Prognosis of thymic epithelial tumors according to the new World Health Organization histologic classification

Background

The aim of this study was to document the prognosis of thymic epithelial tumors (TETs) according to new the World Health Organization (WHO) classification.

Methods

We retrospectively reviewed 150 patients with TETs that were confirmed pathologically during 11 years (from 1992 to 2002) in Severance Hospital, Seoul, Korea.

Results

TETs were classified as type A, AB, B1, B2, B3, or C, tumors and these represented 7 (4.7%), 26 (17.3%), 13 (8.7%), 45 (30.0%), 26 (17.3%), and 33 (22.0%) cases, and the 5-year survival rates were 100%, 93%, 89%, 82%, 71%, and 23%, respectively. Their Masaoka stages were I, II, III, IVa, and IVb, with 53 (35.3%), 39 (26.0%), 20 (13.3%), 22 (14.7%), and 16 (10.7%) cases. Tumor invasiveness, recurrence, completeness of resection, and tumor-related death were more frequent in types AB, B2, B3, and C than in types A and B1. Multivariate analysis showed that Masaoka stage (p < 0.001) and the WHO classification (p = 0.019) were significant independent prognostic factors.

Conclusions

The WHO classification is associated with tumor invasiveness, recurrence, completeness of resection, and tumor-related death, and has good correlation with Masaoka stage. The WHO histologic subtypes are an independently significant prognostic factor with respect to survival in our multivariate analysis. Types AB, B2, B3, and C showed invasive behaviors and R1 or R2 resections were frequently performed. Postoperative adjuvant radiotherapy was effective, but long-term follow-up is recommended because of decreased survival after 5 years following operation. The WHO classification may be helpful in clinical practice for the assessment and treatment of TET patients.     

Histologic typing of thymoma according to the new World Health Organization classification.

The new WHO classification scheme provides a set of simple and easily reproducible morphologic criteria for an accurate and consistent categorization of thymic epithelial tumors. This scheme should facilitate interobserver reproducibility and lead to a more precise assessment of prognosis when used in combination with the staging system.     

New Italian guidelines on bladder cancer,based on the World Health Organization 2004 classification

OBJECTIVE

To provide evidence‐based recommendations on bladder cancer management

METHODS

A multidisciplinary guideline panel composed of urologists, medical oncologists, radiotherapists, general practitioners, radiologists, epidemiologists and methodologists conducted a structured review of previous reports, searching the Medline database from 1 January 2004 to 31 December 2008. The milestone papers published before January 2004 were accepted for analysis. The level of evidence and the grade of the recommendations were established using the GRADE system.

RESULTS

In all, 15 806 references were identified, 1940 retrieved, 1712 eliminated (specifying the reason for their elimination) and 971 included in the analysis, as well as 241 milestone reports. A consensus conference held to discuss the discrepancies between the scientific evidence and the clinical practice was then attended by 122 delegates of various specialities.

CONCLUSION

Recommendations on bladder cancer management are provided.     

Updates of pancreatic neuroendocrine neoplasm in the 2017 World Health Organization classification

The new 2017 World Health Organization (WHO) classification of pancreatic neuroendocrine neoplasms (PanNEN) modifies the previous 2010 version with new grading and staging systems to provide a better prognostic stratification and therapeutic guidance. The discovery of heterogeneity in WHO 2010 G3 category leads to the introduction of the new ‘well‐differentiated neuroendocrine tumor G3’ entity, which is distinct from the poorly‐differentiated pancreatic neuroendocrine carcinoma (PanNEC). The latest findings from molecular studies of PanNEN allow us to have a better understanding of respective biology of PanNET and PanNEC. This review aims at highlighting refinements in the 2017 classification and discusses some of the molecular updates in PanNEN.     

Diagnostic reproducibility of thymic epithelial tumors using the World Health Organization classification: note for thoracic clinicians

Objective

Histopathological diagnosis of thymic epithelial tumors according to the current World Health Organization classification is not adequately reproducible; however, most thoracic clinicians are unaware of this. We illustrate this problem in practical settings to raise clinician awareness.

Methods

An expert pathologist specialized in thymic pathology and a trained general pathologist independently diagnosed 158 resected thymic epithelial tumors. Assuming that the expert’s diagnoses were more accurate, the two pathologists’ diagnoses were judged to be concordant when tumor subtypes (thymoma) or categories (thymic carcinoma and neuroendocrine tumor) were in agreement.

Results

The concordance rates for different thymoma subtypes were 75 % (3/4), 30 % (11/37), 100 % (17/17), 80 % (39/49), and 53 % (9/17) for types A, AB, B1, B2, and B3, respectively. Discordant cases of type AB thymoma were mainly diagnosed as type B1 or B2 by the general pathologist. Discordant cases of type B2 thymoma were diagnosed as type AB, B1, or B3, and discordant cases of type B3 thymoma were diagnosed as type A, B2, or carcinoma. Discordant cases of thymic carcinoma were diagnosed as type A or B3 thymoma.

Conclusion

Investigation of the concordant and discordant cases suggested that reasonable discrepancies can occur because of the noncommittal categorical boundaries inherent in this classification. Thoracic clinicians should consider this potential problem in daily practice.     

Clinical and functional aspects of the World Health Organization histologic classification of thymic epithelial tumors

The World Health Organization (WHO) histologic classification was presented by the international committee to provide a universal system for clinicians and researchers in 1999 and was further modified in 2004. This classification is mainly based on Müller-Hermelink et al.'s system and six distinct types were defined. Thymomas were classified into type A, AB, B1, B2, and B3 tumors, according to the shape and atypia of epithelial cells and also the abundance of lymphocytes. Another type of tumor is thymic carcinomas, which have apparent atypia of neoplastic cells. Neuroendocrine tumor (carcinoid) of the thymus was categorized as thymic carcinoma because of the resemblance of genetic aberrations. Several studies have shown that the WHO histologic type is correlated with the proportion of invasive tumors and is an independent prognostic factor along with Masaoka stage. Furthermore, association with myasthenia gravis, ability to induce CD4+CD8+T cells and express HLA-DR molecules, and chromosomal imbalances such as loss of heterogeneity were found to be correlated with the WHO histologic type. Thus, the WHO histologic classification system reflects the oncologic, immunologic, and genetic characteristics of thymic epithelial tumors. The clinical application of this classification system is expected.     

Effect of varicocele on semen characteristics according to the new 2010 World Health Organization criteria: a systematic review and meta-analysis

This study investigated the effects of varicocele on semen parameters in infertile men based on the new 2010 World Health Organization laboratory manual for the examination of human semen. Semen analysis results (volume, sperm count, motility, and morphology) were the primary outcomes. An electronic search to collect the data was conducted using the Medline/PubMed, SJU discover, and Google Scholar databases. We searched articles published from 2010 to August 2015, i.e., after the publication of the 2010 WHO manual. We included only those studies that reported the actual semen parameters of adult infertile men diagnosed with clinical varicocele and contained a control group of either fertile men or normozoospermic men who were not diagnosed with varicocele. Ten studies were included in the meta-analysis, involving 1232 men. Varicocele was associated with reduced sperm count (mean difference: −44.48 × 10⁶ ml⁻¹; 95% CI: −61.45, −27.51 × 10⁶ ml⁻¹; P < 0.001), motility (mean difference: −26.67%; 95% CI: −34.27, −19.08; P < 0.001), and morphology (mean difference: −19.68%; 95% CI: −29.28, −10.07; P < 0.001) but not semen volume (mean difference: −0.23 ml; 95% CI: −0.64, 0.17). Subgroup analyses indicated that the magnitude of effect was influenced by control subtype but not WHO laboratory manual edition used for semen assessment. We conclude that varicocele is a significant risk factor that negatively affects semen quality, but the observed pooled effect size on semen parameters does not seem to be affected by the WHO laboratory manual edition. Given most of the studies published after 2010 still utilized the 1999 manual for semen analysis, further research is required to fully understand the clinical implication of the 2010 WHO laboratory manual on the association between varicocele and semen parameters.     

Post-resection prognosis of combined hepatocellular carcinoma-cholangiocarcinoma cannot be predicted by the 2019 World Health Organization classification

BackgroundCombined hepatocellular carcinoma and cholangiocarcinoma (cHCC-CCA) has wide histologic diversity. This study investigated the prognostic impacts of cHCC-CCA histology according to the 2019 World Health Organization (WHO) classification.MethodsThis retrospective observational study included 153 patients who underwent surgical resection for cHCC-CCA at Asan Medical Center between August 2012 and July 2019.ResultsDuring the study period, 153 patients, 112 (73.2%) men and 41 (26.8%) women with a mean age of 56.4 ± 10.8 years, underwent R0 resection for cHCC-CCA. Mean tumor diameter was 4.2 ± 2.6 cm, and 147 (96.1%) patients had solitary tumors. According to 2019 WHO classification, 111 (72.5%) patients had cHCC-CCA alone, and 29 of them (26.1%) showed stem cell features. cHCC-CCA-intermediate cell carcinoma and cHCC-CCA-cholangiolocellular carcinoma were identified in 27 (17.6%) and 15 (9.8%), respectively. The 1-, 3-, and 5-year tumor recurrence and patient survival rates were 31.8% and 92.1%, 49.8% and 70.9%, and 59.0% and 61.7%, respectively. Univariate analyses revealed that significant prognostic factors were tumor size >5 cm, microscopic and macroscopic vascular invasion, lymph node metastasis, 8th American Joint Committee on Cancer (AJCC) tumor stage, and status of stem cell features. Multivariate analysis revealed 8th AJCC tumor stage and status of stem cell features as independent prognostic factors. 2019 WHO classification was not associated with post-resection prognosis.Conclusions2019 WHO classification was not associated with post-resection prognosis, thus was considered as simplified histologic classification requiring prognostic validation. We suggest that stem cell features should be included as an essential component of the pathology report for cHCC-CCA.     

Oral non-Hodgkin's lymphoma: review of the literature and World Health Organization classification with reference to 40 cases.

Forty cases of oral cavity non-Hodgkin's lymphoma (NHL) were evaluated for sex, age, location, clinical presentation, and World Health Organization (WHO) histological subtype. Fifty-three percent were female and the mean age was 71. The upper jaw (maxilla or palatal bone), mandible, palatal soft tissue, and vestibule and gingivae (maxillary or mandibular soft tissue involvement only) were, respectively, the most common locations. Swelling, ulceration, and radiographic destruction of bone were the most frequent signs. Most of the lymphomas were of B cell lineage (98%), and the majority of these B cell lymphomas (58%) were histologically subtyped as diffuse large B cell lymphoma, which is considered to have an aggressive clinical course. An immunohistochemical panel was used in the majority of cases to confirm the lineage and to help characterize the subtype. B and T cell specific markers were used to show lineage of the neoplastic cells. Additional markers were used to help confirm specific subtypes that characteristically show specific positivity to some of these antibodies. Molecular studies to detect monoclonal immunoglobulin heavy chain (IgH) gene rearrangements and Bcl-1 and Bcl-2 gene translocations were performed in cases in which the diagnosis was in question. The current WHO classification is also reviewed in detail.     

Neuroendocrine neoplasms of the breast: A review focused on the updated World Health Organization (WHO) 5th Edition morphologic classification

Neuroendocrine breast neoplasms are uncommon invasive carcinomas that have historically been poorly defined due to various definitions of what constitutes a neuroendocrine carcinoma. The 5th Edition of the World Health Organization (WHO) Classification of Breast Tumors has moved to a dichotomous classification of neuroendocrine neoplasms in the breast in order to become standardized with classifications of other organ systems. Neuroendocrine breast neoplasms in the new edition are classified as “neuroendocrine tumor” and “neuroendocrine carcinoma.” Key changes are exclusion of special histologic types (solid papillary carcinoma and hypercellular variant of mucinous carcinoma) and the inclusion of large cell neuroendocrine carcinoma. Neuroendocrine tumors are genetically heterogenous and harbor molecular alterations that differ from invasive carcinoma, no special type. Neuroendocrine carcinomas (high‐grade) show some overlapping molecular alterations with their counterparts in other organ systems. Data regarding the prognostic significance of neuroendocrine differentiation are conflicting, and histologic grade and tumor stage remain the main prognostic parameters. Current management of neuroendocrine neoplasms is not different from other types of breast carcinoma. This review will provide an update to the current WHO classification of neuroendocrine breast neoplasms and describe pertinent clinical, histologic, and molecular features of these uncommon tumors.     

World Health Organization experience in the treatment of melanoma

The method of randomized trials, as performed by the WHO Melanoma Program, has definitely been a legitimate clinical study design in patients with melanoma from about 1970 to the end of the last century. Three important results of these WHO trials have substantially influenced the approach of the clinician towards melanoma: (1) There is no role for elective regional lymph node dissection, (2) narrow local excision of the primary melanoma does not entail additional risks, and (3) adjuvant treatment with chemotherapy or immunotherapy after radical surgery for regional lymph node metastases has not, until now, shown any substantial benefit. A problem arises because randomized clinical studies require long periods of time for patients accrual and completion. Frequently their legitimacy is challenged due to the appearance of new parameters, both regarding staging (eg, the introduction of new technical method such as sentinel node biopsy) and prognosis. Therefore, it would be better to define different clinical study models to quickly test a hypothesis on a small group of selected patients in order to provide quick results. We believe that this is the future of clinical research in the new millennium, because it does not seem reasonable today to plan large clinical trials that need 10 years or more of accrual and follow-up without reaching definite conclusions.     

Necrotising fasciitis: a new management algorithm based on clinical classification

Necrotising fasciitis is a rare infection of the subcutaneous tissues. If untreated, it is invariably fatal, and thus a high index of suspicion for the diagnosis is required. The disease's manifestation can range from a fulminant presentation to a subtle and insidious development. The priority in every case is to proceed to radical surgical debridement. On review of the literature and based on our clinical experience, we propose a new classification based on clinical presentation and suggest an algorithm to facilitate the management of this devastating condition. Increasing awareness should be given to the management of the large wounds resulting from the surgical debridement of necrotising fasciitis.     

Myofibrosarcoma: a clinicopathologic study

The concept of soft tissue sarcomas composed predominantly of myofibroblasts has been controversial. We examined a series of such lesions of low- and intermediate-grade malignancy to further define their clinical and pathologic features. Histologic appearances of four cases diagnosed as myofibrosarcoma by electron microscopy were reviewed. Eleven additional cases with similar morphology were then identified from 249 tumors originally indexed as fibrosarcoma. Electron microscopy was performed on five of these, and immunohistochemistry was carried out on all cases for which material was available. There were 11 men and 4 women aged 33 to 73 years (median, 54 yrs; mean, 53 yrs). Lesions mainly involved the head and neck, extremities, and trunk and ranged in size from 1.5 to 12 cm. The tumors were composed of bland or pleomorphic stellate to spindled cells with eosinophilic cytoplasm and tapered nuclei in a collagenous stroma; 10 were grade 1 and five were grade 2. All sarcomas displayed fascicular or storiform patterns, and some of the grade 1 lesions superficially mimicked nodular fasciitis. Electron microscopy of nine cases showed myofibroblastic differentiation, and immunohistochemistry showed smooth muscle actin in 13 of 15 cases, muscle-specific actin in 7 of 9, desmin in 6 of 14, and cytokeratin in 0 of 11. Four of nine grade 1 and three of four grade 2 tumors recurred (one twice), and one grade 2 tumor metastasized to the lungs. Myofibrosarcomas are indolent low-grade or occasionally aggressive intermediate-grade sarcomas which can be recognized by light microscopy. Their clinical importance lies in the resemblance, particularly of low-grade examples, to reactive or pseudosarcomatous conditions.