High-grade Atypia Research Articles

Promoter Hypermethylation of Hallmark Cancer Genes in Atypical Adenomatous Hyperplasia of the Lung

According to current models of tumorigenesis, the progression of phenotypic changes culminating in overtly malignant carcinoma is driven by genetic and epigenetic alterations. The recognition of an early form of glandular neoplasia termed atypical adenomatous hyperplasia (AAH), a precursor lesion from which lung adenocarcinomas arise, provides an opportunity for characterizing early epigenetic alterations involved in lung tumorigenesis. We evaluated AAHs, adjacent normal lung tissue, and synchronous lung adenocarcinomas for promoter hypermethylation of genes implicated in lung tumorigenesis (p16, TIMP3, DAPK, MGMT, RARbeta, RASSF1A, and hTERT). For individual genes and the number of genes methylated, we observed a significant increase in the frequency of promoter hypermethylation in the histologic progression from normal to AAH, with low-grade or high-grade atypia, and finally to adenocarcinoma (P(trend) </= 0.01). Multifocal AAHs from individual patients had distinct patterns of promoter hypermethylation, suggesting divergent epigenetic field defects. There were statistically significant positive associations for the presence of promoter hypermethylation of individual and multiple genes with advanced histology, with odds ratios between 4.3 and 58.5. p16 conveyed the strongest individual association for promoter hypermethylation when comparing tumor or high-grade AAH to low-grade AAH or normal tissue, with an odds ratio of 45.5 (95% confidence interval, 5.8-360.5). This study shows epigenetic progression in the earliest stages of glandular neoplasia of the lung and has implications for early lung cancer detection.

Immunohistochemical Expression of p53 and Ki67 in Colorectal Adenomas and Prediction of Malignancy and Development of New Polyps

The aim of this study was to investigate the immunohistochemical expression of p53 and Ki67 in colorectal adenomas in order to clarify their significance as indicators of malignancy and development of new polyps. Seventy-eight polyps were removed from 51 patients and examined. Twenty-nine patients (56.9%) had adenomas with low-grade atypia (13 of them developed new polyps at 3-year follow-up) and 22 (43.1%) had adenomas with high-grade atypia (6 of them developed new polyps at 3-year follow-up). We tested the association between p53 and Ki67 expression and various clinicopathological variables, and regression analysis was performed to identify the risk factors for malignancy and development of new adenomas. A significant correlation between the grade of atypia and p53 immunoreactivity was observed. Ki67 expression was not related to atypia and no correlation was found between p53 and Ki67 immunoreactivity. Regression analysis showed that size (p=0.0002) and p53 staining (p=0.0111) were the selected factors related to malignant transformation, whereas the number of synchronous primary polyps emerged as the only predictive factor of development of new adenomas, although without statistical significance. The expression of biological markers may be in future added to the currently examined features of polyps; however, further studies are needed to better define their predictive value.

Ovarian Clear Cell Carcinoma With Papillary Features: A Potential Mimic of Serous Tumor of Low Malignant Potential

The differential diagnostic problems usually associated with clear cell carcinoma (CCC) of the ovary have been well characterized and include primitive germ cell tumor, sex cord stromal tumor, and metastasis. Distinction from other types of surface epithelial carcinoma may also pose a diagnostic challenge, but the potential for misdiagnosis of serous tumor of low malignant potential (S-LMP) is not well recognized. We report 13 cases of ovarian CCC with prominent papillary architecture that were initially misdiagnosed as S-LMP or low-grade serous carcinoma either on frozen section or at final diagnosis. The ages of the patients ranged from 39 to 65 years (mean, 52.2 y). All patients presented with a pelvic mass; 1 was undergoing evaluation for infertility. Macroscopically, most were described as unilateral, multilocular cysts with internal papillary structures. On microscopic examination, each tumor had a papillary architecture that accounted for 30% to 95% of the tumor; in 6 cases, the cores of the papillae were hyalinized. The neoplastic cells covering the papillae had clear to granular and eosinophilic cytoplasm. Hobnail cells were focal and often subtle. Most had a low mitotic index (9/13) and/or deceptively bland cytology (8/13); only careful attention to the cytologic features and/or mitotic index allowed correct identification of the tumor type in 5 cases. Six were associated with pelvic/ovarian endometriosis. Ten were Federation of Gynecology and Obstetrics stage I (8 IA, 2 IC), 2 were stage II (1 IIB, 1 IIC), and 1 stage IIIC. CCC with prominent papillary architecture is uncommon, but may pose a challenging differential diagnosis with S-LMP, resulting in inadequate staging and delayed treatment. Features most helpful in distinguishing papillary CCC are unilaterality, nonhierarchical branching, monomorphous cell population, and the presence of more typical CCC patterns elsewhere in the tumor. The presence of endometriosis, although not specific, should also prompt consideration for papillary CCC. Increased numbers of mitotic figures may not be present and high-grade cytologic atypia may be focal, requiring careful examination of multiple tumor sections for detection. As CCC and S-LMP exhibit significantly different immunoreactivity for Wilms' Tumor 1 and estrogen receptor, these markers may also be useful adjunctive tests in problematic cases.

Clinicopathologic significance of chromosome 17 polysomy in breast cancer

To investigate the clinicopathological significance of chromosome 17 polysomy in breast cancer. Retrospective study of 200 cases of breast cancer including 106 cases of invasive ductal carcinoma and 94 cases of in-situ carcinoma was performed by fluorescence in-situ hybridization (FISH) to explore the relationship between chromosome 17 polysomy and age, nuclear atypia, lymphatic metastasis, HER2 gene amplification and HER2 protein expression. Twenty-six percent (52/200) of chromosome 17 polysomy was detected in 200 cases of breast ductal carcinoma, all of which were invasive ductal carcinoma. Overall 52. 8% (52/180) of invasive ductal carcinoma cases showed chromosome 17 polysomy, which was correlated to HER2 gene amplification (P = 0.000) and HER-2 protein expression (P=0.000), and to HER2 expression combined with HER2 gene amplification (P=0.001). Chromosome 17 polysomy with or without HER2 gene amplification was also associated with high-grade nuclear atypia (P = 0.012 or P = 0.010) and lymphatic metastasis (P = 0.002 or P = 0.009 ). However, chromosome 17 polysomy with or without HER2 gene amplification was not correlative with the age of patients (P = 1. 000 or P = 0. 415). Chromosome 17 polysomy may be related to the nuclear atypia, metastasis, HER2 gene amplification of invasive ductal carcinoma and thus a worse prognosis of the patients.

Immunohistochemical expression of p53 and Ki67 in colorectal adenomas and prediction of malignancy and development of new polyps

The aim of this study was to investigate the immunohistochemical expression of p53 and Ki67 in colorectal adenomas in order to clarify their significance as indicators of malignancy and development of new polyps. Seventy-eight polyps were removed from 51 patients and examined. Twenty-nine patients (56.9%) had adenomas with low-grade atypia (13 of them developed new polyps at 3-year follow-up) and 22 (43.1%) had adenomas with high-grade atypia (6 of them developed new polyps at 3-year follow-up). We tested the association between p53 and Ki67 expression and various clinicopathological variables, and regression analysis was performed to identify the risk factors for malignancy and development of new adenomas. A significant correlation between the grade of atypia and p53 immunoreactivity was observed. Ki67 expression was not related to atypia and no correlation was found between p53 and Ki67 immunoreactivity. Regression analysis showed that size (p=0.0002) and p53 staining (p=0.0111) were the selected factors related to malignant transformation, whereas the number of synchronous primary polyps emerged as the only predictive factor of development of new adenomas, although without statistical significance. The expression of biological markers may be in future added to the currently examined features of polyps; however, further studies are needed to better define their predictive value.

Acinar Pattern of Mammary Paget?s Disease: A Case Report

Mammary Paget's disease (MPD) is an uncommon in situ neoplasm of the nipple-areolar complex and surrounding skin. It is almost always associated with mammary ductal carcinoma in situ (DCIS), high-grade or invasive carcinoma, usually of ductal origin. MPD has only rarely been described in association with specialized forms of breast carcinoma. We report an unusual case of an acinar pattern of MPD with low-grade cytological atypia, associated with invasive papillary carcinoma and micropapillary DCIS of the lactiferous ducts, in an 83-year-old woman. Most cases of MPD are characterized by intraepidermal spread of discohesive glandular epithelial cells with high-grade nuclear atypia. A predominant acinar pattern of MPD is extremely uncommon and, to our knowledge, has not been formally reported. The histological features and differential diagnosis are discussed.

Intraductal carcinoma is the precursor of carcinoma ex pleomorphic adenoma and is often associated with dysfunctional p53

Although intraductal carcinoma has been demonstrated in intracapsular carcinoma ex pleomorphic adenoma (CEPA), the morphological and genetic stages of transformation of pleomorphic adenoma (PA) to CEPA are not fully understood. The aim of this study was to investigate the morphology of intracapsular CEPA. The largest series of intracapsular CEPA studied was subject to immunohistochemical double-staining to detect p53 protein and cellular proliferation in different types of cell combined with mutational analysis of the p53 gene in laser-microdissected material. Intraductal carcinoma with high-grade cellular atypia and frequent accumulation of p53 protein was found in 15/19 cases. Purely intraductal carcinoma was found in eight cases. Mutation of p53 was found in 7/19 cases, of which it was found in intraductal carcinoma in 5/15 cases. The frequent demonstration of intraductal carcinoma indicates that this preinvasive lesion is likely to be a constant feature in the malignant transformation of PA to CEPA. It appears to be a feature of CEPA developing from both primary and recurrent PA. The combined immunohistochemical and genetic data show that 14/19 cases of CEPA and 11/15 cases with intraductal carcinoma showed genetic or morphological evidence of dysfunctional p53, indicating that this is an early event in malignant transformation.

Gastric and Intestinal Phenotypic Marker Expression in Early Differentiated-Type Tumors of the Stomach: Clinicopathologic Significance and Genetic Background

Gastric and intestinal phenotypic cell markers are expressed in gastric carcinomas, irrespective of their histologic type. In the present study, we determined the clinicopathologic significance of phenotypic marker expression in early-stage gastric differentiated-type tumors and the association between marker expression and genetic alterations. Phenotypic marker expression was determined by examining the expressions of human gastric mucin (HGM), MUC6, MUC2, and CD10 in 63 gastric adenomas, 133 early differentiated-type carcinomas, and 24 follow-up cases with gastric adenoma. Tumors were classified into gastric, gastric and intestinal mixed, or intestinal phenotypes according to the immunopositivity of the above markers. The presence of mutations in APC, K-ras, and p53 and the microsatellite instability status were also determined in all tumors. The expressions of HGM and MUC6, representing gastric or gastric and intestinal mixed phenotypes, were significantly associated with high-grade atypia in the 63 gastric adenomas. Among the 133 early differentiated-type carcinomas, HGM expression was significantly associated with mixed-type (with an undifferentiated-type component) tumors and lymph node metastasis. MUC2 expression was inversely associated with submucosal invasion. A multivariate analysis revealed that gastric adenomas were significantly associated with the intestinal phenotype and were inversely associated with p53 mutation compared with early differentiated-type carcinomas. Among all 196 tumors, APC mutation was significantly associated with CD10 expression and the intestinal phenotype and was inversely associated with the expressions of HGM and MUC6. The microsatellite instability status was significantly associated with MUC6 expression. Malignant transformation from gastric adenoma to carcinoma was shown in 5 of the 24 follow-up cases of gastric adenoma. The malignant transformation was significantly associated with the gastric and intestinal mixed phenotype and was inversely associated with APC mutation. No malignant transformation was found in intestinal phenotype gastric adenomas with APC mutation. Our present findings show that phenotypic marker expression is associated with tumor aggressiveness during the early stage of gastric differentiated-type tumors. Differences in the biological behavior of tumors with different phenotypes may result from differences in the genetic backgrounds during the incipient phase of gastric tumorigenesis.

Lokale Nachexzision nach endoskopischer R1/R2-Polypektomie von pT1-„low-risk”- Karzinomen des Rektums durch transanale endoskopische Mikrochirurgie (TEM)

The transanal endoscopic microsurgery (TEM) is an adequate method for the local full-thickness excision of large rectum polyps and pT1 "low-risk" rectal carcinomas. We studied prospectively the relevance of this surgical technique concerning complete tumour excision after R1/R2-polypectomy of malignant rectal polyps. 16 patients with pT1 "low-risk" rectal carcinoma and macroscopic (R2) or microscopic (R1) incomplete endoscopic polypectomy were locally resected by TEM. In 12 patients (75 %) no residual tumour was found. In the remaining four cases (25 %), one adenoma with high-grade atypia, two pT1 "low-risk" carcinomas and one tumour infiltration in the mesorectal fat were diagnosed. The patient with the mesorectal infiltration was immediately operated on with radical resection. No further tumour cells were found in this specimen. The median follow-up was 21 months. One patient with a pT1 "low-risk" carcinoma developed a local recurrence and a single hepatic metastasis in the left liver lobe after TEM. Both were completely resected. Currently, all patients are living without evidence of tumour recurrence. Transanal endoscopic microsurgery is a suitable method for the treatment of pT1 "low-risk" rectal carcinomas after incomplete endoscopic polypectomy. In cases of a "high-risk" tumour or deeper tumour infiltration (pT> 1) after TEM radical resection must be carried out.

Intraductal papillary mucinous neoplasm (IPMN) of the gastric-type with focal nodular growth of the arborizing papillae: a case of high-grade transformation of the gastric-type IPMN

We present a case of intraductal papillary mucinous neoplasm (IPMN) of the pancreas, demonstrating a process of high-grade transformation of the gastric-type IPMN. An 83-year-old Japanese woman underwent pylorus-preserving pancreatoduodenectomy for removal of a multicystic mass of the pancreas head, which had been followed up for 7 years. The removed tumor was a low-grade gastric-type IPMN spreading in the branch ducts, focally forming an intraluminal nodular lesion. The nodular lesion was comprised of arborizing papillotubular proliferation of cuboidal to columnar epithelia with high-grade atypia, and was characterized by diffuse MUC1 expression and a gastric mucin phenotype (focal MUC5AC and MUC6 expressions). Therefore, the nodular lesion was consistent with the pancreatobiliary-type IPMN, and the present case suggests that the low-grade gastric-type IPMN may progress to a focal intraductal carcinoma over the years, and the pancreatobiliary-type IPMN may be one of the forms of such high-grade transformation of the gastric-type IPMN. One of the cystic lesions was an oligocystic-type serous cystic neoplasm (serous cystadenoma), which might be an incidental concomitance or have a common basis.

Soft tissue myoepithelial carcinoma

Myoepitheliomas are tumors composed predominantly or exclusively of myoepithelial cells, usually arising in salivary glands. Cutaneous/soft tissue localization is very rare, especially for the malignant myoepitheliomas. We presented a case of myoepithelial carcinoma involving subcutaneous adipose tissue of the left forearm in a woman aged 62 years. The tumor was composed of epithelioid and hyaline cell types, arranged in diffuse sheets, nests and loose clusters within hyalinized and myxoid matrix. The neoplasm displayed high-grade cytologic atypia with some cells having pleomorphic, hyperchromatic nuclei, and others showing vesicular nuclei, large nucleoli with scattered bizarre giant cells. High mean mitotic count of 7 mitoses/10 high power filds and extensive necrosis favoured the diagnosis of malignancy. Immunohistochemical staining was positive for cytokeratin (AE1/AE3), epithelial membrane antigen, S-100 protein, glial fibrillary acidic protein, and vimentin. Considering the subcutaneous localization, myoepithelial immunophenotype and high-grade cytologic atypia the neoplasm was classified as a soft-tissue myoepithelial carcinoma.

Locally Recurrent Central-Type Early Stage Lung Cancer < 1.0 cm in Diameter After Complete Remission by Photodynamic Therapy

It is well known that central-type early stage lung cancer < 1.0 cm in diameter shows almost 100% complete response (CR) to photodynamic therapy (PDT). However, we have encountered cases of local recurrence after CR of tumors with a surface diameter < 1.0 cm. Ninety-three patients with 114 lesions were followed up, and cases of recurrence after CR has been obtained with initial tumors that had a diameter < 1.0 cm were examined. We compared the cytologic findings of local recurrence after CR to the cytologic findings before PDT. The relationship between the cell features and the depth of bronchial tumor invasion before PDT and on recurrence was evaluated. The CR and 5-year survival rates of patients with lesions < 1.0 cm were 92.8% (77 of 83 patients) and 57.9%, respectively; meanwhile, in the group of patients with lesions > or = 1.0 cm, CR and 5-year survival rates were 58.1% (18 of 31 patients) and 59.3%. There was a significant difference in efficacy between the two groups (p < 0.001). Recurrences after CR were recognized in 9 of 77 lesions (11.7%) < 1.0 cm. When the recurrent tumor cells showed type I-II (low-to-moderate atypia) at the same site initially treated, CR could be obtained by a second PDT. Type III cells (high-grade atypia) showed the characteristics of tumor cells from deeper layers of the bronchial wall. Local recurrence at the same site may be caused by residual tumor cells from deep layers because of inadequate laser irradiation and penetration. To reduce the recurrence rate, it is essential to accurately grasp the tumor extent and the depth of the bronchogenic carcinoma before performing PDT. Analysis of cell features of recurrent lesions after CR appears to be a useful source of information as to the depth of cancer invasion in the bronchial wall.

Prostate cancer detection and tumor characteristics in men with multiple biopsy sessions

To address prostate cancer (PCa) detection with respect to the number of biopsy sessions performed, to identify risk factors for detection after a negative biopsy, and to analyze the clinical characteristics of the detected tumors. Only biopsied men (sextant) were included. A total of 1011 biopsy sessions were carried out in 770 men; 172 underwent a second prostate biopsy and 51 a third biopsy. During the first biopsy round, 111 cancers were found (14.4%), 27 in the second (15.7%), and five during the third round (9.8%), P=0.156. Only high-grade PIN or atypia were identified as independent predictors or PCa detection in subsequent biopsies (P=0.008). A nonsignificant increase of clinically localized tumors, and a decrease of metastatic and poorly differentiated cases were found when more biopsy sessions were needed for detection. A nonsignificant trend to lower cancer detection rates and less clinical relevance of the tumors detected can be observed when more biopsy rounds are needed for detection.

Cellular nodules in congenital pattern nevi.

The diagnosis of 'cellular dermal nodule in melanocytic nevi' is challenging, as it can simulate invasive and tumorigenic melanoma. Because cellular nodules are presumed benign, it is essential to differentiate them from true malignant melanoma arising within a nevus, which portends a poor prognosis. Although presumed benign, to date, no published long-term follow-up studies have proved the benignity of this lesion. To better understand the clinical behavior and histological features of these lesions, we present a clinical pathological study of a cohort of 26 cases, for which we obtained clinical follow up by chart review and questionnaires. Clinical follow up was obtained on 16 out of 26 patients (61.5%) and ranged from 12 to 132 months (average 62.3 months). The cellular nodules in congenital pattern nevi, reported here, had an invariably benign clinical course. Features useful in differentiating cellular nodule from melanoma include: (1) lack of high-grade uniform cellular atypia; (2) lack of necrosis within the nodule; (3) rarity of mitoses; (4) evidence of maturation in the form of blending or transitional forms between the cells in the nodule and the adjacent nevus cells; (5) lack of pagetoid spread into the overlying epidermis; and (6) no destructive expansile growth. The difference between cellular nodule and melanoma arising from nevus can be very subtle, and it is important to emphasize that these lesions must be assessed on an individual case-by-case basis.

Appendiceal mucinous neoplasms: a clinicopathologic analysis of 107 cases.

The classification of appendiceal mucinous tumors is controversial and terminology used for them inconsistent, particularly when they lack overtly malignant features but are associated with extra-appendiceal spread. We reviewed 107 appendiceal mucinous neoplasms and classified them as low-grade appendiceal mucinous neoplasm (LAMN) (n = 88), mucinous adenocarcinomas (MACAs) (n = 16), or discordant (n = 3) based on architectural and cytologic features. LAMNs were characterized by a villous or flat proliferation of mucinous epithelium with low-grade atypia. Thirty-nine tumors were confined to the appendix, but 49 had extra-appendiceal tumor spread, including 39 with peritoneal tumor characterized by mucin pools harboring low-grade mucinous epithelium, usually dissecting in a hyalinized stroma. Eight of the 16 MACAs lacked destructive invasion of the appendiceal wall and eight showed an infiltrative pattern of invasion. Extra-appendiceal tumor spread was present in 12 MACAs (four peritoneum, seven peritoneum and ovaries; one ovaries only). In MACAs with an infiltrative pattern, peritoneal tumor consisted of glands and single cells in a desmoplastic stroma. The peritoneal tumor in the remaining cases consisted of mucin pools that contained mucinous epithelium with high-grade atypia and, in some cases, increased cellularity compared with that seen in peritoneal spread in cases of LAMN. Three cases were classified as discordant because the appendiceal tumors were LAMNs but the peritoneal tumors were high-grade. Follow-up was available for 49 LAMNs, 15 MACAs, and 2 discordant cases. None of the patients with LAMNs confined to the appendix experienced recurrence (median follow-up 6 years). LAMNs with extra-appendiceal spread were associated with 3-, 5-, and 10-year survival rates of 100%, 86%, and 45%, respectively. Patients with MACA had 3- and 5-year survival rates of 90% and 44%, respectively (p = 0.04). The bulk of peritoneal disease correlated with prognosis among patients with MACA (p = 0.04) and, to a lesser degree, among patients with LAMNs (p = 0.07). We conclude that: 1) appendiceal mucinous neoplasms can be classified as either low-grade mucinous neoplasms or mucinous adenocarcinoma based on architectural and cytologic features; 2) tumors that can be confidently placed in the low-grade group (which requires rigorous pathologic evaluation of the appendix) and are confined to the appendix are clinically benign in our experience to date; 3) low-grade tumors confined to the appendix are morphologically identical to those with extra-appendiceal spread (except for the usual identification of breach of the wall in the latter cases) and the same designation is appropriate for the appendiceal neoplasia in each situation; 4) the long-term outlook for patients with low-grade tumors and peritoneal spread is guarded with just over half dying of disease after 10 years; 5) appendiceal mucinous tumors with destructive invasion of the appendiceal wall, complex epithelial proliferations, or high-grade nuclear atypia generally pursue an aggressive clinical course and should be classified as mucinous adenocarcinomas; 6) peritoneal tumor can be classified as involvement by LAMN or MACA, and this distinction is of prognostic significance; 7) bulky peritoneal tumor worsens prognosis; and 8) LAMNs associated with high-grade peritoneal tumor behave as adenocarcinoma.

Usefulness of endoscopic biopsy using immunostaining of p53 and Ki-67 in tumors of the ampulla of Vater.

We investigated the diagnostic and prognostic value of p53 expression and proliferative activity, as indicated by the Ki-67, in endoscopic biopsy specimens. Specimens were immunologically stained with p53 and MIB-1 (Ki-67), and the MIB-1/Ki-67 labeling index (LI) was calculated. Classification of adenomas was based on findings of H&E-stained preparations into those with low- or high-grade atypia. Well-differentiated tubular and papillary adenocarcinomas were classified as carcinomas with low- or high-grade atypia. There were significant differences among the control and adenoma patients in MIB-1/Ki-67 LI (P < 0.05). No significant difference was identified between adenomas with high grade atypia and carcinomas with low grade atypia. The p53 expression was negative in all adenomas, but it was positive in 68.2% of carcinomas. The current study demonstrated that p53 protein expression in endoscopic biopsy specimens was of preoperative diagnostic value for carcinoma of the ampulla of Vater. The p53 protein positive tumors had a relatively higher malignant potential than p53 protein negative ones. The MIB-1/Ki-67 LI was useful in differentiating non-tumorous lesions from adenomas and adenomas with low- or high-grade atypia. The MIB-1/Ki-67 LI had a prognostic value because clinicopathological factors of carcinoma of ampulla of Vater correlated with MIB-1/Ki-67 LI.

The characteristics of early bronchogenic carcinoma evaluated by cytomorphological features

The relationship between the cell features of central type early lung cancer and the degree of invasion to the bronchial wall was investigated. Bronchial brushing specimens were obtained from 19 cases of central type early lung cancer preoperatively and the resected specimens were pathologically examined. The cell features were classified into three types: Type I: low grade atypia without increased nuclear chromatin, Type II: moderate grade atypia with increased chromatin and Type III: high grade atypia with irregular shaped nucleus and increased chromatin. The expression of Type I cells was significant in cases of carcinoma in situ or microinvasion and Type II and III cells were observed more frequently in cases with extramuscular bronchial wall invasion. The cell features as well as endoscopic findings can provide a basis for the more precise staging of early stage lung cancer and the determination of therapeutic strategy.

Histogenesis and morphogenesis of depressed-type early colorectal carcinoma.

The aim of this study was to elucidate the histogenesis and morphogenesis of depressed-type early colorectal carcinomas (DECas). Eighty-seven DECas were selected for examination. The 87 DECas included 23 (26.4%) absolutely depressed (ABS) types (depressed mucosa being thinner than the normal mucosa; histologically true depression), 40 (46.0%) relatively depressed (REL) types (the thickness of the depressed mucosa being the same or greater than that of normal mucosa, with depression being relative compared to marginal elevation) and 24 (27.6%) ulcerated (UL) types (no remnant intramucosal component in the depressed area). The rates of residual adenomatous components were 0/23 (0%) for ABS type and 12/40 (30%) for REL type, indicating that the ABS type was thought to have arisen de novo and the REL type was thought to have arisen de novo and via an adenoma-carcinoma sequence. In 13 of the 23 (56.5%) ABS types, carcinoma was located within the depressed area alone, suggesting that many ABS types show a depression from their initial stage. While 33 of the 40 (82.5%) REL types accompanied by marginal elevation consisted of neoplastic mucosa, in 19 of the 33 (57.6%) cases, the depressed area showed a higher grade of atypia than the area of marginal elevation. This suggested that the depression in the REL type was generated secondarily at the center of a pre-existing, superficially elevated tumor due to progression of its histological grade of atypia. ABS type was speculated to be the precursor of UL type since the two types showed similarity (no statistical significant difference) in percent depression (69.6 vs 64.3%), grade of atypia of carcinoma (52.2 and 79.2% consisted of carcinoma with high-grade atypia alone), and frequency of being accompanied by non-neoplastic reactive marginal elevation (56.5 vs 70.8%).

Type-Ip colon cancer bearing surface erosions where we had a great difficulty in establishing the cancerous depth diagnosis

A 75-year-old male turned out positive for the fecal occult blood test without any complaints. A pedunculated but broad-based lesion measuring about 10mm and lacking in mobility was discerned in the sigmoid colon, the top of which assumed an asymmetric and expansive growth. The surface looked uneven and reddened causing haemorrhagic fragility resulting in the formation of depressed erosions and nodules, which was deduced to be indicative of sm2 or deeper cancer. Barium enema likewise revealed no mobility. The entire lesion comprised VI pit, and VN pit was also discerned in depressed portions. Pathologically, well to moderately differentiated cancer (high grade atypia) without adenoma component, cancerous depth sm1, ly0, v0, cut end (－) , interstitial permeation from the bottom of glands present. Despite the features indicative of sm2 or deeper, the lesion resulted in minimally invasive sm1. The present case cautioned us not to make an over-diagnosis between mucosal and sm2 cancer in that there actually exists the limitation or the very difficulty in the clinical diagnosis concerned.

Morphologic expressions of urothelial carcinoma in situ: a detailed evaluation of its histologic patterns with emphasis on carcinoma in situ with microinvasion.

The recently proposed World Health Organization/International Society of Urological Pathology (WHO/ISUP) consensus classification of flat urothelial lesions expands the definition traditionally used for urothelial (transitional cell) carcinoma in situ (CIS), basing its diagnosis predominantly on the severity of cytologic changes. Lesions now encompassed within the diagnosis of CIS exhibit an array of cytologic and architectural features, which have not been documented in detail. In this study, cases were examined with respect to histologic patterns and microinvasion (invasion into the lamina propria to a depth of less than 2 mm). Five major patterns of CIS, often occurring in the same specimen (160 patterns in 77 cases), were noted. Common to each pattern was the presence of high-grade cytologic atypia, the definitional feature. The patterns found include 1) large cell CIS with pleomorphism (57%), in which the cells had abundant cytoplasm and nuclear pleomorphism; 2) large cell CIS without nuclear pleomorphism (48%); 3) small cell CIS (14%), in which the cytoplasm was relatively scant and pleomorphism was usually minimal; 4) clinging CIS (40%), in which the urothelium was denuded with a patchy, usually single layer of atypical cells; and 5) cancerization of urothelium (16%) with either pagetoid spread (clusters or isolated single cells) or undermining or overriding of the normal urothelium. Carcinoma in situ with microinvasion into the lamina propria (13 cases: 3 of 77 CIS cases studied above and 10 additional cases) was evident as invasive cells with retraction artifact mimicking vascular invasion (77%, 10 cases); nests, irregular cords, and strands, or isolated single cells with desmoplasia (8%, 1 case); or absent stromal response (15%, 2 cases). Although the diagnostic terminology for all of these patterns, for the purposes of the surgical pathology report, should be simply urothelial CIS with no specific mention of the morphologic pattern, awareness of the histologic diversity of CIS will facilitate the diagnosis of this therapeutically and biologically critical flat lesion of the urothelium. These lesions may be associated with microinvasion, which may be clinically unsuspected and histologically subtle.