveness of cutaneous SCC, along with other features known to be associated with an aggressive outcome (tumour thickness, level of invasion and lymphovascular or perineural invasion). Further studies including a larger number of tumours will hopefully validate TB as a new pathological predictor of aggressiveness in cutaneous SCC and will allow its correlation with other pathological features of SCC aggressiveness to be defined.

Solitary fibrous tumor of the pancreas: Case report and review of the literature.

Solitary fibrous tumor (SFT) is a mesenchymal tumor typically located in the pleura, but can also be found as an asymptomatic mass in other areas, including the liver, peritoneum, kidney and salivary glands. However, SFT rarely locates in the pancreas. We present such a case of pancreatic SFT, along with a review of all reported cases. A 55-year-old man was treated surgically for an asymptomatic pancreatic mass after a rigorous preoperative control. Histologic examination of the resected specimen showed characteristics of an SFT. As only 15 cases of pancreatic SFT have been reported so far, an attempt to compare the cases was considered intriguing. We found that patients with pancreatic SFT were mainly women (81.25%), with a median age of 54 years at the time of diagnosis and a median tumor size of 5.83 cm. Pancreatic SFTs were revealed incidentally in 50% of cases, and all of them showed an enhancement through arterial computed tomography. All tumors were positive for CD34, ten were positive for Bcl-2, and twelve were negative for S100. The diagnosis of this pancreatic tumor is established by a combination of clinical suspicion, imaging procedures and histological findings, and is confirmed by immunohistochemical staining. Although the behavior of SFTs is rather benign, close clinical follow-up is recommended due to a potentially malignant nature.

Capillary Thrombosis in the Skin: A Pathologic Hallmark of Severe/Chronic Rejection of Human Vascularized Composite Tissue Allografts?

BACKGROUND: Vascularized composite tissue allografts (VCA) can undergo rejection, manifesting pathologically with skin changes that form the basis of the Banff 2007 classification of VCA rejection. METHODS: We have followed 10 human VCA recipients (7 with hand allografts, 3 with face allografts) for pathological signs of rejection. All of them developed episodes of acute rejection. Two patients with hand allografts presented in some of their skin biopsies an as yet unreported pathological finding in human VCA, consisting of capillary thromboses (CT) in the upper dermis. RESULTS: Capillary thrombosis was associated with other typical changes of grade II to III VCA rejection, namely, perivascular T cell infiltrates, but not with vascular C4d deposits (in formalin-fixed tissue). Clinically, the lesions presented as red or violaceous (lichenoid) cutaneous maculopapules. The first patient had several episodes of acute rejection during the 7-year follow-up. The second patient developed donor-specific antibodies; some months after CT were first observed, he developed chronic rejection leading to partial amputation of the allograft. Pathological examination of the skin showed graft vasculopathy and occasional C4d deposits in cutaneous capillaries. CONCLUSIONS: Capillary thrombosis seems to be a novel pathologic finding associated with human VCA rejection. Although its mechanism (immunologic vs nonimmunologic) remains unclear, this finding could carry an unfavorable prognostic significance, prompting close monitoring of the patients for severe/chronic rejection.

Ceruminous Adenoma of the External Auditory Canal: A Case Report with Imaging and Pathologic Findings.

Ceruminous adenomas are benign tumors that are rare in humans and present with a nonspecific symptomatology. The treatment of choice is surgical excision. We present an 87-year-old woman who presented with a reddish, tender, round, soft mass of the outer third of the inferior wall of the left external auditory canal, discharging a yellowish fluid upon pressure. Coincidentally, due to her poor general condition, this patient also showed symptoms consistent with chronic otitis media, parotitis, and cervical lymphadenopathy, such as otorrhea, through a ruptured tympanic membrane and swelling of the parotid gland and cervical lymph nodes. The external auditory canal lesion was surgically excised under general anesthesia, utilizing a transmeatal approach. The pathological diagnosis was ceruminous gland adenoma. The tumor was made of tubular and cystic structures and embedded in a fibrous, focally hyalinized stroma. Immunohistochemistry confirmed the presence of two distinct cell populations. The luminal cells expressed keratin 7, while peripheral (basal) cells expressed keratins 5/6, S100 protein, and p63. The apocrine gland-related antigen GCDFP-15 was focally expressed by tumor cells. The postoperative course was uneventful and at the 2-year follow-up no recurrence of the ceruminous adenoma was noted.

PAI-1 and HER2 interaction in advanced breast cancer disease: evidence for added benefit from trastuzumab in HER2-negative patients.

PURPOSE: The urokinase plasminogen activator (uPA) and the plasminogen activator inhibitor 1 (PAI-1) are associated with an aggressive course in breast cancer and are used to determine whether chemotherapy is needed in node-negative patients. The objective of the study was to evaluate the prognostic value of uPA and PAI-1 protein expression in advanced breast cancer patients treated with trastuzumab. METHODS: Formalin-fixed paraffin-embedded tumor tissue samples were retrospectively collected from 230 patients with advanced breast cancer treated with trastuzumab and 130 patients treated with 1st line taxanes. uPA, PAI-1, ER, PgR, HER2 and Ki67 protein expression was evaluated by immunohistochemistry. RESULTS: Central review of HER2 status revealed that only 144 (63 %) of the trastuzumab-treated patients were truly HER2-positive. Median survival was 50.7 months for the HER2-positive and 30.1 months for the HER2-negative patients (p = 0.006) treated with trastuzumab. In multivariate Cox regression analysis of the trastuzumab cohort, a significant interaction was found, in terms of survival, between HER2 status and PAI-1 protein expression in the stroma (Wald's p = 0.002). Positive PAI-1 protein expression in the stroma of HER2-negative patients was associated with lower risk of death (HR 0.35, 95 % CI 0.19-0.65, Wald's p = 0.0008). Such an association was not observed in HER2-positive patients treated with trastuzumab or in the non-trastuzumab (validation) cohorts. CONCLUSIONS: Our results suggest that positive stromal PAI-1 protein expression may identify a subgroup of HER2-negative advanced breast cancer patients who might benefit from treatment with trastuzumab. Further studies are warranted to validate these findings in larger cohorts.