Invasive colorectal micropapillary carcinoma: an aggressive variant of adenocarcinoma

Micropapillary carcinoma (MC) has been well described in other organs, including breast, urinary bladder, lung, ovary, and salivary gland, but has not been described in the large intestine. We compared the clinicopathologic and immunohistochemical findings of MC with those of conventional adenocarcinoma in the large intestine. Fifty-five cases of adenocarcinoma with an MC component were identified among 585 consecutive cases of colorectal cancer at the Asan Medical Center between January 2003 and June 2004 and were compared with 119 cases of conventional adenocarcinoma of colorectum without an MC component. Arrayed tissue blocks were constructed and immunostained for cytokeratin 7 and 20 and CDX2. We also compared the results of MLH-1, MSH-2, p53, and carcinoembryonic antigen immunostainings between the 2 groups. The grade of both MC and conventional adenocarcinoma was mostly moderately differentiated. The proportion of MC ranged from 5% to 80%. The presence but not extent of MC in the primary tumors was associated with more frequent lymphovascular invasion and lymph node (LN) metastases, a greater mean number of positive LNs, and a higher tumor stage with more frequent distant metastases, compared with conventional adenocarcinoma (P < .05). Cytokeratin 7 staining was occasionally observed in both MC (9.1%, 5/55 cases) and conventional adenocarcinoma (13.4%, 16/119 cases). Although MLH-1 and CDX2 expression tended to be lower in conventional adenocarcinoma, none of the immunohistochemical results was significantly different between 2 groups. Recognition of MC component is important as MC appeared to be an aggressive variant of colonic adenocarcinoma and presented at a higher stage, with frequent lymphovascular invasion, LN metastasis, and distant metastasis, compared with conventional adenocarcinoma. The proportion of MC component did not impact the prognosis, and the immunoprofiles of MC were not significantly different from those of conventional adenocarcinoma.     

Pure invasive micropapillary carcinoma of the male breast: Report of a rare case with C-MYC amplification

Male breast cancer is rare. The most common histological subtypes include invasive carcinoma “of no special type” and papillary carcinoma. Other variants, including pure micropapillary carcinoma, have been described as well but are extremely rare. Pure micropapillary carcinoma has been recently characterized by a C-MYC gene amplification in women.We report here, occurring in a 73-year-old man, the first case of pure micropapillary carcinoma with amplification of the C-MYC gene.     

Mucinous breast carcinoma and mixed mucinous-infiltrating ductal carcinoma: a comparative cytologic study

In its pure form, mucinous breast carcinoma (MC) has a much better prognosis than infiltrating ductal carcinoma (IDC). Mixed MC-IDC has the prognosis of IDC. We compared the fine-needle aspiration (FNA) cytology and histology of nine cases of pure MC with 13 cases of mixed MC-IDC. While typical of pure MC, abundant mucin (3+/3+) was noted in smears from three cases of mixed tumor and is thus necessary but not sufficient for a diagnosis of pure MC. Cellular pleomorphism has been said not to be a feature of MC; however, we found occasional large cells markedly different from the typical small uniform cells of MC in four pure and seven mixed tumors. Cytologic features indicative of a mixed tumor include one or more smears totally without mucin, scantly amounts of mucin, or necrosis. A combination of features indicative of pure mucinous carcinoma in FNA included abundant mucin on all smears, no pleomorphism, and no necrosis. Many cases will have smear patterns that are not typical of either profile and should probably be designated as carcinoma with a mucinous component.     

Micropapillary carcinoma of the parotid gland arising in mucinous cystadenoma

We describe a 45-year-old man who had a 2-year history of a slowly enlarging tumor in the left parotid gland. Histologically, the tumor was a mucinous cystadenoma with focal apocrine differentiation, which revealed a widespread invasive micropapillary adenocarcinoma component. A rim of lymphoid tissue surrounded the margins of the micropapillary carcinoma. The invasive micropapillary adenocarcinoma component was morphologically identical with the invasive micropapillary carcinoma of the mammary gland. The tumor is different from so-far recognized salivary gland tumor entities. Received: 25 October 1999 / Accepted: 13 June 2000     

Thyroid gland papillary carcinomas with "micropapillary pattern," a recently recognized poor prognostic finding: clinicopathologic and survival analysis of 7 cases

Micropapillary carcinoma is a histologic pattern, rather than an independent entity, that has an aggressive clinical behavior regardless of location. Histologically, it is characterized by papillary cell groups in clear spaces. The micropapillary pattern in the thyroid gland has not been studied until recently but under other names such as hobnail features or oncocytic and, therefore, is poorly understood, and reported cases are few. We report the clinicopathologic features of 7 cases obtained from a cohort of 496 papillary thyroid carcinomas, which corresponds to a prevalence of 1.4%. The proportion of the micropapillary component accounted for between 5% and 20% of the tumors, was slightly more prevalent in men, correlated with the presence of lymphovascular permeation, and, in the survival analysis, showed lower survival (even at a short follow-up, 8.5 years) than conventional carcinoma without this component (P = .001); this is consistent with poor overall survival in the short term (2-5 years) reported for carcinomas with micropapillary pattern of other locations. We believe that owing to this difference in survival (>95% of patients with conventional papillary carcinoma are alive at 8.5 years versus 42% of those having at least 5% of micropapillary pattern), the micropapillary pattern should be correctly identified and stated in the pathology report when comprising at least 5% of the tumor.     

KL-6 is another useful marker in assessing a micropapillary pattern in carcinomas of the breast and urinary bladder,but not the colon

To evaluate the peculiar “inside-out” pattern in micropapillary (MP) carcinoma, we investigated the usefulness of KL-6 antibody in the assessment of the MP pattern of cancers, in comparison with antibodies to epithelial membrane antigen (EMA), MUC1 (CD227), and CD 10. Immunohistochemical investigation was performed on specimens exhibiting an MP pattern obtained from 12 persons with cancer: 4 with breast carcinoma, 3 with carcinoma of the urinary bladder, and 5 with colonic carcinoma. Immunohistochemical study with KL-6, EMA, and MUC1 antibodies revealed similar continuous linear positive patterns restricted to the surface of the MP pattern in both breast and urinary bladder cancers, revealing the peculiar “inside-out” morphology. However, EMA also gave cytoplasmic positivity in most of the cases tested, and MUC1 was also present in the cytoplasm of some cases. In sharp contrast, immune reactions of colon carcinomas with these antibodies were negative, except for focal positivity for KL-6 and MUC1 antibodies in some cases. CD10 was only focally positive in an MP pattern in 4 of the 5 cases of colon carcinoma and in 1 case with carcinoma of the urinary bladder. These findings suggest that KL-6 is a useful marker to assess the MP character of breast and urinary bladder carcinomas; that MUC1 was similarly positive, with the addition of cytoplasmic positivity in some cases; and that the MP pattern of colon cancer, positive for CD 10, was different in character from both breast and urinary bladder carcinomas, although all these cancers seemingly exhibit similar MP patterns on histopathology. This heterogeneity of the MP pattern in various cancers needs to be investigated when more cases have been accumulated.     

Prognostic significance of micropapillary pattern in pure mucinous carcinoma of the breast

Breast carcinoma with micropapillary architecture is associated with aggressive behavior. Similar micropapillary pattern in pure mucinous carcinoma has been noticed and has been shown to convey poor prognosis. In this study 17 cases of pure mucinous carcinoma of the breast seen during a 10-year period have been reviewed, with special reference to micropapillary pattern. Diffuse micropapillary pattern was seen in 6 of 17 cases of mucinous carcinoma of the breast and demonstrated reverse polarity immunostaining pattern with "Epithelial Membrane Antigen." In all cases, the tumor cells showed grade I morphology, and no lymph node metastases were noticed. All the tumors except 1 expressed strong estrogen and progesterone receptor expression, however, all the cases were negative for Her-2/neu expression. In this present study, mucinous carcinomas with micropapillary pattern showed a low nuclear grade, higher incidence of hormone receptor positivity, and lower incidence of Her-2/neu similar to mucinous carcinomas without micropapillary pattern, thus explaining their indolent behavior.     

Invasive mucinous cystic neoplasms of the pancreas

Mucinous cystic neoplasms (MCN) and intraductal papillary mucinous neoplasms (IPMN) of the pancreas both appear to have been included and intermixed in some early reports of pancreatic cystic neoplasms. Recognition of their distinguishing features evolved during the last decade of the twentieth century. One legacy of the early period is the statement that mucinous cystic neoplasms sometimes progress to invasive colloid carcinoma. It is now recognized that colloid carcinomas characteristically arise from IPMN. We set out to see if we could find MCN that invaded as colloid carcinomas and found no examples in MCN collected in two academic medical centers. We then sought to expand the number of MCN by evaluating series from additional centers. This yielded no examples of colloid carcinomas associated with 291 MCN, however one MCN exhibited a minor component with colloid (non-cystic mucinous) growth pattern within the fibrous wall of the neoplasm. The expression of CDX2, a marker of intestinal differentiation that is found in colloid carcinomas was examined by immunostaining in the original MCN series and in the MCN with the intratumoral colloid growth pattern. Focal expression of CDX2 was found in 22 of 43 MCN including the MCN that exhibited the intratumoral colloid growth pattern. Overall, the data suggest that MCN rarely, if ever, invade as colloid carcinoma but the expression of CDX2 by some MCN and the observation of intratumoral colloid growth pattern in one MCN seems to leave open the possibility that MCN might rarely invade as colloid carcinoma.     

Absence of microsatellite instability in mucinous carcinomas of the breast

Microsatellite instability (MSI) is a form of genetic instability that results from defects in DNA mismatch repair. MSI is reported to be rare in unselected breast cancers, however it is a common feature in subsets of colorectal, ovarian and endometrial cancers. In these anatomical sites, MSI-high carcinomas often display a mucinous histology. The aim of this study was to determine whether mucinous carcinomas of the breast would more frequently display MSI-high than invasive ductal carcinomas of no special type (IDC-NSTs). The expression of four MSI markers (i.e. MSH2, MSH6, MLH1 and PMS2) was immunohistochemically assessed in 35 mucinous breast carcinomas and 35 histological grade- and oestrogen receptor (ER) status-matched IDC-NSTs, and in a series of 245 invasive breast cancers. Cases were considered as potentially MSI-high if tumour cells lacked expression of at least two MSI markers and internal controls displayed nuclear staining. Nine mucinous carcinomas were microdissected and subjected to MSI analysis by PCR using the MSI markers BAT26 and BAT40. No immunohistochemical evidence of MSI-high was found in the 35 mucinous carcinomas and 35 grade- and ER-matched IDC-NSTs, and in the cohort of 245 invasive breast cancers. In addition, no evidence of MSI-high was observed by PCR analysis using the BAT26 and BAT40 markers in the nine mucinous carcinomas tested. Our results demonstrate that MSI-high phenotype is remarkably rare in invasive breast cancer, and that, in contrast to mucinous carcinomas of other anatomical sites, MSI is not a common event in mucinous carcinomas of the breast.     

Expression of p53 protein in benign epithelial hyperplasia,atypical ductal hyperplasia,non-invasive and invasive mammary carcinoma: an immunohistochemical study

To clarify whether p53 protein expression is involved in multistep carcinogenesis or the progression of mammary ductal carcinoma, we investigated p53 protein expression in 83 invasive ductal carcinomas (IDC), 10 IDC with a predominant intraductal component, 13 non-invasive ductal carcinoma (NIDC), 16 atypical ductal hyperplasia (ADH) and 39 benign epithelial hyperplasia (EH), using immunohistochemistry. Expression of p53 protein was detected in 24 (28.9%) cases of IDC, 5 (50%) cases of IDC with a predominant intraductal component and 1 (7.6%) case of NIDC. No expression was observed in either ADH or EH. In IDC, including cases with a predominant intraductal component, p53 protein expression was associated with a higher histological grade (P<0.0001) or mitotic index (P<0.0005). Although overexpression of c-erbB-2 protein has also shown a similar association with these prognostic indicators, expression of p53 protein correlated regardless of the status of c-erbB-2 overexpression. Completely coordinated expression of p53 protein was seen in both intraductal and invasive components. The intraductal component in IDC including cases with a predominant intraductal component which expresses p53 protein had significantly higher histological grade (P<0.0005) or more comedo-subtypes (P<0.0001). These results suggested that p53 protein expression occurs at a stage of NIDC with high histological grade or in comedo-subtypes. Its expression is maintained throughout invasion.     

Primary squamous cell carcinoma of the thyroid gland: an entity with aggressive clinical behaviour and distinctive cytokeratin expression profiles

AIMS: Primary squamous cell carcinoma of the thyroid gland is uncommon. This study aims to identify the clinicopathological features and the pattern of expression of cytokeratins and oncoproteins in this tumour. METHODS AND RESULTS: Histological slides from Chinese patients with thyroid cancer treated in our institution from 1980 to 1999 were reviewed. Patients with primary squamous cell carcinoma of the thyroid were identified and their clinical records were analysed. The expression of cytokeratins (CKs), p53 and p21 in these cases were also studied by an immunohistochemical method. Four women (mean age 71 years) with squamous cell carcinoma of thyroid were found. The main presenting features were signs and symptoms of airway obstruction in three patients and neck swelling in one. The tumours were located at the right lobe (n=2), left lobe (n=1) or in both lobes of the thyroid (n=1). One patient died shortly after admission and the other three died within 4 months after thyroidectomy. The p53 protein was positive in 50% (2/4) of the tumours and p53+ tumours were poorly differentiated. The tumours were negative for p21. CK19 was expressed in all the tumours while CK7 expression was noted in 3/4 of the tumours. One carcinoma showed focal positivity to CK18. The tumours were negative for CKs 1, 4, 6, 10/13 and 20. The pattern of cytokeratin expression in squamous cell carcinoma of the thyroid gland was different from carcinoma showing thymus-like differentiation (CASTLE) of the thyroid gland and oesophageal squamous cell carcinoma. CONCLUSIONS: Squamous cell carcinoma of the thyroid has aggressive clinical behaviour and characteristic CK expression pattern. p53 over-expression in these tumours was associated with tumour differentiation.     

p53 expression related to the aggressive infiltrative histopathological feature of basal cell carcinoma

AIMS: To determine whether the p53 protein expression which is involved in the genesis and progression of various malignant tumours may relate to age, sites or the aggressive histopathological feature of the basal cell carcinoma.METHODS ADN RESULTS: One hundred and fifty-eight basal cell carcinoma specimens from Songklanakarind Hospital, southern Thailand, collected from January 1992 to December 2000, were examined by immunohistochemistry using polyclonal anti-p53-CM1 (Novocastra Laboratories, Newcastle, UK; dilution 1:700). p53 protein expression was demonstrated in 48.7% of cases. The multivariate analysis showed that the aggressive infiltrative histopathological type was significantly associated with p53 expression (odds ratio 2.95, 95% confidence interval 1.10-7.90), whereas age, sun-exposure site, cellular response and fibrosis were not.CONCLUSIONS: The p53 expression is found to be related to the aggressive histopathological feature, which may be of predictive value for the behaviour of basal cell carcinoma. However, this result does not support the relation between sun exposure inducing basal cell carcinoma and p53 protein expression.     

Clinicopathological significance of invasive micropapillary carcinoma component in invasive breast carcinoma

Invasive micropapillary carcinoma (IMP) of the breast is a rare variant of invasive breast carcinoma and most cases of IMP are associated with nodal metastasis and lymphatic invasion. Lesions composed of an IMP component alone are rare and almost always coexist with other pathological components. However, few reports have documented IMP along with its proportion and the coexistent pathological type. We analyzed the total 486 breast cancer lesions operated in our hospital in 1998. We classified the lesions into five groups by the proportion of the IMP component in each lesion. Then we evaluated the incidence of nodal metastasis and lymphatic invasion in each group. The incidence of the invasive carcinoma containing any IMP components was 8.4%. The incidence of nodal metastasis and lymphatic invasion in lesions with an IMP component were significantly higher than that in those with no IMP. No correlation was seen between the incidence of nodal metastasis and the coexistent pathological type, shape of tumor clusters, nuclear grade and the expression of estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2 and gross cystic disease fluid protein-15 in IMP components. The presence of IMP components was a significant predictive factor for nodal metastasis, even if it is detected in only a small proportion of the tumor.