Implementing structured pathology reporting protocol for non-melanocytic skin cancers: practical considerations.

Non-melanocytic skin cancers (NMSCs) account for five times the incidence of all other cancers combined and cost US $6 billion annually. These are the most frequent specimens encountered in community pathology practice in many Western countries. Lack of standardised structured pathology reporting protocols (SPRPs) can result in omission of critical information or miscommunication leading to suboptimal patient management. The lack of standardised data has significant downstream public health implications, including insufficient data for reliable development of prognostic tools and health-economy planning. The Royal College of Pathologists of Australasia has developed an NMSC SPRP. A multidisciplinary expert committee including pathologists, surgeons, dermatologists, and radiation and medical oncologists from high volume cancer centres was convened. A systematic literature review was performed to identify evidence for including elements as mandatory standards or best practice guidelines. The SPRP and accompanying commentary of evidence, definitions and criteria was peer reviewed by external stakeholders. Finally, the protocol was revised following feedback and trialled in multiple centres prior to implementation. Some parameters utilised clinically for determining management and prognosis including tumour depth, lymphovascular invasion or distance to the margins lack high level evidence in NMSC. Dermatologists, surgeons, and radiation oncologists welcomed the SPRP. Pathologists indicated that the variety of NMSC specimens ranging from curettes to radical resections as well as significant differences in the biological behaviour of different tumours covered by the NMSC umbrella made use of a single protocol difficult. The feedback included that using a SPRP for low risk NMSC was neither clinically justified nor compensated adequately by the Australian Medicare Reimbursement Schedule. Following stakeholder feedback, the SPRP implementation was restricted to excision specimens of head and neck NMSC; and low-risk NMSC, such as superficial basal cell carcinoma, were excluded. Implementing NMSC SPRP fulfils an unmet clinical need. Unlike other cancers, NMSCs generate a range of specimen types and are reported in a wide range of pathology practices. Limiting use of SPRP to NMSC at higher risk of progression and providing formatted templates for easy incorporation into laboratory information systems were essential to successful deployment. In the future, further consideration should be given to implementing the SPRP to include all relevant specimens, including non-head and neck and low-risk NMSC specimens.

Adjuvant Radiotherapy in Surgically Treated HPV-Positive Oropharyngeal Carcinoma with Adverse Pathological Features.

Purpose: HPV-positive oropharyngeal carcinoma (HPV-OPC) is increasingly treated with primary surgery. The National Comprehensive Cancer Network (NCCN) recommends adjuvant therapy for surgically treated HPV-OPC displaying adverse pathological features (AF). We evaluated adjuvant radiotherapy patterns and outcomes in surgically treated AF-positive HPV-OPC (AF-HPV-OPC). Methods: The National Cancer Database was interrogated for patients ≥ 18 years with early-stage HPV-OPC from 2010 to 2017 who underwent definitive resection. Patients that had an NCCN-defined AF indication for adjuvant radiotherapy were assessed, including positive surgical margins (PSM), extranodal extension (ENE), lymphovascular invasion, and level 4/5 cervical lymph nodes. Overall survival (OS) was evaluated using Cox proportional hazards models and Kaplan−Meier analysis in whole and propensity score matched (PM) cohorts. Results: Of 15,036 patients meeting inclusion criteria, 55.7% were positive for at least one AF. Presence of any AF was associated with worse OS (hazard ratio (HR) = 1.56, p < 0.001). In isolation, each AF was associated with worse OS. On PM analysis, insurance status, T2 category, Charlson-Deyo comorbidity score, ENE (HR = 1.81, p < 0.001), and PSM (HR = 1.58, p = 0.002) were associated with worse OS. Median 3-year OS was 92.0% among AF-HPV-OPC patients undergoing adjuvant radiotherapy and 84.2% for those who did not receive adjuvant radiotherapy (p < 0.001, n = 1678). The overall rate of patients with AF-HPV-OPC who did not receive adjuvant radiotherapy was 13% and increased from 10% in 2010 to 17% in 2017 (ptrend = 0.007). Conclusions: In patients with AF-HPV-OPC, adjuvant radiotherapy is associated with improved survival. In the era of de-escalation therapy for HPV-OPC, our findings demonstrate the persistent prognostic benefit of post-operative radiotherapy in the setting of commonly identified adverse features. Ongoing clinical trials will better elucidate optimized patient selection for de-escalated therapy.

KCNQ1 and lymphovascular invasion are key features in a prognostic classifier for stage II and III colon cancer.

BACKGROUND: The risk of recurrence after resection of a stage II or III colon cancer, and therefore qualification for adjuvant chemotherapy (ACT), is traditionally based on clinicopathological parameters. However, the parameters used in clinical practice are not able to accurately identify all patients with or without minimal residual disease. Some patients considered 'low-risk' do develop recurrence (undertreatment), whilst other patients receiving ACT might not have developed recurrence at all (overtreatment). We previously analysed tumour tissue expression of 28 protein biomarkers that might improve identification of patients at risk of recurrence. In the present study we aimed to build a prognostic classifier based on these 28 biomarkers and clinicopathological parameters. METHODS: Classification and regression tree (CART) analysis was used to build a prognostic classifier based on a well described cohort of 386 patients with stage II and III colon cancer. Separate classifiers were built for patients who were or were not treated with ACT. Routine clinicopathological parameters and tumour tissue immunohistochemistry data were included, available for 28 proteins previously published. Classification trees were pruned until lowest misclassification error was obtained. Survival of the identified subgroups was analysed, and robustness of the selected CART variables was assessed by random forest analysis (1000 trees). RESULTS: In patients not treated with ACT, prognosis was estimated best based on expression of KCNQ1. Poor disease-free survival (DFS) was observed in those with loss of expression of KCNQ1 (HR = 3.38 (95% CI 2.12 - 5.40); p < 0.001). In patients treated with ACT, key prognostic factors were lymphovascular invasion (LVI) and expression of KCNQ1. Patients with LVI showed poorest DFS, whilst patients without LVI and high expression of KCNQ1 showed most favourable survival (HR = 7.50 (95% CI 3.57-15.74); p < 0.001). Patients without LVI and loss of expression of KCNQ1 had intermediate survival (HR = 3.91 (95% CI 1.76 - 8.72); p = 0.001). CONCLUSION: KCNQ1 and LVI were identified as key features in prognostic classifiers for disease-free survival in stage II and III colon cancer patients.

Critical Prognostic Parameters in the Anatomic Pathology Reporting of Differentiated Follicular Cell-Derived Thyroid Carcinoma.

In the past decades, pathology reporting on thyroid carcinoma has evolved from a narrative approach to structured synoptic reports. Many histologic variables are present in the current synoptic reports that are crucial elements for initial risk stratification and clinical management. In this review, we compare and summarize the key prognostic pathologic characteristics utilized by the most influential clinical and pathologic guidelines from the American Thyroid Association (ATA), the National Comprehensive Cancer Network (NCCN), the current World Health Organization (WHO) classification of endocrine tumors (fourth edition), the current American Joint Committee on Cancer (AJCC) staging system (eighth edition), the College of American Pathologists (CAP) protocol, and the International Collaboration on Cancer Reporting (ICCR) dataset. The aim is to provide a comprehensive review focused on the definitions and prognostic impacts of these crucial pathologic parameters.

Clinical impact of ulceration width, lymphovascular invasion, microscopic satellitosis, perineural invasion, and mitotic rate in patients undergoing sentinel lymph node biopsy for cutaneous melanoma: a retrospective observational study at a comprehensive cancer center.

The prognostic significance of the width of the ulceration in primary melanomas remains unclear, and there is a relative paucity of data for lymphovascular invasion (LVI), microscopic satellitosis (MS), perineural invasion (PNI), and mitotic rate when compared with other pathological elements currently required for reporting. To evaluate the prognostic importance of the ulceration width and other important pathologic measurements, a single-institutional retrospective study was conducted using records of cutaneous melanoma patients who underwent sentinel lymph node (SLN) biopsy at The University of Texas, MD Anderson Cancer Center between 2003 and 2008. We identified 1898 eligible patients with median tumor thickness of 1.25 mm and median follow-up of 6.7 years. By multivariable analyses, the strongest risk factor for SLN positivity was high tumor thickness followed by the presence of LVI. The pathologic measures with the strongest influence on recurrence-free survival (RFS) were tumor thickness and positive SLN status. Ulceration width and presence of MS were also significantly associated with RFS while PNI was not. Factors with the strongest influence on melanoma-specific survival (MSS) were positive SLN status and mitotic rate. In conclusion, SLN biopsy should probably be offered if the primary tumor has LVI. MS is an adverse prognostic factor for RFS, but its influence on outcome is modest. Ulceration width predicts RFS but loses its independent prognostic significance for MSS when adjusting for currently used clinicopathological factors. In view of its impact on MSS, mitotic rate should be recorded for cutaneous invasive melanomas across all T categories.

Crucial parameters in thyroid carcinoma reporting - challenges, controversies and clinical implications.

In the modern era, a pathology report of thyroid carcinoma requires the inclusion of numerous prognostically relevant histopathological features, e.g. the presence and extent of vascular and capsular invasion, extrathyroidal extension, the surgical margin status and the characteristics of nodal metastasis. These pathological features are crucial components of the initial risk stratification to determine the need for completion thyroidectomy and/or postoperative radioactive iodine ablation therapy. The current review aims to summarise the diagnostic criteria, the controversies, the prognostic impacts and the challenges of these pathological characteristics, focusing specifically on the parameters that are incorporated into the American Joint Committee on Cancer (AJCC) staging system, the College of American Pathologists (CAP) reporting template, the American Thyroid Association (ATA) and the National Comprehensive Cancer Network (NCCN) guidelines.

Association of lymphovascular invasion with metastasis (loco-regional lymph node or distant) among adult Filipino patients with papillary thyroid carcinoma: A case control study

Background/Objective@#Papillary thyroid carcinoma is the most common type of thyroid cancer. Treatment includes surgery and remnant ablation with radioactive iodine theraphy while follow-up monitoring includes I- 131 whole body scans land thyroglobulin monitoring. Lymphovascular invasion (LVI) has been used as a predictor of metastasis in different cancers. Therefore, it might be useful in predicting metastasis in patients with papillary thyroid carcinoma since metastasis in this type of carcinoma travels via the lymphatic route. The purpose of this study was to determine the association of LVI with metastasis among patients with papillary thyroid carcinoma@*Methodology@#Records of patients with papillary thyroid carcinoma (histopathologic reports, thyroglobulin levevls and I-131 whole body scans) were reviewed. Univariate and multivariate anlyses were performed. @*Results@#A total of 108 subjects were recruited for this study, 47 (43.5%) of which had LVI. There was no association found between LVI and metastasis on baseline (p=0.72) and follow-up scans (p=0.07). However, there was an association between metastasis resolution on follow-up scans and high-dose radioactive treatment (p=0.02) regarless of presence or absence of LVI.@*Conclusion@#There was a significant association of the presence of LVI with elevated thyroglobulin levels (p-value<0.0001). A significant association was also seen with LVI and dose of activity with resolution of thyroid remnant, locoregional lymph node and distant metastasis (p=0.02). Even though no association jwas seen between LVI and metastasis, a robust percentage of patients with LVI were positive for metastasis on whole body scans.

Lymphovascular invasion is associated with survival for papillary thyroid cancer.

Data are limited regarding the association between tumor lymphovascular invasion and survival for patients with papillary thyroid cancer (PTC). This study sought to examine lymphovascular invasion as an independent prognostic factor for patients with PTC undergoing thyroid resection. The National Cancer Data Base (2010-2011) was queried for patients with PTC who underwent total thyroidectomy or lobectomy. Patients were classified into two groups based on the presence/absence of lymphovascular invasion. Demographic, clinical and pathological features were evaluated for all patients. A Cox proportional hazards model was utilized to identify factors associated with survival. Results show that 45,415 patients met inclusion criteria; 11.6% had lymphovascular invasion. Patients with lymphovascular invasion were more likely to have larger tumors (2.8cm vs 1.5cm, P<0.01), metastatic lymph nodes (74.1% vs 32.5%, P<0.01), and distant metastases (3.0% vs 0.5%, P<0.01). They were also more likely to receive radioactive iodine (69.3% vs 44.9%, P<0.01). Unadjusted overall 5-year survival was lower for patients who had tumors with lymphovascular invasion (86.6% vs 94.5%) (log-rank P<0.01). After adjustment, increasing patient age (HR=1.06, P<0.01), male gender (HR=1.68, P<0.01), presence of metastatic lymph nodes (HR=1.77, P<0.01), distant metastases (HR=3.49, P<0.01), and lymphovascular invasion (HR=1.88, P<0.01) were associated with compromised survival. For patients with lymphovascular invasion, treatment with RAI was associated with reduced mortality (HR=0.43, P<0.01). The presence of lymphovascular invasion among patients with PTC is independently associated with compromised survival. Patients who have PTC with lymphovascular invasion should be considered higher risk, and adjuvant RAI should be more strongly considered.

Prognostic significance of the concomitant existence of lymphovascular and perineural invasion in locally advanced gastric cancer patients who underwent curative gastrectomy and adjuvant chemotherapy.

OBJECTIVE: In this study, we evaluated the prognostic significance of the concomitant existence of lymphovascular invasion and perineural invasion in patients with advanced gastric cancer. METHODS: A total of 206 consecutive patients with Stage II or III gastric cancer who underwent curative D2 gastrectomy and adjuvant chemotherapy from April 2004 to December 2011 were analyzed. Patients were classified into four groups according to the presence (+) or absence (-) of lymphovascular invasion and perineural invasion: lymphovascular invasion-/perineural invasion- (n = 33), lymphovascular invasion+/perineural invasion- (n = 31), lymphovascular invasion-/perineural invasion+ (n = 54) and lymphovascular invasion+/perineural invasion+ (n = 88). RESULTS: A total of 136 patients (66.0%) received 5-fluorouracil plus cisplatin adjuvant chemotherapy and 70 patients (34.0%) received TS-1. During the median follow-up period of 35.18 months, the median disease-free survival times for lymphovascular invasion-/perineural invasion-, lymphovascular invasion+/perineural invasion- and lymphovascular invasion-/perineural invasion+ were not reached at the time of analysis; however, median disease-free survival for lymphovascular invasion+/perineural invasion+ was the worst (36.73 months, P = 0.001). The median overall survival in the four groups was also not reached at the time of analysis; however, median overall survival with lymphovascular invasion+/perineural invasion+ was the poorest (P = 0.002). In a multivariate analysis, lymphovascular invasion+/perineural invasion+ was an independent prognostic factor for both disease-free survival (hazard ratio = 1.940, 95% confidence interval 1.157-3.252, P = 0.012) and overall survival (hazard ratio = 2.973, 95% confidence interval 1.561-5.662, P = 0.001). CONCLUSIONS: The concomitant existence of lymphovascular and perineural invasion has a significant prognostic impact on disease-free survival and overall survival in patients with Stage II or III gastric cancer.

Reporting trends and prognostic significance of lymphovascular invasion in muscle-invasive urothelial carcinoma: a population-based study.

OBJECTIVES: To investigate reporting patterns and outcomes associated with lymphovascular invasion in a general population setting. METHODS: We identified all cystectomy patients with muscle-invasive urothelial cancer in Ontario, Canada, 1994-2008. Surgical pathology reports were analyzed for pathological variables including lymphovascular invasion. Lymphovascular invasion reporting patterns were described over time. A Cox proportional hazards model was used to evaluate the association of lymphovascular invasion with survival. RESULTS: Of the 2802 cases identified, lymphovascular invasion status was reported in 75%. Lymphovascular invasion reporting significantly improved over the study period and was correlated with poor prognostic pathological features (T stage and N stage). Comprehensive cancer center status was not consistently associated with lymphovascular invasion reporting. Patients with lymphovascular invasion had substantially lower survival than patients who were lymphovascular invasion-negative or whose lymphovascular invasion status was unstated (P < 0.001). Lymphovascular invasion was independently associated with survival in patients regardless of lymph node metastasis. After adjusting for age, stage, comorbidity, margin status and adjuvant chemotherapy, lymphovascular invasion remained strongly associated with reduced survival (hazard ratio 1.98, 95% confidence interval 1.71-2.29). CONCLUSIONS: Although routine reporting of lymphovascular invasion has improved over the years, pathologists appear to be biased towards evaluating lymphovascular invasion in patients with high-stage disease. Despite this bias, lymphovascular invasion remains an important prognostic factor among patients treated by cystectomy. Pathologists in general practice should report lymphovascular invasion status more consistently and urologists should hold their pathology colleagues to a higher standard.