Metastatic solid tumours to the penis: a clinicopathologic evaluation of 109 cases from an international collaboration.

AIMS: To elucidate the spectrum of metastatic tumours to the penis and their clinicopathologic features. METHODS: The databases and files of 22 pathology departments from eight countries on three continents were queried to identify metastatic solid tumours of the penis and to characterize their clinical and pathologic features. RESULTS: We compiled a series of 109 cases of metastatic solid tumours that secondarily involved the penis. The mean patient age at diagnosis was 71 years (range, 7-94 years). Clinical presentation commonly included a penile nodule/mass (48/95; 51%) and localised pain (14/95; 15%). A prior history of malignancy was known in 92/104 (89%) patients. Diagnosis was made mainly on biopsy (82/109; 75%), or penectomy (21/109; 19%) specimens. The most common penile locations were the glans (45/98; 46%) and corpus cavernosum (39/98; 39%). The most frequent histologic type was adenocarcinoma (56%). Most primary carcinomas originated in the genitourinary (76/108; 70%) and gastrointestinal (20/108; 18%) tracts, including prostate (38/108; 35%), urinary bladder (27/108; 25%), and colon/rectum (18/108; 17%). Concurrent or prior extrapenile metastases were identified in 50/78 (64%) patients. Clinical follow-up (mean 22 months, range 0-171 months) was available for 87/109 (80%) patients, of whom 46 (53%) died of disease. CONCLUSION: This is the largest study to date of metastatic solid tumours secondarily involving the penis. The most frequent primaries originated from the genitourinary and gastrointestinal tracts. Metastatic penile tumours usually presented with penile nodules/masses and pain, and they often occurred in the setting of advanced metastatic disease, portending poor clinical outcomes.

Maintenance therapy with ex vivo expanded lymphokine-activated killer cells and rituximab in patients with follicular lymphoma is safe and may delay disease progression.

Anti-cluster of differentiation 20 (CD20) monoclonal antibodies (mAbs) have shown promise in follicular lymphoma (FL) as post-induction therapy, by enhancing antibody-dependent cellular cytotoxicity (ADCC). However, cytotoxic cells are reduced after this treatment. We hypothesised that ex vivo expanded lymphokine-activated killer (LAK) cells administered to FL-remission patients are safe and improve anti-CD20 efficacy. This open, prospective, phase II, single-arm study assessed safety and efficacy of ex vivo expanded LAK cells in 20 FL-remission patients following rituximab maintenance. Mononuclear cells were obtained in odd rituximab cycles and stimulated with interleukin 2 (IL-2) for 8 weeks, after which >5 × 108 LAK cells were injected. Patients were followed-up for 5 years. At the end of maintenance, peripheral blood cells phenotype had not changed markedly. Natural killer, LAK and ADCC activities of mononuclear cells increased significantly after recombinant human IL-2 (rhIL-2) stimulation in all cycles. Rituximab significantly enhanced cytotoxic activity. No patients discontinued treatment. There were no treatment-related serious adverse events. Three patients had progressed by the end of follow-up. After a median (interquartile range) follow-up of 59.4 (43.8-70.9) months, 85% of patients remained progression free. No deaths occurred. Quality-of-life improved throughout the study. Post-induction LAK cells with rituximab seem safe in the long term. Larger studies are warranted to confirm efficacy.

First-line use of rituximab correlates with increased overall survival in late post-transplant lymphoproliferative disorders: retrospective, single-centre study.

This retrospective study evaluates the impact of rituximab on PTLD response and survival in a single-centre cohort. PTLD cases between 1984 and 2009, including heart, kidney, liver and lung transplant recipients, were included. Survival was analysed taking into account the type of PTLD (monomorphic vs. polymorphic), EBV infection status, IPI score, Ann Arbor stage and use of rituximab. Among 1335 transplanted patients, 24 developed PTLD. Median age was 54 yr (range 29-69), median time to diagnosis 50 months (range 0-100). PTLD type was predominantly late/monomorphic (79% and 75%), mostly diffuse large B-cell type. Overall response rate (ORR) was 62% (66% rituximab vs. 50% non-rituximab; P = 0.5). R-CHOP-like regimens were used most frequently (72% of patients treated with rituximab). Median overall survival was 64 months (CI 95% 31-96). OS was significantly increased in patients treated with rituximab (P = 0.01; CI 95% rituximab 58-79 months; non-rituximab 1-30 months). Post-transplant immunosuppression regimen had no effect on survival or time to PTLD, except for cyclosporine A (CyA), which associated with increased time to PTLD (P = 0.02). Rituximab was associated with increased survival in our single-centre series, and it should be considered as first-line therapy for PTLD patients. The possible protective effect of CyA for development of PTLD should be prospectively evaluated.

Scars Run Deep: Problematic Morphology and Immunoprofile of Scars in Renal Oncocytomas.

In some instances, the central scar of renal oncocytoma can demonstrate entrapped cells with unusual morphology and aberrant immunoprofile creating potential diagnostic confusion. Herein, 100 renal oncocytomas containing scars with embedded epithelial cells were identified from 6 institutions, including nephrectomies (64% partial, 36% radical) of similar laterality (left = 51%) and sex distribution (male = 56%), with patient ages ranging from 38 to 86 years (mean = 64.3years) and tumor sizes ranging from 2 to 16 cm (mean = 5.3 cm). Immunohistochemistry was performed on all tumors for KRT7, KIT, vimentin, and CA9 with staining intensity and extensity separately analyzed. Of 4 architectural patterns of cells within the scar, 60% showed tubular pattern. Of 4 cytologies within the scar, flat/elongated (49%) and cuboidal cells (40%) predominated. Within the scar, 62% showed eosinophilic cytoplasm, with 38% showing both cleared and eosinophilic cytoplasm; notably, 79% showed higher grade nuclei than typical oncocytes. A subset of scar cells showed mucinous-like basophilic secretions (19%). Compared to background renal oncocytoma, tumor cells within the scar were more often positive for vimentin, KRT7, and CA9 and more frequently negativity for KIT. Specifically, of the notable "aberrant" immunoprofiles, 79% showed KRT7 positivity/KIT negativity/vimentin positive, 84% showed vimentin positivity/CA9 positivity, and 78% showed KIT negativity/vimentin positivity/CA9 positivity. While encountering scars within renal oncocytomas is not uncommon, what is not well appreciated is the unique morphology and immunohistochemistry of tumor cells within the scar. Comparing tumor morphology and immunoprofile of the scar to the background oncocytoma is helpful to avoid interpretative confusion.

Primary Cutaneous Acral CD8-Positive Lymphoproliferative Disorder: A Case Report With Nonacral Presentation.

In this study, we describe a patient of primary cutaneous acral CD8-positive lymphoproliferative disorder located in a nonacral region. A 65-year-old male presented with an ill-defined lesion of rubbery consistency and a maximum diameter of 2.5 cm localized in the right thigh. Histologically, it was composed of a diffuse dermal infiltration of medium-sized atypical lymphocytes that expressed CD3, CD8, and TIA-1. In addition, a characteristic paranuclear positivity with CD68 was observed. During the follow-up, the patient had a recurrence of the disease in the abdomen with a lesion showing similar morphology and phenotype. To our knowledge, < 20 patients of primary cutaneous acral CD8-positive lymphoproliferative disorder with a nonacral presentation have been described in English literature. Although rare, its identification is essential to differentiate it from other T-cell lymphoma that express CD8 and cytotoxic markers, and whose clinical courses are very aggressive.

Biphasic papillary (biphasic squamoid alveolar) renal cell carcinoma: a clinicopathologic and molecular study of 17 renal cell carcinomas including 10 papillary adenomas.

Biphasic papillary renal cell carcinoma (synonymous with biphasic squamoid alveolar renal cell carcinoma) is considered within the spectrum of papillary renal cell carcinoma (PRCC). With < 70 reported cases of biphasic PRCC, there is limited data on the pathologic spectrum and clinical course. Seventeen biphasic PRCC cases and 10 papillary adenomas with similar biphasic morphology were assessed. The mean age of the biphasic PRCC patients was 62 years (male to female ratio of 1.8:1), from 10 partial nephrectomies, 6 radical nephrectomies, and 1 biopsy. The mean tumor size was 3.6 cm (range 1.6-8 cm), with 24% showing multifocality. Fifteen out of 17 cases were limited to the kidney (one of which was staged as pT2a but had lung metastases at diagnosis) and 2/17 cases were staged as T3a. All tumors showed typical biphasic morphology with an extent of squamoid foci widely variable from 10 to 95%. Emperipolesis was identified in 88% of cases. All biphasic PRCC tested exhibited positivity for PAX8 (16/16), keratin 7 (17/17), EMA (15/15), AMACR (17/17), and vimentin (12/12) in both large and small cells; cyclin D1 was only expressed in the large cells (16/16). The 10 papillary adenomas showed a similar immunoprofile to biphasic PRCC. NGS testing performed on 13 biphasic PRCC revealed 4 (31%) harboring MET SNVs. In 1/5 (20%) papillary adenomas, a pathogenic MET SNV was identified. Biphasic PRCC is rare with a generally similar immunoprofile to "type 1" PRCC but with notable strong positivity for cyclin D1 in the large cell component. Although most of the biphasic PRCC cases were of small size, low stage, and with an indolent behavior, one patient had metastatic disease and one patient died of the disease.

The 1000 Mitoses Project: A Consensus-Based International Collaborative Study on Mitotic Figures Classification.

Introduction. The identification of mitotic figures is essential for the diagnosis, grading, and classification of various different tumors. Despite its importance, there is a paucity of literature reporting the consistency in interpreting mitotic figures among pathologists. This study leverages publicly accessible datasets and social media to recruit an international group of pathologists to score an image database of more than 1000 mitotic figures collectively. Materials and Methods. Pathologists were instructed to randomly select a digital slide from The Cancer Genome Atlas (TCGA) datasets and annotate 10-20 mitotic figures within a 2 mm2 area. The first 1010 submitted mitotic figures were used to create an image dataset, with each figure transformed into an individual tile at 40x magnification. The dataset was redistributed to all pathologists to review and determine whether each tile constituted a mitotic figure. Results. Overall pathologists had a median agreement rate of 80.2% (range 42.0%-95.7%). Individual mitotic figure tiles had a median agreement rate of 87.1% and a fair inter-rater agreement across all tiles (kappa = 0.284). Mitotic figures in prometaphase had lower percentage agreement rates compared to other phases of mitosis. Conclusion. This dataset stands as the largest international consensus study for mitotic figures to date and can be utilized as a training set for future studies. The agreement range reflects a spectrum of criteria that pathologists use to decide what constitutes a mitotic figure, which may have potential implications in tumor diagnostics and clinical management.

Adult hepatoblastoma.

Adult hepatoblastoma (AHB) is a very rare tumor, having been described 45 cases up to June 2012. In contrast to HB in infancy (IHB), it has poor prognosis. We present the case of a 37-year-old asymptomatic woman who consulted for a large -12 cm diameter- mass involving segments 5 and 6 of the liver, and alfa-fetoprotein of 1,556,30 UI/mL. A bisegmentectomy was carried out. The microscopic study confirmed the AHB diagnosis, revealing the presence of epithelial cells forming clusters, trabecular patterns and tubules. The patient died on the 10th postoperative month due to progression disease.The Wnt/Beta-Catenin signaling pathway mutation has been reported and associated with a poor prognosis in IHB. Due to the AHB poor prognosis, seems reasonable to introduce the therapeutic regimens described in children who have a better outcome.

Angiomatoid Fibrous Histiocytoma of the Chest Wall Protruding into the Thoracic Cavity Mimicking Metastasis in a Patient with Breast Cancer.

Angiomatoid fibrous histiocytoma (AFH) is a rare soft tissue tumor of intermediate malignancy and uncertain differentiation. To date, only four patients diagnosed with AFH located in the chest wall have been described. Herein, we describe a 44-year-old woman diagnosed with breast infiltrating lobular carcinoma. During the imaging study with positron emission tomography-computerized tomography scan, a 4 cm solid lesion located in the chest wall was identified. Fine-needle aspiration followed by surgical excision with intraoperative frozen section study was performed. The combined histomorphologic, immunohistochemical, and molecular findings confirmed the diagnosis of AFH. In this report, we describe, to the best of our knowledge, the first patient with synchronous AFH and breast cancer.

Metastatic solid tumors to the testis: a clinicopathologic evaluation of 157 cases from an international collaboration.

To elucidate the spectrum of metastatic solid tumors to the testis and their clinicopathologic features. The databases and files of 26 pathology departments from 9 countries on 3 continents were surveyed to identify metastatic solid tumors to the testis and to characterize their clinicopathologic features in detail. We compiled a series of 157 cases of metastatic solid tumors that secondarily involved the testis. The mean patient age at diagnosis was 64 years (range, 12-93 years). Most patients (127/144; 88%) had clinical manifestation of the disease, with testicular mass/nodule (89/127; 70%) being the most common finding. The main mechanism of testicular involvement was metastasis in 154/157 (98%) cases. Bilateral testicular involvement was present in 12/157 (8%) patients. Concurrent or prior extratesticular metastases were present in 78/101 (77%) patients. The diagnosis was made mainly in orchiectomy specimens (150/157; 95%). Different types of carcinomas (138/157; 87%), most commonly adenocarcinoma (72/157; 46%), were the most common malignancies. The most common primary carcinomas included prostatic (51/149; 34%), renal (29/149; 20%), and colorectal (13/149; 9%). Intratubular growth was identified in 13/124 (11%) cases and paratesticular involvement was found in 73/152 (48%) cases. In patients with available follow-up (110/157; 70%), more than half (58/110; 53%) died of disease. In this largest series compiled to date, we found that most secondary tumors of the testis represent metastases from the genitourinary and gastrointestinal tract carcinomas and typically occur in the setting of disseminated disease.

Concomitant lymphoplasmacytic lymphoma, multiple myeloma, and amyloidosis: A diagnostic and therapeutic challenge.

We report a case based on simultaneous occurrence of Waldenström macroglobulinemia, myeloma and amyloidosis as a collision neoplasm. The strangeness and severity of the case presented a diagnostic and therapeutic challenge, which required individualised treatment and close follow-up to achieved stringent complete response.

COVID-19 Pulmonary Pathology: The Experience of European Pulmonary Pathologists throughout the First Two Waves of the Pandemic.

Autoptic studies of patients who died from COVID-19 constitute an important step forward in improving our knowledge in the pathophysiology of SARS-CoV-2 infection. Systematic analyses of lung tissue, the organ primarily targeted by the disease, were mostly performed during the first wave of the pandemic. Analyses of pathological lesions at different times offer a good opportunity to better understand the disease and how its evolution has been influenced mostly by new SARS-CoV-2 variants or the different therapeutic approaches. In this short report we summarize responses collected from a questionnaire survey that investigated important pathological data during the first two pandemic waves (spring-summer 2020; autumn-winter 2020-2021). The survey was submitted to expert lung pathologists from nine European countries involved in autoptic procedures in both pandemic waves. The frequency of each lung lesion was quite heterogeneous among the participants. However, a higher frequency of pulmonary superinfections, both bacterial and especially fungal, was observed in the second wave compared to the first. Obtaining a deeper knowledge of the pathological lesions at the basis of this complex and severe disease, which change over time, is crucial for correct patient management and treatment. Autoptic examination is a useful tool to achieve this goal.

Altered transcription factor E3 expression in unclassified adult renal cell carcinoma indicates adverse pathological features and poor outcome.

OBJECTIVES: To evaluate the clinical and pathologic features and the prognostic relevance of unclassified RCC with -TFE3 over-expression in our adult series. Recent studies suggest that renal cell carcinomas (RCCs) associated with the newly recognized Xp11.2 translocation (transcription factor E3 [TFE3] gene fusions) can be found among adults with RCC showing a very aggressive disease-course. MATERIAL AND METHODS: We evaluated tumour specimens from 25 patients with unclassified RCC morphology out of 298 RCCs in the last 12 years in a tertiary academic centre. Immunohistochemistry was performed using monoclonal antibody for TFE3 C-terminal section, taking nuclear label into consideration. RT-PCR technique was performed for ASPL-TFE3 gene fusion on two tumours with available frozen tissue. RESULTS: Of the 25 cases analyzed, 8 (32%) showed positivity for TFE3 and 17 were negative for TFE3 staining. Two tumors with ASPL-TFE3 gene fusion also showed TFE3 over-expression. Fifty percent of the positive patients had lymph node metastatic disease, whereas only one TFE3-negative patient (5.8%) showed evidence of lymph node spread and cava thrombus at diagnosis. Of the TFE3-positive patients, three had a vena cava thrombus (37.5%). Seven of the eight positive cases (87.5%) were diagnosed with a high Fuhrman grade (III/IV). In comparison, five of 17 (29.4%) TFE3-negative patients had a high Fuhrman grade. Five of eight TFE3-positive patients relapsed rapidly at 3 month follow-up; conversely none of the negative cases relapsed. At 36-month mean follow-up, 5-year cancer-specific survival was 15.6% for TFE3-positive patients and 87.5% for TFE3-negative patients (P < 0.001). CONCLUSION: Patients with unclassified RCC and TFE3 positivity have a grim prognosis due to their advanced stage at presentation and aggressive biologic features compared with the TFE3-negative unclassified RCC cases.

Association of steroid and xenobiotic receptor (SXR) and multidrug resistance 1 (MDR1) gene expression with survival among patients with invasive bladder carcinoma.

UNLABELLED: What's known on the subject? and What does the study add? SXR and MDR1 are known as responsible for chemo and radiotherapy resistance in some cancers, like kidney cancer (MDR1). Invasive bladder cancer is an aggressive disease, with different behaviour upon its tumoral stage, and also within the same tumoral stage, therefore molecular markers are sought. This study shows a new molecular marker, which has shown as a predictor for bad prognosis cancers, therefore, allowing us for a better patient selection for aggressive therapies. OBJECTIVE: To investigate the prognostic value of steroid and xenobiotic receptor (SXR) and multidrug resistance 1 (MDR1) gene expression in relation to survival among patients with invasive bladder cancer. PATIENTS AND METHODS: The prospective study included 67 patients diagnosed with invasive bladder cancer and treated with radical cystectomy at one of two institutions. SXR and MDR1 gene expression was assessed by real-time quantitative polymerase chain reaction (RT-PCR) in tumoral and normal tissue from frozen surgical specimens. RESULTS: Patients were followed for a mean of 29 months; 31 patients (46%) had progression. In univariate analysis, significant predictors of overall survival (OS) were pathological stage, lymph node (LN) status, histological grade, vascular-lymphatic invasion, and SXR expression. In multivariate analysis, independent predictors of OS were LN status (odds ratio [OR], 2.96; P=0.034), vascular-lymphatic invasion (OR, 2.50; P=0.029), and SXR expression (OR, 1.05, P=0.03). Among the 51 patients with negative LNs (pN0), univariate predictors of OS were SXR expression, MDR1 expression, and pathological stage. In multivariate analysis, SXR expression (OR, 1.06; P=0.01) and MDR1 expression (OR, 3.27; P=0.03) were independently associated with survival. Within the pN0 group, patients with SXR expression had shorter progression-free survival than did those without expression (P=0.004). This association persisted in the N0 subgroup with stage pT3-pT4 disease (P=0.028). However, in the pN1 group SXR expression did not have any influence. CONCLUSIONS: For patients with invasive bladder cancer, SXR expression has value as a predictor of survival independent of the standard pathological predictors. Its maximum importance appears to be in patients with stage pT3-pT4 pN0 disease.

Prostatic leiomyoma. Case report.

OBJECTIVE: We try to show the relevance of this rare pathology and to set its importance in the differential diagnosis of prostate masses. METHODS: We report a case and perform a search in the MEDLINE database of the series described up to the date. RESULTS: Prostatic leiomyoma is a extremely rare anatomopathological finding, though the appearance of a glandular hyperplasia with small areas of leiomyomatous growth is more common. Up to date there are just a hundred cases described. They are benign mesenchymal tumors without evidence of disease recurrence after surgery. When they present symptomatology, they emulate benign hyperplasia with urinary tract infections. Although it has benign nature, surgical intervention is indicated when severe clinical symptoms appear. CONCLUSIONS: The recognition of this benign entity and the distinction from other neoplasias has important therapeutic and prognostic implications. Imaging techniques and pathological analysis are crucial for this reason. When an unusual prostatic mass is detected, the leiomyoma must be included in the differential diagnosis.

Diagnostic approach in TFE3-rearranged renal cell carcinoma: a multi-institutional international survey.

Transcription factor E3-rearranged renal cell carcinoma (TFE3-RCC) has heterogenous morphologic and immunohistochemical (IHC) features.131 pathologists with genitourinary expertise were invited in an online survey containing 23 questions assessing their experience on TFE3-RCC diagnostic work-up.Fifty (38%) participants completed the survey. 46 of 50 participants reported multiple patterns, most commonly papillary pattern (almost always 9/46, 19.5%; frequently 29/46, 63%). Large epithelioid cells with abundant cytoplasm were the most encountered cytologic feature, with either clear (almost always 10/50, 20%; frequently 34/50, 68%) or eosinophilic (almost always 4/49, 8%; frequently 28/49, 57%) cytology. Strong (3+) or diffuse (>75% of tumour cells) nuclear TFE3 IHC expression was considered diagnostic by 13/46 (28%) and 12/47 (26%) participants, respectively. Main TFE3 IHC issues were the low specificity (16/42, 38%), unreliable staining performance (15/42, 36%) and background staining (12/42, 29%). Most preferred IHC assays other than TFE3, cathepsin K and pancytokeratin were melan A (44/50, 88%), HMB45 (43/50, 86%), carbonic anhydrase IX (41/50, 82%) and CK7 (32/50, 64%). Cut-off for positive TFE3 fluorescent in situ hybridisation (FISH) was preferably 10% (9/50, 18%), although significant variation in cut-off values was present. 23/48 (48%) participants required TFE3 FISH testing to confirm TFE3-RCC regardless of the histomorphologic and IHC assessment. 28/50 (56%) participants would request additional molecular studies other than FISH assay in selected cases, whereas 3/50 participants use additional molecular cases in all cases when TFE3-RCC is in the differential.Optimal diagnostic approach on TFE3-RCC is impacted by IHC and/or FISH assay preferences as well as their conflicting interpretation methods.

Pulmonary pathology and COVID-19: lessons from autopsy. The experience of European Pulmonary Pathologists.

Since its initial recognition in December 2019, Coronavirus disease 19 (COVID-19) has quickly spread to a pandemic infectious disease. The causative agent has been recognized as a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), primarily affecting the respiratory tract. To date, no vaccines are available nor any specific treatment. To limit the number of infections, strict directives have been issued by governments that have been translated into equally rigorous guidelines notably for post-mortem examinations by international and national scientific societies. The recommendations for biosafety control required during specimen collection and handling have strongly limited the practice of autopsies of the COVID-19 patients to a few adequate laboratories. A full pathological examination has always been considered an important tool to better understand the pathophysiology of diseases, especially when the knowledge of an emerging disorder is limited and the impact on the healthcare system is significant. The first evidence of diffuse alveolar damage in the context of an acute respiratory distress syndrome has now been joined by the latest findings that report a more complex scenario in COVID-19, including a vascular involvement and a wide spectrum of associated pathologies. Ancillary tools such as electron microscopy and molecular biology used on autoptic tissue samples from autopsy are also significantly contributing to confirm and/or identify new aspects useful for a deeper knowledge of the pathogenetic mechanisms. This article will review and summarize the pathological findings described in COVID-19 until now, chiefly focusing on the respiratory tract, highlighting the importance of autopsy towards a better knowledge of this disease.

#EBUSTwitter: Novel Use of Social Media for Conception, Coordination, and Completion of an International, Multicenter Pathology Study.

CONTEXT.­: Social media sites are increasingly used for education, networking, and rapid dissemination of medical information, but their utility for facilitating research has remained largely untapped. OBJECTIVE.­: To describe in detail our experience using a social media platform (Twitter) for the successful initiation, coordination, and completion of an international, multi-institution pathology research study. DESIGN.­: Following a tweet describing a hitherto-unreported biopsy-related histologic finding in a mediastinal lymph node following endobronchial ultrasound-guided transbronchial needle aspiration, a tweet was posted to invite pathologists to participate in a validation study. Twitter's direct messaging feature was used to create a group to facilitate communication among participating pathologists. Contributing pathologists reviewed consecutive cases of mediastinal lymph node resection following endobronchial ultrasound-guided transbronchial needle aspiration and examined them specifically for biopsy site changes. Data spreadsheets containing deidentified data and digital photomicrographs of suspected biopsy site changes were submitted via an online file hosting service for central review by 5 pathologists from different institutions. RESULTS.­: A total of 24 pathologists from 14 institutions in 5 countries participated in the study within 143 days of study conception, and a total of 297 cases were collected and analyzed. The time interval between study conception and acceptance of the manuscript for publication was 346 days. CONCLUSIONS.­: To our knowledge, this is the first time that a social media platform has been used to generate a research idea based on a tweet, recruit coinvestigators publicly, communicate with collaborating pathologists, and successfully complete a pathology study.

Metastatic clear cell renal cell carcinoma to the thyroid gland: A clinico-pathological and immunohistochemical study of 8 cases and review of the literature.

When a patient with a previous history of neoplasm presents with a thyroid lesion, the possibility of it being metastatic should always be considered. In this series, we present the clinicopathological and immunohistochemical features of the thyroid metastases diagnosed in our department over the past 30 years. Here we present eight thyroidal metastases from clear cell renal cell carcinoma (ccRCCC), including a tumor to tumor metastasis, the patients being 2 men and 6 women with a median age of 62 years. The majority had a past history of goiter and a single and palpable metastasis. In one patient the thyroid metastases were the first sign of the ccRCCC. In the available cases, the metastasis showed positivity to PAX8 and CAIX and negativity to TTF1 and thyroglobulin. The median time from the detection of the primary renal tumor to thyroid metastasis and from thyroidectomy to last follow up were 84.17 and 54.50 months, respectively. After a median follow up of 158.50 months none of the patients had died from ccRCCC. Renal cell carcinoma (RCC) is the most frequent malignant neoplasm of the kidney and its incidence has increased over recent decades. In a clinical series, up to 1-3% of the oncologic thyroidectomies were due to thyroid metastases and the most frequent metastasizing tumor was RCC, followed by lung and breast cancer.