Standardized Pathology Report for Colorectal Cancer, 2nd Edition

The first edition of the ‘Standardized Pathology Report for Colorectal Cancer,’ which was developed by the Gastrointestinal Pathology Study Group (GIP) of the Korean Society of Pathologists, was published 13 years ago. Meanwhile, there have been many changes in the pathologic diagnosis of colorectal cancer (CRC), pathologic findings included in the pathology report, and immunohistochemical and molecular pathology required for the diagnosis and treatment of colorectal cancer. In order to reflect these changes, we (GIP) decided to make the second edition of the report. The purpose of this standardized pathology report is to provide a practical protocol for Korean pathologists, which could help diagnose and treat CRC patients. This report consists of “standard data elements” and “conditional data elements.” Basic pathologic findings and parts necessary for prognostication of CRC patients are classified as “standard data elements,” while other prognostic factors and factors related to adjuvant therapy are classified as “conditional data elements” so that each institution could select the contents according to the characteristics of the institution. The Korean version is also provided separately so that Korean pathologists can easily understand and use this report. We hope that this report will be helpful in the daily practice of CRC diagnosis.

Pancreatic High-Grade Neuroendocrine Neoplasms in the Korean Population: A Multicenter Study / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#The most recent 2017 World Health Organization (WHO) classification of pancreatic neuroendocrine neoplasms (PanNENs) has refined the three-tiered 2010 scheme by separating grade 3 pancreatic neuroendocrine tumors (G3 PanNETs) from poorly differentiated pancreatic neuroendocrine carcinomas (PanNECs). However, differentiating between G3 Pan- NETs and PanNECs is difficult in clinical practice. @*Materials and Methods@#Eighty-two surgically resected PanNENs were collected from 16 institutions and reclassified according to the 2017 WHO classification based on the histological features and proliferation index (mitosis and Ki-67). Immunohistochemical stains for ATRX, DAXX, retinoblastoma, p53, Smad4, p16, and MUC1 were performed for 15 high-grade PanNENs. @*Results@#Re-classification resulted in 20 G1 PanNETs (24%), 47 G2 PanNETs (57%), eight G3 well-differentiated PanNETs (10%), and seven poorly differentiated PanNECs (9%). PanNECs showed more frequent diffuse nuclear atypia, solid growth patterns and apoptosis, less frequent organoid growth and regular vascular patterns, and absence of low-grade PanNET components than PanNETs. The Ki-67 index was significantly higher in PanNEC (58.2%± 15.1%) compared to G3 PanNET (22.6%±6.1%, p < 0.001). Abnormal expression of any two of p53, p16, MUC1, and Smad4 could discriminate PanNECs from G3 PanNETs with 100% specificity and 87.5% sensitivity. @*Conclusion@#Histological features supporting the diagnosis of PanNECs over G3 PanNETs were the absence of a low-grade PanNET component in the tumor, the presence of diffuse marked nuclear atypia, solid growth pattern, frequent apoptosis and markedly increased proliferative activity with homogeneous Ki-67 labeling. Immunohistochemical stains for p53, p16, MUC1, and Smad4 may be helpful in distinguishing PanNECs from G3 PanNETs in histologically ambiguous cases, especially in diagnostic practice when only small biopsied tissues are available.

Lymph node micrometastasis in stage I and II rectal cancer

PURPOSE: The aim of this study was to determine the rate of lymph node (LN) micrometastasis in patients with stage I and II rectal cancer.METHODS: One hundred eighty patients with either stage I or II rectal carcinoma who underwent curative resection between 1995 and 2010 were included. Forty-eight patients received neoadjuvant chemoradiotherapy. Two sections from each LN were stained with hematoxylin and eosin (H&E) and with CK20 by immunohistochemistry (IHC), respectively.RESULTS: A total of 2,257 LNs with a median of 12.5 LNs per patient were examined. For IHC staining, CK20-positive neoplastic cells were found in 4 of the 2,257 LNs (0.2%) from 3 of the 180 patients (1.7%), and all corresponding H&E re-stained sections confirmed that these neoplastic cells were present. Three of four neoplastic cells were micrometastasis, and one was macrometastasis. All occult neoplastic cells were found in 3 of the 85 patients (3.5%) with stage II disease.CONCLUSION: We observed a 3.5% rate of occult neoplastic cells in stage II rectal cancer. Interestingly, the results of IHC staining corresponded with those of H&E re-stained sections, suggesting that the examination of H&E stained section by a competent pathologist may replace IHC staining.

Grover Disease Showing Features of Nonspecific Eczematous Dermatosis / 대한피부과학회지

Grover disease (GD), also referred to as transient or persistent acantholytic dermatosis, is an acquired pruritic papular or papulovesicular eruption characterized histopathologically by focal acantholysis and dyskeratosis. Because GD resembles several generalized papular diseases, the diagnosis of GD is a clinical challenge, particularly when dermatologists meet patients without papular eruptions. We experienced two elderly men showing eczematoid plaques with severe pruritus on their backs. Histopathological examinations revealed a focal acantholysis, spongiosis, and dyskeratosis, a pattern consistent with GD. We report two cases of GD with clinical features of nonspecific eczematous dermatosis.

Grover Disease Showing Features of Nonspecific Eczematous Dermatosis / 대한피부과학회지

Grover disease (GD), also referred to as transient or persistent acantholytic dermatosis, is an acquired pruritic papular or papulovesicular eruption characterized histopathologically by focal acantholysis and dyskeratosis. Because GD resembles several generalized papular diseases, the diagnosis of GD is a clinical challenge, particularly when dermatologists meet patients without papular eruptions. We experienced two elderly men showing eczematoid plaques with severe pruritus on their backs. Histopathological examinations revealed a focal acantholysis, spongiosis, and dyskeratosis, a pattern consistent with GD. We report two cases of GD with clinical features of nonspecific eczematous dermatosis.

Epidermoid Cyst of the Cecum

An epidermoid cyst of the cecum is extremely rare; only eight cases have been reported in the literature. A 63-year-old woman was admitted to Kyung Hee University Medical Center with a colonic mass that had been discovered incidentally during a regular health check-up. The radiographic impression was that this mass was a gastrointestinal stromal tumor. During surgery, an exophytic mass in the cecal wall was resected by using an ileocecectomy. Based on the macroscopic and the microscopic findings, this case was identified as an epidermoid cyst of the cecal wall. We report this case to discuss the origin of this entity and the unusual nature of our case.

IDH Mutation Analysis in Ewing Sarcoma Family Tumors

BACKGROUND: Isocitrate dehydrogenase (IDH) catalyzes the oxidative decarboxylation of isocitrate to yield alpha-ketoglutarate (alpha-KG) with production of reduced nicotinamide adenine dinucleotide (NADH). Dysfunctional IDH leads to reduced production of alpha-KG and NADH and increased production of 2-hydroxyglutarate, an oncometabolite. This results in increased oxidative damage and stabilization of hypoxia-inducible factor alpha, causing cells to be prone to tumorigenesis. METHODS: This study investigated IDH mutations in 61 Ewing sarcoma family tumors (ESFTs), using a pentose nucleic acid clamping method and direct sequencing. RESULTS: We identified four cases of ESFTs harboring IDH mutations. The number of IDH1 and IDH2 mutations was equal and the subtype of IDH mutations was variable. Clinicopathologic analysis according to IDH mutation status did not reveal significant results. CONCLUSIONS: This study is the first to report IDH mutations in ESFTs. The results indicate that ESFTs can harbor IDH mutations in previously known hot-spot regions, although their incidence is rare. Further validation with a larger case-based study would establish more reliable and significant data on prevalence rate and the biological significance of IDH mutations in ESFTs.

Recurrent Thyroid Papillary Carcinoma in Children Under Ten Years Old: Report of Two Cases and Literature Review

Papillary thyroid carcinoma (PTC) in children under ten years old is very rare. To date, 18 cases of PTC in children under ten years old (including our two cases) have been reported in Korea. Here, we describe two cases of recurrent PTC with follicular variant and conventional type in an 8-year-old boy and a 7-year-old boy, respectively, and discuss clinicopathologic and molecular characteristics that differ in pediatric patients from adults.

Prevalence of Proximal Serrated Polyps and Conventional Adenomas in an Asymptomatic Average-Risk Screening Population

BACKGROUND/AIMS: Detection of proximal serrated polyps (PSPs) is increasingly recognized as a new qualitative target for colonoscopy. The aims of this study were to assess the detected prevalence of PSPs and synchronous adenomas in an asymptomatic average-risk screening cohort and to evaluate potential factors associated with detection of PSPs. METHODS: The study included 1,375 asymptomatic average-risk Korean patients (aged 50 years or older) who underwent screening colonoscopy. In total, 1,710 polyps were evaluated pathologically. RESULTS: The overall PSP detection rate (PSPDR) was low at 3.1%, despite high polyp (54.0%) and adenoma detection rates (ADRs, 43.5%). ADR did not correlate with PSPDR, but it was strongly correlated with PDR (r=0.810; p<0.001). Patients with PSPs were more likely to have longer withdrawal time and more proximal colon adenomas than patients without PSPs (adjusted odds ratio [OR], 1.19; 95% confidence interval [CI], 1.09 to 1.31; p<0.001) (adjusted OR, 2.03; 95% CI, 1.06 to 3.88; p=0.031, respectively). CONCLUSIONS: The detected prevalence of PSPs was low (<5%) in an asymptomatic average-risk screening Korean population, despite the high prevalence of conventional adenomas. A longer mucosal inspection of the proximal colon may serve as a practical method to enhance detection of PSPs.

A Giant Peritoneal Loose Body

Peritoneal loose bodies (PLBs) are usually discovered incidentally during laparotomy or autopsy. A few cases of giant PLBs presenting with various symptoms have been reported in the literature. Here, we describe a case of a giant PLB incidentally found in the pelvic cavity of a 50-year-old man. Computed tomography revealed a free ovoid mass in the pelvic cavity that consisted of central dense, heterogeneous calcifications and peripheral soft tissue. The mass was an egg-shaped, hard, glistening concretion measuring 7.5x7.0x6.8 cm and weighing 160 g. This concretion consisted of central necrotic fatty tissue surrounded by concentrically laminated, acellular, fibrous material. Small PLBs usually do not require any specific treatment. However, if PLBs cause alimentary or urinary symptoms due to their large size, surgical removal may be recommended. It is essential for clinicians to be aware of this entity and its characteristic features to establish the correct diagnosis.

Proposal for a Standardized Pathology Report of Gastroenteropancreatic Neuroendocrine Tumors: Prognostic Significance of Pathological Parameters

BACKGROUND: There is confusion in the diagnosis and biological behaviors of gastroenteropancreatic neuroendocrine tumors (GEP-NETs), because of independently proposed nomenclatures and classifications. A standardized form of pathology report is required for the proper management of patients. METHODS: We discussed the proper pathological evaluation of GEP-NET at the consensus conference of the subcommittee meeting for the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists. We then verified the prognostic significance of pathological parameters from our previous nationwide collection of pathological data from 28 hospitals in Korea to determine the essential data set for a pathology report. RESULTS: Histological classification, grading (mitosis and/or Ki-67 labeling index), T staging (extent, size), lymph node metastasis, and lymphovascular and perineural invasion were significant prognostic factors and essential for the pathology report of GEP-NET, while immunostaining such as synaptophysin and chromogranin may be optional. Furthermore, the staging system, either that of the 2010 American Joint Cancer Committee (AJCC) or the European Neuroendocrine Tumor Society (ENETS), should be specified, especially for pancreatic neuroendocrine neoplasms. CONCLUSIONS: A standardized pathology report is crucial for the proper management and prediction of prognosis of patients with GEP-NET.

Actinomycotic Brain Abscess Developed 10 Years after Head Trauma

No abstract available.

Papillary Carcinoma of the Thyroid Gland with Nodular Fasciitis-like Stroma

Papillary thyroid carcinoma with nodular fasciitis-like stroma (PTC-NFS) is a rare variant of PTC. The term 'PTC with fibromatosis-like stroma' has been used as a synonym to describe this variant. It is characterized by extensive proliferation of fibroblasts and myofibroblasts in the tumor stroma, which occurs in up to 80% of the tumors. We herein describe a case of PTC-NFS which developed in a 49-year-old woman with the demonstration of findings of ultrasonography, fine needle aspiration cytology and histological examination of the lesion. To characterize the stromal components, we investigated the expression of several immunohistochemical markers which have been shown to be expressed differently in nodular fasciitis (NF) and fibromatosis (FM). The immunostaining results demonstrated nuclear and cytoplasmic accumulation of beta-catenin, cytoplasmic transforming growth factor-beta expression and nuclear Smad expression in the stromal cells, suggesting that the stromal cells in this case have similar molecular profiles to those of FM rather than NF.

Multifocal Renal Cell Carcinoma of Different Histological Subtypes in Autosomal Dominant Polycystic Kidney Disease

Renal cell carcinoma (RCC) in autosomal dominant polycystic kidney (ADPKD) is rare. To date, 54 cases of RCC in ADPKD have been reported. Among these, only 2 cases have different histologic types of RCC. Here we describe a 45-year-old man who received radical nephrectomy for multifocal RCC with synchronous papillary and clear cell histology in ADPKD and chronic renal failure under regular hemodialysis. The case reported herein is another example of the rare pathological finding of RCC arising in a patient with ADPKD.

Multifocal Adenocarcinomas Arising within a Gastric Inverted Hyperplastic Polyp

We present herein the occurrence of multifocal adenocarcinomas with a minute signet ring cell carcinoma that arose within a gastric inverted hyperplastic polyp (IHP) in a 40-year-old woman. Endoscopic ultrasonography demonstrated a heterogeneous hypoechoic mass in the third layer of the gastric wall. The endoscopic submucosal dissection specimen measuring 3.5x3.2x1.8 cm was a well-circumscribed protruding lesion that had a slit-shaped cavity. Histologically, the lesion consisted mainly of endophytic proliferation of hyperplastic columnar cells resembling normal foveolar epithelium. In addition, six foci of adenocarcinomas and a minute focus of signet ring cell carcinoma were randomly distributed in the superficial and deep regions. The adenocarcinoma was gradually transitioning from dysplasia, while the signet ring cell carcinoma was surrounded by hyperplastic foveolar epithelium. This is the first report of a gastric IHP with multifocal intramucosal adenocarcinomas and a signet ring cell carcinoma, and endoscopic submucosal dissection is used to completely resect it.

Current Trends of the Incidence and Pathological Diagnosis of Gastroenteropancreatic Neuroendocrine Tumors (GEP-NETs) in Korea 2000-2009: Multicenter Study / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: As a result of various independently proposed nomenclatures and classifications, there is confusion in the diagnosis and prediction of biological behavior of gastroenteropancreatic neuroendocrine tumors (GEP-NETs). A comprehensive nationwide study is needed in order to understand the biological characteristics of GEP-NETs in Korea. MATERIALS AND METHODS: We collected 4,951 pathology reports from 29 hospitals in Korea between 2000 and 2009. Kaplan-Meier survival analysis was used to determine the prognostic significance of clinicopathological parameters. RESULTS: Although the GEP-NET is a relatively rare tumor in Korea, its incidence has increased during the last decade, with the most significant increase found in the rectum. The 10-year survival rate for well-differentiated endocrine tumor was 92.89%, in contrast to 85.74% in well differentiated neuroendocrine carcinoma and 34.59% in poorly differentiated neuroendocrine carcinoma. Disease related death was most common in the biliary tract (62.2%) and very rare in the rectum (5.2%). In Kaplan-Meier survival analysis, tumor location, histological classification, extent, size, mitosis, Ki-67 labeling index, synaptophysin expression, lymphovascular invasion, perineural invasion, and lymph node metastasis showed prognostic significance (p<0.05), however, chromogranin expression did not (p=0.148). The 2000 and 2010 World Health Organization (WHO) classification proposals were useful for prediction of the prognosis of GEP-NET. CONCLUSION: The incidence of GEP-NET in Korea has shown a remarkable increase during the last decade, however, the distribution of tumors in the digestive system differs from that of western reports. Assessment of pathological parameters, including immunostaining, is crucial in understanding biological behavior of the tumor as well as predicting prognosis of patients with GEP-NET.

Ectopic Epididymis in Testicular Appendices: Report of Two Cases

We report two cases of ectopic epididymal ducts and efferent ductules in the testicular appendices (TAs) of adult men with normally descended testes. In both cases, a sessile TA was incidentally found at the upper pole of the right testis during the scrotal hydrocelectomy. Microscopically, a few closely arranged tubules were detected within the TA. In the first case, the tubules were lined with a pseudostratified columnar epithelium with numerous, long microvilli, and were surrounded by a smooth muscle coat. In contrast, in the second case, the tubules had a wavy luminal surface, because ciliated columnar cells alternated with groups of cuboidal cells. In both cases, strong CD10 immunoreactivity was observed in the luminal border of the lining epithelium. Surgical pathologists should be aware of the presence of both ectopic epididymal ducts and efferent ductules that can occur in TAs, in order to avoid misinterpretation as transected, functional reproductive structures.

14-bp Insertion/Deletion Polymorphism of the HLA-G Gene in Osteosarcoma Patients

BACKGROUND: The major histocompatibility complex class I, G (human leukocyte antigen-G [HLA-G]) gene plays a vital role in the suppression of immune responses. Recently, a number of studies have reported an association between HLA-G and diseases (pregnancy complications, organ transplantation, and tumors). Some of the studies have revealed that the 14-bp insertion/deletion polymorphism might be associated with various diseases. The aim of the present study was to explore a possible influence of the 14-bp insertion/deletion polymorphism on osteosarcoma. METHODS: Genomic DNA was extracted from 75 formalin-fixed, paraffin-embedded tumor tissues derived from patients with conventional osteosarcoma (OSA) and 183 peripheral blood samples of healthy controls. Fifty-eight cases were South Korean patients with OSA and 17 cases were Argentine patients with OSA. The HLA-G 14-bp insertion/deletion polymorphism at exon 8 of the HLA-G locus was analyzed by polymerase chain reaction. RESULTS: There was a significantly different distribution profile for the 14-bp genotypes between the Korean OSA and Korean control groups. Specifically, there were more heterozygote 210 bp/224 bp genotypes in the Korean OSA group when compared to the Korean control group (62.1% vs 40.4%, p=0.002). CONCLUSIONS: The results suggest that HLA-G heterozygote patients may be more susceptible to OSA in the Korean population.

The Global Histone Modification Patterns of Osteosarcoma

BACKGROUND: Epigenetic alteration may affect a patient's prognosis by altering the development and progression of the tumor. Some recent reports have identified a correlation between histone modification and patient outcome. However, no studies have been conducted on global histone modification in osteosarcomas. METHODS: We investigated histone modification in 54 cases of osteosarcoma by performing immunohistochemical staining. The immunohistochemical expression of four histone modification markers, acetylated H4 lysine 12 (H4K12Ac), acetylated H3 lysine 18, trimethylated H3 lysine 27, and dimethylated H3 lysine 4 were evaluated. RESULTS: High H4K12Ac expression was correlated with patient age (p=0.011). However, the other histone modification markers showed no correlation with any of the clinicopathological data such as survival, tumor grade, tumor site, metastasis, age, or gender. CONCLUSIONS: Our study showed that all four histone modification markers are expressed in osteosarcoma (median expression rate, 40 to 60%). However, we did not find a correlation with the clinicopathological factors except for age. Further study to evaluate the reason for the association between H4K12Ac and patient age is needed.

Collision Tumor Composed of a Granulocytic Sarcoma and an Adenocarcinoma of the Stomach: A Case Report

Granulocytic sarcoma, also called chloroma or myeloblastoma, is an extramedullary invasive tumor composed of neoplastic myeloid cells. In this report, we describe a 43-year-old male patient with a collision tumor composed of an adenocarcinoma and a granulocytic sarcoma in the stomach. The coexistence of a granulocytic sarcoma and adenocarcinoma in the stomach has, to the best of our knowledge, not been reported in the literature. The diagnosis of granulocytic sarcoma is very difficult; especially in the absence of concurrent hematologic disease or in the uncommon setting of coexistence with another tumor. Cautious observation is needed when a finding of unusual atypical cells admixed with an adenocarcinoma in the stomach is confronted.