The Combined Immunohistochemical Expression of GLI1 and BCOR in Synovial Sarcomas for the Identification of Three Risk Groups and Their Prognostic Outcomes: A Study of 52 Patients.

Synovial sarcoma (SS) is a rare soft-tissue tumor characterized by a monomorphic blue spindle cell histology and variable epithelial differentiation. Morphologically, SSs may be confused with other sarcomas. Systemic treatment is more effective for patients with high-risk SSs, patients with advanced disease, and younger patients. However, further studies are required to find new prognostic biomarkers. Herein, we describe the morphological, molecular, and clinical findings, using a wide immunohistochemical panel, of a series of SS cases. We studied 52 cases confirmed as SSs by morphological diagnosis and/or molecular studies. Clinical data (gender, age, tumor size, tumor location, resection margins, adjuvant treatment, recurrences, metastasis, and survival) were also retrieved for each patient. All the available H&E slides were examined by four pathologists. Three tissue microarrays (TMAs) were constructed for each of the tumors, and a wide immunohistochemical panel was performed. For time-to-event variables, survival analysis was performed using Kaplan-Meier curves and log-rank testing, or Cox regression. Statistical significance was considered at p < 0.05. The mean age of our patients was 40.33, and the median was 40.5 years. We found a predominance of males versus females (1.7:1). The most frequent morphological subtype was monophasic. TRPS1, SS18-SSX, and SSX-C-terminus were positive in 96% of cases. GLI1 expression was strong in six and focal (cytoplasmic) in twenty patients. Moreover, BCOR was expressed in more than half of SSs. Positive expression of both proteins, BCOR and GLI1, was correlated with a worse prognosis. Multivariate analysis was also performed, but only BCOR expression appeared to be significant. The combination of GLI1 and BCOR antibodies can be used to group SSs into three risk groups (low, intermediate, and high risk). We hypothesize that these findings could identify which patients would benefit from receiving adjuvant treatment and which would not. Moreover, these markers could represent therapeutic targets in advanced stages. However, further, larger series of SSs and molecular studies are necessary to corroborate our present findings.

The percentage of mesorectal infiltration as a prognostic factor after curative surgery for pT3 rectal cancer.

AIM: The aim of this study is to evaluate the prognostic value of a novel variable - the percentage of mesorectal infiltration (PMI) - in pT3 rectal cancer. METHOD: A cohort of 241 patients with pT3 rectal adenocarcinoma, operated on between February 2002 and May 2019, was selected for the analysis. Data concerning patient, treatment and tumour characteristics were collected. The depth of mesorectal infiltration (DMI) and the distance between the deepest invasion and the circumferential resection margin (CRM) were measured. The PMI was calculated using a formula combining these parameters. RESULTS: Neoadjuvant therapy was administered in 33.2% of cases. A complete mesorectal excision was achieved in 74% of patients. The CRM was affected in 24 patients (9.9%). The 5-year actuarial local recurrence (LR), overall recurrence (OR) and overall survival (OS) rates were 7.5%, 22.9% and 72.4%, respectively. The PMI was significantly associated with worse oncological outcomes regarding LR (p = 0.009), OR (p = 0.001) and OS (p = 0.016) rates. A cut-off value of PMI >60% had the highest specificity (80%) for LR (p = 0.026), OR (p = 0.04) and OS (p = 0.07). CONCLUSION: The PMI has an adverse prognostic impact on the oncological results following surgery for pT3 rectal cancer. It allows prediction of the risk of both LR and distant recurrence with higher accuracy than the DMI or the distance to the CRM. A PMI >60% may be used as a cut off value while subclassifying pT3 rectal tumours. It may influence decision-making while establishing adjuvant treatment and the follow-up schedule.

Intimal Sarcoma with MDM2/CDK4 Amplification and p16 Overexpression: A Review of Histological Features in Primary Tumor and Xenograft, with Immunophenotype and Molecular Profiling.

Intimal sarcomas (IS) are rare malignant mesenchymal tumors arising in large blood vessels of the systemic and pulmonary circulation and also in the heart. They are morphologically similar to other spindle cell, poorly differentiated sarcomas. The prognosis is poor and depends mainly on surgical options. Three cases of IS were collected from two institutions. Clinical data were retrieved and histological study was performed. A wide immunohistochemical panel was analyzed. FISH of MDM2 gene was performed, and a molecular study with NGS was implemented in all cases. The mean age of our cases was 54 years. Histologically, the tumors presented a diffuse growth pattern with heterogeneous atypical epithelioid or spindle cells and extensive thrombosed areas. All cases presented intense immunoexpression for MDM2, CDK4, CD117, c-myc, PDGFRA, and p16. PDGFRA, HTERT, and pan-TRK gained expression, while p16 lost intensity, being weaker in both the local recurrences and xenografts. The three cases showed amplification of MDM2 by FISH. NGS analysis revealed amplifications in the CDK4, PDGFRA, and KIT genes, together with BRAF mutation and KRAS amplification. P16 was expressed in all cases, losing intensity in local recurrence and xenografts. Two new alterations, a BRAF mutation and a KRAS amplification, were detected by NGS in different tumors, opening up new therapeutic options for these patients.

Evaluation of Alternative Risk Stratification Systems in a Large Series of Solitary Fibrous Tumors with Molecular Findings and Ki-67 Index Data: Do They Improve Risk Assessment?

The clinical evolution of solitary fibrous tumors (SFTs) is often uncertain and several risk stratification systems (RSS) have been proposed. The Demicco et al. RSS is the most frequently implemented. In this study we aim to validate two alternative RSS (Sugita et al. and G-Score) using results for the Demicco RSS from a previous study of 97 SFTs. In addition, we aim to determine whether reclassified cases had any distinctive molecular features. As the Sugita et al. system substitutes mitotic count with Ki-67 index we also investigated whether Ki-67 results for tissue microarrays are comparable to those obtained using whole tissue sections. In the present study we detected that many cases classified by Demicco RSS as low-risk were reclassified as intermediate risk using the new system (G-score RSS). Kaplan-Meier survival plots for G-Score RSS showed that the low-risk and intermediate-risk SFTs had a similar evolution that contrasted with the more aggressive high-risk group. Moreover, the similar evolution in both low and intermediate-risk groups occurred despite the G-score system being stricter in classifying low-risk tumors. We observed that Sugita RSS does not provide any better risk stratification in comparison with the Demicco RSS, and testing both RSS in our series produced similar Kaplan-Meier survival data. We found some discordant results when comparing whole sections and the corresponding tissue microarrays samples, finding the hotspot areas easier to locate in whole sections. Forty-one SFTs with initial low-risk assigned by the Demicco RSS were reclassified as intermediate-risk by G-score finding both TP53 and HTER mutations in four cases, only HTER mutation in 11 cases, and only TP53 mutation in 2 cases. All six cases of SFT classified as high-risk by both the Demicco and G-score RSS suffered recurrence/metastasis, and half showed both TP53 and HTER mutations. Five SFTs were categorized as low-risk by both Demicco and G-score, of which 4 cases revealed HTER mutation. Regarding the outcome of these 5 patients, two were lost to follow-up, and one of the remaining three patients suffered recurrence. We believe that although the presence of both TP53 and HTER mutations may confer or be related to poor evolution, the isolated presence of HTER mutation alone would not necessarily be related to poor outcome. The G-score RSS more accurately identified low-risk patients than the other two risk models evaluated in the present series. Late recurrence/metastasis may occasionally be observed even in low-risk SFTs categorized by stricter classification systems such as the G-score RSS. These findings support the possibility that additional, as yet unknown factors may influence the clinical evolution of SFTs. In conclusion, given the possibility of late recurrence, long-term follow-up is recommended for all SFT patients, even in cases classified as low risk by the stricter G-score system. An integration of clinical, radiological, pathological, and molecular findings may improve SFT risk stratification and better predict patient outcome.

Solitary Fibrous Tumor: Integration of Clinical, Morphologic, Immunohistochemical and Molecular Findings in Risk Stratification and Classification May Better Predict Patient outcome.

Although solitary fibrous tumors (SFTs) have an unpredictable evolution, some specific clinicopathologic factors have been associated with the final outcome. We retrieved clinical, pathological and molecular data of 97 patients with a histological diagnosis of SFT and Signal transducer and activator of transcription 6 (STAT6) positivity. We retrospectively studied the pathological factors predictive of recurrence/metastasis and compared them with the clinical outcome. A wide immunohistochemical study and molecular analysis to detect NAB2/STAT6 gene fusion, tumor protein-53 (TP53) and/or (telomerase reverse transcriptase) TERT promotor mutation were performed. The risk of metastasis was calculated using the Demicco risk stratification system (RSS). The results were combined and examined to assess the accuracy of risk stratification and classification. The most common location was in non-extremities; 66% were located in soft tissue or subcutaneous areas and 92.8% in deep locations. On microscopic analysis, 38.1% of tumors revealed hypercellularity with a predominant patternless and/or hemangiopericytic growth pattern; 13.4% had ≥4 mitoses/10HPF; 16.5% showed necrosis, and almost half the tumors showed at least focal myxoid areas. Dedifferentiation was observed in three tumors. Immunomarker expression in SFTs was as follows: CD34 92.9%, CD99 57.1%, Bcl2 67.9%, neuroendocrine markers (at least 1) 25.7%, Desmin 14.3%, CK(AE1/AE3) 3%, Apoptotic Protease Activating Factor (APAF-1) 87% and finally Ki-67 ≥ 10% in 14.4%. The NAB2/STAT6 gene fusion was detected in 50 tumors. After a median follow-up of 90 months, 9.3% recurred, 11.3% metastasized, 10.3% died of disease and 76.2% were free of disease. TERT mutations were detected in 40.6% of the SFTs; the TP53 mutation was detected in 17%, and only 9.3% showed both mutations. According to the Demicco RSS, 6.1%, 11.3% and 82.4% of the tumors were classified as high, intermediate or low-risk of metastasis, respectively. All high-risk tumors had ≥4 mitoses/10HPF, necrosis, Ki-67 ≥ 10, HTER and/or TP53 mutation and poor evolution. The intermediate risk SFTs with worse evolution displayed the HTER mutation. Almost all low-risk tumors had a favorable evolution, although four showed at least one adverse factor (Ki-67 ≥ 10, ≥4 mitoses/10HPF or high tumor size) and had a worse evolution. An integration of clinical, morphologic, immunohistochemical and molecular findings may improve risk stratification and classification and better predict patient outcome. The unfavorable course seems to be more frequent in high-risk SFTs, although it is not exceptional in low-risk SFTs either; hence, a long-term follow-up is required independently of the assigned risk stratification score. The inclusion of molecular findings in risk stratification systems could improve the precision in the classification of SFTs, especially those of intermediate risk. Future studies will be required to determine the most effective way to incorporate molecular analyses into RSS on SFTs. The coexistence of several adverse factors such as ≥4 mitoses/10HPF, necrosis, Ki-67 ≥ 10%, mutations in HTER and/or p53 may suggest a closer clinical follow-up regardless of the histological appearance of the tumor.

A Proposal for Novel Standards of Histopathology Reporting for D3 Lymphadenectomy in Right Colon Cancer: The Mesocolic Sail and Superior Right Colic Vein Landmarks.

BACKGROUND: Strong agreement exists concerning the standards of pathologic reporting for total mesorectal excision and complete mesocolic excision. It represents a quality standard that correlates with survival. However, no agreed standards of reporting are available to define D3 lymphadenectomy for right colectomy. OBJECTIVE: The purpose of this study was to define anatomopathological standards of specimen quality obtained from the surgical specimen when an oncologic right hemicolectomy with D3 lymphadenectomy has been correctly performed. DESIGN: This study was conducted in 2 different phases. The first part consisted of a cadaver-based study of right colon anatomy, and the second part consisted of a prospective assessment of a series of surgical specimens obtained after right hemicolectomy for cancer. SETTINGS: The anatomic phase of the study was performed in collaboration with the University of Valencia Department of Anatomy and Embryology. The second part was performed at a colorectal unit of a tertiary hospital. PATIENTS: Seventeen cadavers were used for the first phase, and 65 surgical specimens were examined for the second part of the study. MAIN OUTCOME MEASURES: In each specimen, the pathologists looked for anatomic structures defined as markers of quality standards of the D3 lymphadenectomy during the first phase. Specimens were classified as complete, partial, and incomplete D3 lymphadenectomy. RESULTS: Twenty percent of specimens were classified as incomplete D3 lymphadenectomy, 31% as partial, and 49% as complete. A median number of 14 (6-64), 22 (11-47), and 29 (14-55) lymph nodes were isolated (p = 0.01). Similarly, the median numbers of lymph nodes isolated in the area of D3 lymphadenectomy were 0 in incomplete, 1 (0-5) in Partial, and 3 (0-8) in Complete D3 lymphadenectomy specimens (p = 0.0001). LIMITATIONS: A large multicenter study with adequate power is needed. CONCLUSIONS: We propose the right mesocolic sail and trunk of superior right colic vein as new and reproducible anatomopathologic standards of D3 lymphadenectomy in oncologic right hemicolectomy. See Video Abstract at http://links.lww.com/DCR/B149. PROPUESTA PARA NUEVOS ESTÁNDARES HISTOPATOLÓGICOS EN LA LINFADENECTOMÍA D3 EN EL CÁNCER DE COLON DERECHO: LA VELA MESOCÓLICA Y LA VENA CÓLICA DERECHA SUPERIOR: Existe un claro acuerdo sobre los estándares de calidad patológicos para la escisión total del mesorrecto y la escisión completa del mesocolon. Son considerados "estándar de calidad" que se correlaciona con la supervivencia. Sin embargo, no se dispone de estándares de calidad para definir la linfadenectomía D3, en la colectomía derecha.Definir los estándares anatomopatológicos de calidad obtenidos de una muestra quirúrgica, cuando se ha realizado correctamente una hemicolectomía derecha oncológica, con linfadenectomía D3.Dos fases diferentes. La primera parte consistió en un estudio basado en la anatomía del colon derecho, realizado en cadáveres, y la segunda parte consistió en una evaluación prospectiva de una serie de muestras quirúrgicas obtenidas después de la hemicolectomía derecha para cáncer.La fase anatómica del estudio se realizó en colaboración con el Departamento de Anatomía y Embriología de la Universidad de Valencia. La segunda parte se realizó en la Unidad Colorrectal de un hospital terciario.Se utilizaron diecisiete cadáveres para la primera fase y se examinaron 65 muestras quirúrgicas para la segunda parte del estudio.En cada muestra, los patólogos buscaron estructuras anatómicas definidas, como marcadores de los estándares de calidad de la linfadenectomía D3, durante la primera fase. Las muestras se clasificaron como linfadenectomía D3 completa, parcial e incompleta.El veinte por ciento de las muestras se clasificaron como "Linfadenectomía D3 Incompleta", el 31% como "Parcial" y el 49% como "Completa." Se aisló una media de 14 (6-64), 22 (11-47) y 29 (14-55) ganglios linfáticos respectivamente (p = 0,01). Del mismo modo, el número medio de ganglios linfáticos aislados en el área de la linfadenectomía D3 fue 0 en "Incompleta", 1 (0-5) en "Parcial" y 3 (0-8) en muestras de "Linfadenectomía D3 Completa" (p = 0,0001).Se necesita un estudio multicéntrico con potencia adecuada.Proponemos la vela mesocólica derecha y el tronco de la vena cólica derecha superior, como estándares anatomopatológicos nuevos y reproducibles de linfadenectomía D3, en hemicolectomía derecha oncológica. Consulte Video Resumen en http://links.lww.com/DCR/B149.

Controversial issues in soft tissue solitary fibrous tumors: A pathological and molecular review.

The clinical evolution of solitary fibrous tumor (SFT) remains unclear. Although various clinical, morphological and molecular criteria may indicate increased risk of malignancy, some SFT can still progress despite having a clearly benign appearance. Various risk stratification systems have been proposed, but unfortunately they are not sufficient to precisely determine the malignant potential. In this review, we discuss current knowledge on SFT, focusing on the following controversial issues: (i) the diverse morphologic spectrum: 'the great simulator;' (ii) malignant transformation or dedifferentiation; (iii) current risk stratification systems; and (iv) molecular factors associated with clinical evolution. The morphological spectrum of SFT and the list of differential diagnoses continue to expand. Both have increased considerably since the first descriptions of specific molecular alterations. A classification of malignant SFT should not be based on histology alone. The correlation of all pathological and molecular factors is recommended; its inclusion in risk stratification systems may help to improve diagnosis and prognosis.

Prognostic Impact of pT Stage and Peritoneal Invasion in Locally Advanced Colon Cancer.

BACKGROUND: TNM stage has been identified as an independent variable for local recurrence and survival after colon cancer resection. It is still unclear whether peritoneal invasion (pT4a) is a risk factor for adverse oncologic outcome or whether these patients have better results compared with contiguous organs infiltration (pT4b), independent from nodal status (pN). OBJECTIVE: The purpose of this study was to analyze whether peritoneal invasion is an independent risk factor for worse oncologic outcome after curative colon cancer resection. DESIGN: This was a retrospective analysis with multivariate regression of a prospective database, according to Strengthening the Reporting of Observational Studies in Epidemiology Statement. SETTINGS: The study was conducted in a specialized colorectal unit of a tertiary hospital. PATIENTS: A consecutive series of pT3-pT4a-pT4b patients with colon cancer who underwent curative surgery (1993-2010) were included, and patients with metastasis were excluded. MAIN OUTCOME MEASURES: A multivariate Cox regression analysis was performed to assess independent risk factors for 5-year local recurrence, peritoneal carcinomatosis-like recurrence, disease-free survival, and cancer-specific survival. RESULTS: A total of 1010 patients were analyzed (79.3% pT3, 9.9% pT4a, and 10.8% pT4b). At diagnosis, 22.0% had obstructive symptoms, and 10.5% had bowel perforation. A total of 72.2% of the surgeries were elective, and in 15.6% en bloc resection of contiguous organs was performed. Median follow-up was 62 months (38-100 mo). For the whole group, 5-year actuarial rates were 8.8% for local recurrence, 2.5% for peritoneal carcinomatosis, 75.5% for disease-free survival, and 81.8% for cancer-specific survival. At multivariate analysis, pT4a stage was an independent risk factor for local recurrence (p = 0.002; HR = 3.1), peritoneal carcinomatosis (p = 0.02; HR = 4.9), worse disease-free survival (p = 0.002; HR = 1.9), and cancer-specific survival (p = 0.001; HR = 2.2). When considering only the 566 patients with ≥12 nodes identified, T stage was still associated with higher local recurrence (p = 0.04) and carcinomatosis rate (p = 0.04), as well as worse disease-free (p = 0.009) and cancer-specific survival (p = 0.014). LIMITATIONS: This was a retrospective, single-center study. CONCLUSIONS: pT4a stage is an independent risk factor for worse oncologic outcome after curative colon cancer resection compared with pT3 and pT4b stages. The current pT4a-pT4b classification should be reconsidered. Of note, even in pT4a patients, 5-year carcinomatosis rate does not exceed 6%. See Video Abstract at http://links.lww.com/DCR/A926.

Chemokine Expression Is Involved in the Vascular Neogenesis of Ewing Sarcoma: A Preliminary Analysis of the Early Stages of Angiogenesis in a Xenograft Model.

BACKGROUND: Ewing sarcoma (EWS) is the second most common bone cancer in pediatric patients. Angiogenesis is a major factor for tumor growth and metastasis. Our aim was to carry out a histological, immunohistochemical, and molecular characterization of the neovascularization established between xenotransplanted tumors and the host during the initial phases of growth in nude mice in three angiogenesis experiments (ES2, ES3, and ES4). METHODS: The original human EWS were implanted subcutaneously on the backs of three nude mice. Tumor pieces 3 mm-4 mm in size from early passages of Nu432, Nu495, and Nu471 were also implanted subcutaneously on the backs of three sets (ES2, ES3, and ES4) of athymic Balb-c nude mice (n = 14 each). The animals were sacrificed at 24, 48, and 96 hours and at 7, 14, 21, and 28 days after implantation to perform histological, immunohistochemical, and molecular studies (neovascularization experiments). RESULTS: We observed histological, ultrastructural, and immunohistochemical changes in the xenografted tumor at different times after implantation. Chemokine ligand expression peaked twice, once during the first 48 hours and again in the second week. We observed that tumor cells in contact with murine peritumoral stroma presented higher expression of chemokine ligands as well as more tumor cells around the capillary vessels. Mouse serum vascular endothelial growth factor levels peaked twice, once in the first hours and then in the second week after tumor implantation. CONCLUSION: Chemokines and other angiogenic factors may be relevant in the angiogenic mechanism during tumor growth. This model provides information on the early stages of the angiogenic process and could be a useful tool in researching anti-angiogenic drugs for new therapeutic strategies in EWS.

High frequency of central memory regulatory T cells allows detection of liver recipients at risk of early acute rejection within the first month after transplantation.

Several studies have analyzed the potential of T regulatory cells (Treg cells) as biomarkers of acute rejection (AR). The aim of the present multicenter study was to correlate the percentage of peripheral Treg cells in liver graft recipients drawn at baseline up to 12 months after transplantation with the presence of AR. The percentage of central memory (cm) Treg cells (CD4(+)CD25(high)CD45RO(+)CD62L(+)) was monitored at pre-transplant and at 1 and 2 weeks, and 1, 2, 3 and 6 months and 1 year post-transplantation. The same validation standard operating procedures were used in all participating centers. Fifteen patients developed AR (23.4%). Hepatitis C virus recurrence was observed in 16 recipients, who displayed low peripheral blood cmTreg levels compared with patients who did not. A steady increase of cmTregs was observed during the first month after transplantation with statistically significant differences between AR and non-AR patients. The high frequency of memory Treg cells allowed us to monitor rejection episodes during the first month post-transplantation. On the basis of these data, we developed a prediction model for assessing risk of AR that can provide clinicians with useful information for managing patients individually and customizing immunosuppressive therapies.

The Role of Immunohistochemistry in Rhabdomyosarcoma Diagnosis Using Tissue Microarray Technology and a Xenograft Model.

Rhabdomyosarcomas (RMS) may resemble other non-myogenic sarcomas and malignant rhabdoid tumor (MRT). Alveolar rhabdomyosarcoma (ARMS) often harbors a typical translocation, but embryonal rhabdomyosarcoma (ERMS) lacks any specific rearrangement. Histopathology is not always sufficient for an unequivocal diagnosis, necessitating ancillary studies, including immunohistochemistry (IHC). Sixteen genetically tested RMS and two MRT were xenografted and followed in successive passages. Tissue microarrays were constructed including samples from original and xenograft tumors. Desmin, myogenin, CK, EMA, INI1, LSD1, AP2ß, fibrillin-2, HMGA2, nestin, and SIRT1 were tested using immunohistochemical staining. Desmin and myogenin were positive in all RMS, and the epithelial markers were negative in almost all RMS. New markers (LSD1, AP2ß, HMGA2, Nestin, and SIRT1) were positive in all RMS and MRT. There were no differences in IHC expression between the three RMS subtypes tested except fibrillin-2, which was negative in ARMS. Applying new IHC markers can contribute to RMS diagnosis. Nevertheless, most markers are also expressed in MRT, and further studies are needed to confirm their value against this and other small round cell tumors.

Metachondromatosis: A Confusing Disease.

Metachondromatosis is a rare autosomal dominant genetic disease with incomplete penetrance that involves abnormal function of the PTPN11 gene. Differentiation between chondrogenic tumors is a challenge for orthopedists. We report a case of a 5 year-old girl with metachondromatosis, a disease that shares attributes with osteochondromas and enchondromas. We found multiple osteochondroma-like lesions with the atypical characteristic of guiding its growth toward the neighboring joint (epyphisis) instead of moving away from it. Furthermore, columnar enchondroma-like lesions were clearly visible in the right distal radius, in the proximal femoral cervix and in the iliac crests. The patient reported that some other tumor had disappeared or downsized with time. This case was debated between a multidisciplinary skeletal dysplasia group. The aforementioned clinical and radiographic findings reinforced the hypothetical diagnosis of metachondromatosis. Definitive diagnosis of metachondromatosis requires a combination of clinical, radiographical and histopathological findings. Differential diagnosis between enchondromas, osteochondromas and metachondromatosis is vital due to differences in malignization and natural history. When a patient has multiple enchondromas and osteochondromas with regression of some lesions and atypical radiographical characteristic of the osteochondroma-like lesions pointing toward the epiphysis, metachondromatosis, a rare disease, must be considered. Surgical treatment is reserved for painful lesions Risk of malignization is insignificant and genetic advice must be given due it is an autosomal dominant disease.

Primary Papillary Colonic Adenocarcinoma With PDGFRA Mutation. A New Morphological Subtype? A Case Report and Review of Literature.

Classic colon carcinomas are defined as adenocarcinomas, characterized by groups of medium/large cells with basophilic and polymorphous nuclei and an eosinophilic elongated cytoplasm, that rearrange on glandular structures. Signs of poor prognosis include high tumor budding, lymphovascular and perineural invasion, poor differentiation, positive margins, and CDX2 loss. Less frequent colon carcinoma subtypes are: mucinous, medullary, signet-ring cell, squamous cell, small cell and undifferentiated carcinoma, among others. In the following case report, we present a 65-year-old woman with a T2N0Mx colon carcinoma with a remarkable papillary and follicular histological appearance. The immunohistochemical stains confirmed an intestinal origin (CDX2+) and excluded a thyroid, gynecological, and urological metastasis, with tumor cells negative for GATA3, PAX8, TTF-1, and thyroglobulin. There was no loss of mismatch repair proteins and p53 showed a wild-type staining. next generation sequencing showed a platelet-derivated growth factor receptor alpha (PDGFRA) mutation. To the best of our knowledge, there have been only two examples of primary papillary colon carcinoma reported in the literature, and neither of them with a PDGFRA mutation. We describe one tumor and discuss its pathological features.

Solitary fibrous tumor: Can the new Huang risk stratification system for orbital tumors improve prognostic accuracy in other tumor locations?

Solitary fibrous tumors (SFTs) are known for their heterogeneous morphology, characterized by a variety of cell shapes and different growth patterns. They can also arise in various anatomical locations, most commonly in extremities and deep soft tissues. Despite this diversity in morphology and location, all SFTs share a common molecular signature involving the NAB2::STAT6 gene fusion. Due to their unpredictable clinical behavior, establishing prognostic factors is crucial. This study aims to evaluate an orbital risk stratification system (RSS) proposed by Huang et al. for use in extraorbital SFTs using a database of 97 cases. The Huang model takes into consideration tumor size, mitotic figures, Ki-67 index, and dominant constituent cell (DCC) as key variables. Survival analysis confirmed the model's predictive value, with higher-risk scores being associated with poorer outcomes. However, in contrast to the orbital SFTs studied by Huang et al., our study did not find a correlation between tumor size and recurrence in extraorbital cases. While the Huang model performs slightly better than other RSS, it falls short on achieving statistical significance in distinguishing recurrence risk groups in extraorbital locations. In conclusion, this study validates the Huang RSS for use in extraorbital SFTs and underscores the importance of considering DCC, mitotic count, and Ki-67 together. However, we found that including tumor size in this model did not improve prognostic significance in extraorbital SFTs. Despite the benefits of this additional RSS, vigilant monitoring remains essential, even in cases classified as low-risk due to the inherent unpredictability of SFT clinical outcomes.

A comparison of whole-mount and conventional sections for pathological mesorectal extension and circumferential resection margin assessment after total mesorectal excision.

INTRODUCTION: The objective of the study is to compare 2 techniques for histological handling of rectal cancer specimens, namely whole-mount in a large block vs conventional sampling using small blocks, for mesorectal pathological assessment of circumferential resection margin status and depth of tumor invasion into the mesorectal fat. METHODS: This is a prospective study including 27 total mesorectal excision specimens of rectal cancer from patients treated for primary rectal carcinoma between 2020 and 2022 in a specialized multidisciplinary Colorectal Unit. For each total mesorectal excision specimen, 2 contiguous representative tumoral slices were selected and comparatively analyzed with whole-mount and small blocks macroscopic dissection techniques, enabling comparison between them in the same surgical specimen. The agreement between the 2 techniques to assess the distance of the tumor from the circumferential resection margin as well as the depth of tumor invasion was evaluated with the Student's t-test for paired samples, Pearson's correlation coefficient, and the Bland-Altman method comparison analysis. RESULTS: Complete mesorectal excision was observed in 8% of cases. Circumferential resection margin involvement was observed in only one case (4 %). The whole-mount and small block techniques obtained similar results when we assessed the distance to the circumferential resection margin (t-test P = 0.8, r = 0.92) and the depth of mesorectal infiltration (t-test P = 0.6, r = 0.95). CONCLUSIONS: Both gross dissection techniques (whole-mount vs multiple small cassettes) are equivalent and reliable to assess the distance to circumferential resection margin and the depth of mesorectal infiltration in the mesorectal fat in rectal cancer staging.

Extraskeletal myxoid chondrosarcoma: p53 and Ki-67 offer prognostic value for clinical outcome - an immunohistochemical and molecular analysis of 31 cases.

Extraskeletal myxoid chondrosarcoma (EMC) is a rare malignant soft tissue tumor of unpredictable clinical behavior. The morphological spectrum of EMC based on histology alone can be difficult. There is no precise immunohistochemical (IHC) profile that together with the clinical parameters is able to predict the clinical outcome. We studied 31 cases confirmed as EMC. Clinical and follow-up data were recorded. Histopathological, molecular, and IHC studies were performed. Association among histopathological parameters was assessed using a chi-square test to determine homogeneity or linear trend for ordinal variables. The Kaplan-Meier proportional risk test (log rank) was used to study the impact of the histological, IHC, and molecular factors on progression-free survival (PFS) and disease-specific survival (DSS). Most EMCs showed a typical architectural pattern. Only a few cases presented an atypical histology (higher cellularity and solid pattern). IHC positivity (focal or diffuse) was present for CDK4 (100%), STAT-6 (90%), CD117 (84%), HNK-1 (81%), SATB2 (68%), and S-100 (58%). Synaptophysin and INSM1 were expressed in 22.6% and 38.7% of cases respectively. The EWSR1::NR4A3 rearrangement was found in 19 cases and 7 tumors presented the TAF15::NR4A3 fusion. Positive surgical margins together with atypical histology and expression of p53 and Ki67 correlated with worse clinical prognosis. EMCs express several IHC markers which are also seen in other soft tissue sarcomas. The molecular detection of NR4A3 rearrangement supports the differential diagnosis. Positive surgical margins together with atypical histology and positive expression of p53 and Ki-67 seem to predict a poor clinical outcome with worse prognosis, increased rate of recurrence, metastasis, and poor overall survival.

The value of GLI1 and p16 immunohistochemistry in the premolecular screening for GLI1-altered mesenchymal neoplasms.

Mesenchymal neoplasms with GLI1 alterations have recently been reported in several anatomic locations. Their morphology and immunohistochemistry (IHC) are nonspecific, making their recognition a true challenge. To assess the diagnostic value of GLI1 and p16 IHC for identifying GLI1-altered neoplasms, we evaluated 12 such neoplasms (6 GLI1-amplified and 6 with GLI1-fusions) using the GLI1 IHC. Additionally, we evaluated some of their morphological and molecular mimickers, including glomangiomas, Ewing sarcomas (ES), myxoid liposarcomas, and MDM2/CDK4-amplified sarcomas (well-differentiated liposarcoma/WDLPS, dedifferentiated liposarcoma/DDLPS, and intimal sarcoma). All successfully tested GLI1-altered tumors (11/11) demonstrated at least moderate/strong nuclear and/or cytoplasmic GLI1 IHC positivity. GLI1-amplified tumors exhibited a moderate/strong predominantly nuclear staining, compared to a moderate, patchy, and predominantly cytoplasmic GLI1 positivity in GLI1-fusion tumors. Among their mimics, GLI1 immunoreactivity, either cytoplasmic or nuclear, was observed in intimal sarcoma (3/3) and WDLPS/DDLPS (22/25). GLI1 IHC demonstrated 92% sensitivity and 90.8% specificity in diagnosing GLI1-altered neoplasms. Strong/moderate nuclear/cytoplasmic p16 immunoexpression was noted in all GLI1-amplified tumors compared to none of fused cases. Overall, the GLI1/p16 combination demonstrated a sensitivity and specificity of 100% and 93% for GLI1-amplified tumors. In conclusion, we confirm that GLI1 IHC represents a good, quick, and cheap helpful screening tool. The inclusion of p16 may aid in pre-screening for potential GLI1-amplified neoplasms and provide insights on which tumors warrant further molecular testing.