Aggressive invasive micropapillary salivary duct carcinoma of the parotid gland

The presence of invasive micropapillary component has been reported to be associated with salivary duct carcinoma and poor outcomes. Herein is described a rare case of invasive micropapillary salivary duct carcinoma of the parotid gland in a 60-year-old man. The micropapillary component was approximately 70% of the area of the tumor. Squamous differentiation was focally seen adjacent to the micropapillary component. On immunohistochemistry the ordinary salivary duct carcinoma component was positive for gross cystic disease fluid protein-15 (GCDFP-15), androgen receptor (AR), and HER2/neu, whereas both micropapillary and squamous components were negative for GCDFP-15 and AR. Immunohistochemical staining for D2-40 highlighted the lymph vessel invasion of tumor cells. This patient developed metastases in the lymph nodes of the neck, and also in the liver, lung, and brain. The lymph nodes and liver metastases had both ordinary salivary duct carcinoma and micropapillary components. The patient died of tumor 11 months after the initial surgical operation. The results support that the presence of micropapillary component is associated with more aggressive behavior of salivary duct carcinoma. It is also important for pathologists to recognize that GCDFP-15 and AR expression can be reduced in micropapillary carcinoma in the differential diagnosis of metastatic tumor.     

Lung adenocarcinoma with a micropapillary pattern: a clinicopathological study of 25 cases

Lung adenocarcinoma with a micropapillary pattern has recently been described, but its biological behavior is as yet uncertain. In this article we present a clinicopathological study of lung adenocarcinoma with micropapillary morphology. We selected 25 patients with lung adenocarcinoma with micropapillary morphology from the 2001-2004 pathology files (age range 54 to 81 years; mean 64.5 years). Micropapillary carcinoma is predominantly located at the periphery of the tumor nodule or mass and occurs irrespective of the subtype of the adenocarcinoma. A micropapillary component was seen against a mucinous background in three cases and microcalcifications resembling psammoma bodies were seen in one case. Four cases showed intensive invasive growth such as micropapillary adenocarcinoma of the breast and 21 showed alveolar type morphology with piling-up of the neoplastic cells with or without stromal invasion. Seven of twenty-three (30.4%) showed lymph node metastases at time of operation. Twelve of twenty-five (48%) showed pleural invasion. Regarding clinical outcome, 14 patients were alive without disease, 5 were alive with disease, and 5 died of the lung adenocarcinoma. No significant relationship was found between the extent of the micropapillary component and prognosis. However, the carcinoma seen in the five patients who died showed breast type histology with intensive invasive growth in three cases and alveolar type histology with intensive stromal invasion in two. Lung micropapillary carcinoma of breast type may behave more aggressively than the alveolar type.     

Colorectal adenocarcinoma with micropapillary pattern and its association with lymph node metastasis.

Micropapillary carcinoma has been reported as an aggressive variant of carcinoma in several organs, where it is associated with frequent lymphovascular invasion and poor clinical outcome. This study explored the clinicopathological features of colorectal adenocarcinoma with a micropapillary carcinoma component and compared them with those of conventional colorectal adenocarcinoma. One hundred seventy-eight consecutive cases of surgically resected colorectal carcinomas were studied for tumor size, type, depth of invasion, nodal and distant metastases, tumor stage, and percentage and extent of micropapillary component. Among 178 cases of colorectal carcinoma, 34 (19.1%) cases had a micropapillary component, which ranged from 5 to 60% of the entire tumor. Lymph node metastasis was identified in 25 of 34 (73.5%) carcinomas with micropapillary component, whereas they were detected in 61 of 144 (42.4%) cases without micropapillary component (P=0.001). Lymphovascular invasion was identified more frequently in carcinoma with micropapillary component (41.2%) than carcinoma without micropapillary component (20.1%; P<0.05). Distant metastases occurred in 4 of 34 cases (11.7%) with micropapillary component and in 10 of 144 cases (6.9%) without micropapillary component (P=0.311). Multivariate regression analysis demonstrated that the presence of micropapillary component, as well as tumor stage and lymphovascular invasion are independent predictors of regional nodal metastasis.     

Serous papillary adenocarcinoma of the female genital organs and invasive micropapillary carcinoma of the breast. Are WT1, CA125, and GCDFP-15 useful in differential diagnosis?

Serous papillary adenocarcinoma of the female genital organs and invasive micropapillary carcinoma of the breast have close histologic similarities. Thus, when these cancers occur synchronously or metachronously in the same patient, it is difficult to determine the primary site. We examined 23 serous papillary adenocarcinomas (16 ovarian, 5 endometrial, and 2 peritoneal) and 37 invasive micropapillary carcinomas of the breast (12 pure and 25 mixed types) on immunohistochemical expression of Wilm's tumor antigen-1 (WT1), CA125, and gross cystic disease fluid protein-15 (GCDFP-15), which have been reported to be useful in the differential diagnosis of primary ovarian carcinomas versus metastatic breast cancer to the ovary. The positive rates of WT1, CA125, and GCDFP-15 in serous papillary adenocarcinomas were 78%, 78%, and 0%, respectively, and the corresponding rates in invasive micropapillary carcinomas were 3%, 40%, and 38%. The CA125-positive rate of invasive micropapillary carcinoma was higher than the rate reported for other types of breast carcinomas. We consider CA125 to be not always useful in the differential diagnosis of serous papillary adenocarcinoma and invasive micropapillary carcinoma. Although the positive rate of WT1 was significantly higher in serous papillary adenocarcinoma than in invasive micropapillary carcinoma, WT1 expression in endometrial serous papillary adenocarcinoma was infrequent (20%). WT1 and GCDFP-15 could be useful markers for the differential diagnosis of ovarian and peritoneal serous papillary adenocarcinoma versus breast invasive micropapillary adenocarcinoma. However, the availability of GCDFP-15 is limited because of the low positive rate of GCDFP-15 in invasive micropapillary carcinomas.     

Malignant transformation of sialadenoma papilliferum of the palate: a case report

We report a case of a 79-year-old woman with an unusual salivary gland tumor that developed at the junction between the soft and hard palates. The tumor consisted of sialadenoma papilliferum (SP) with areas of an epithelial–myoepithelial carcinoma (EMC) component and a high-grade carcinoma component. There were also transitional regions among the SP, the EMC and the high-grade carcinoma components. The high-grade carcinoma component, which was similar to invasive micropapillary carcinoma of the breast, infiltrated into the right parapharyngeal space and metastasized to the lungs and cervical vertebrae. The high-grade carcinoma cells were positively immunostained for p53 protein. SP has been considered to be a benign tumor with exceptionally good prognosis, and, to the best of our knowledge, there has never been a confirmed case of malignant SP. This is the first report of SP with a definite malignant component.     

Cytologic diagnosis of pulmonary adenocarcinoma with micropapillary pattern: Does it correlate with the histologic findings?

Micropapillary adenocarcinoma is associated with poor‐prognosis in several organs including the lung. The presence of small tight balls of neoplastic cells devoid of fibrovascular core in cytological preparations (micropapillary tufts) has been described as characteristic of micropapillary adenocarcinoma. In the lung, however, this criterion has not been validated. The cytological material of 46 cases of histologically proven pulmonary adenocarcinoma with a micropapillary component was compared to 33 cases with no micropapillary component to determine the specificity of micropapillary tufts for the histologic diagnosis of micropapillary adenocarcinoma. Other histologic patterns of invasive pulmonary adenocarcinomas (acinar, papillary, and solid) were also compared with patterns of neoplastic cell aggregates in cytological preparations. There were no significant differences in the distribution of micropapillary clusters between the two groups. The positive predictive value for the cytologic diagnosis of a micropapillary component in lung adenocarcinomas was of 64%. Similar findings were observed for other invasive patterns. Therefore, the detection of micropapillary tufts in cytology is not specific for the diagnosis of a pulmonary micropapillary adenocarcinoma in the lung. Diagn. Cytopathol. 2009. © 2009 Wiley‐Liss, Inc.     

Micropapillary variant of transitional cell carcinoma of the ureter

Micropapillary variant of transitional cell carcinoma (TCC) is a rare entity, having a distinct micropapillary component mimicking papillary serous carcinoma of the ovary and has been reported exclusively in the urinary bladder. We experienced a case of micropapillary variant of TCC in the ureter. The tumor showed a predominant proportion of micropapillary component and accompanied a TCC in situ lesion and a high-grade TCC. A metastatic lesion in the regional lymph node also showed an entirely micropapillary pattern. Initially, our case was confused with adenocarcinoma, especially metastatic, because the micropapillary architecture resembled an abortive glandular structure and tumor cell nests were predominantly located in empty spaces mimicking vascular invasion. The patient died with peritoneal metastases 20 months after the initial diagnosis. We report the first case of a micropapillary variant of TCC occurring in the ureter.     

Pleural malignant mesothelioma with invasive micropapillary component and its association with pulmonary metastasis

The micropapillary pattern (characterized by papillary structure with tufts lacking a central fibrovascular core) is a predictor of aggressive carcinoma. The purpose of the present study was to review 34 pleural malignant mesotheliomas (21 epithelioid, five sarcomatoid, seven biphasic and one lymphohistiocytoid), with special reference to the presence of invasive micropapillary component. Two invasive micropapillary pattern‐positive tumors were identified. The invasive micropapillary pattern was seen to have a focal distribution in 15–20% of the tumor tissues. The majority of the invasive micropapillary clusters expressed MUC1 along the outer cell surface. Analysis of pleural malignant mesotheliomas with epithelioid features and with or without invasive micropapillary pattern (21 epithelioid and seven biphasic subtypes) indicated pulmonary micrometastases in only the invasive micropapillary‐positive tumors (P < 0.015), and the spread was probably via the lymphatics. Lymphatic involvement (confirmed on immunohistochemistry with D2‐40 antibody) and lymph node metastasis were found in both of the invasive micropapillary‐positive tumor patients, whereas they were noted in only one of 10 (10%, P < 0.046) and three of nine (30%) invasive micropapillary‐negative patients. To the authors’ knowledge this is the first study to indicate the presence of invasive micropapillary component in pleural malignant mesothelioma. This component can predict more aggressive lymphatic spread, similar to that of carcinomas in other organs with micropapillary pattern.     

A rare case of colorectal micropapillary carcinoma

Micropapillary carcinoma is regarded as an aggressive variant of adenocarcinoma in any location. It is histologically characterized by papillary cell clusters surrounded by clear spaces. The reported proportion of micropapillary carcinoma component in the entire tumor ranges from 5-80% and no pure cases have been reported. To date, there are approximately 130 cases reported in the colorectum. We recently examined a patient with a pure micropapillary carcinoma showing co-expression of CK7, CK20, and absence of CDX2, which had an aggressive tumor with extensive perineural, vascular, and lymphatic invasion as well as extensive nodal metastasis. The presence of a micropapillary carcinoma in the colorectum seemed to be closely related with nodal metastasis, as observed in micropapillary carcinomas from other organs. Thus, if a micropapillary component is identified in a tumor, particularly in a biopsy specimen, extensive surgical resection should be considered due to the high potential for nodal metastasis, even if the preoperative diagnosis is a pedunculated early colorectal cancer.     

Advances in salivary gland pathology

This review summarizes the new findings on salivary gland pathology under the following categories: immunohistochemistry; molecular genetics; newly recognized tumour types; known tumour entities with new findings; and progression of salivary gland tumours. In the application of immunohistochemistry, CD117 can aid in highlighting the luminal cell component of various salivary gland tumours, whereas p63 or maspin can aid in highlighting the abluminal cell component. A high Ki67 index remains the most useful marker to predict adverse outcome in salivary gland carcinoma. Specific chromosomal translocations are recognized in pleomorphic adenoma (with translocation involving PLGA1 or HMGA2 gene) and mucoepidermoid carcinoma (with MECT1-MAML2 gene fusion). Newly recognized entities include: sclerosing polycystic adenosis (with recent molecular evidence supporting its neoplastic nature), sclerosing mucoepidermoid carcinoma with eosinophilia, keratocystoma, adenoma with additional stromal component (lymphadenoma, lipoadenoma and adenofibroma), cribriform adenocarcinoma of the tongue and signet ring adenocarcinoma of minor salivary gland. Known tumour entities with new findings include: salivary duct carcinoma (with newly recognized mucinous, micropapillary and sarcomatoid variants), intraductal carcinoma (with controversies in terminology), mucoepidermoid carcinoma (with newly proposed grading parameters and oncocytic variant), epithelial-myoepithelial carcinoma (with newly recognized morphological variants), small cell carcinoma (with most cases being related to Merkel cell carcinoma), extranodal marginal zone B-cell lymphoma (with specific chromosomal translocation) and chronic sclerosing sialadenitis (being a component of IgG4-related sclerosing disease). Progression of salivary gland tumours can take the form of malignant transformation of a benign tumour, progression from low-grade to high-grade carcinoma, dedifferentiation, or stromal invasion of an in situ carcinoma.     

Breast carcinoma with micropapillary features: clinicopathologic study and long-term follow-up of 100 cases

To study the clinicopathologic characteristics and prognosis of invasive micropapillary carcinoma of breast (IMPC), 100 cases of invasive breast carcinoma with an IMPC component were reviewed. Compared with invasive ductal carcinoma, not otherwise specified, with similar histologic grades, carcinomas with IMPC were larger sized, had a higher lymph node metastasis rate with more nodes involved per case, and exhibited increased lymphovascular invasion. The presence of IMPC strongly correlated with the more aggressive behavior. No significant association was established between the proportion of the IMPC component and overall tumor size, histologic grade, lymph node metastasis rate, and distant metastasis, but a trend was noted. Long-term follow-up demonstrated a poorer 5-year and 10-year survival rate for patients with breast carcinoma containing an IMPC component. Breast carcinomas with micropapillary features are more aggressive tumors with a poorer prognosis. This specific structure should be carefully evaluated in the surgical pathology examination of breast carcinoma specimens.     

Micropapillary urothelial carcinoma of the upper urinary tract: Clinicopathologic study of five cases

We report 5 cases of micropapillary urothelial carcinoma (MPUC) involving the renal pelvis (2), renal pelvis and ureter (2), and proximal ureter (1). The patients were 2 women and 3 men, ages 65 to 92 years (mean, 76.0 years). All tumors showed a high-grade transitional cell carcinoma component, and in 3 cases, there also were areas of in situ carcinoma. The case involving only the ureter occurred in a 65-year-old man with a history of nephrectomy 12 years previously for urothelial carcinoma of the renal pelvis. The tumor recurred in the ureteral stump. In all cases, areas displaying micropapillary architecture were observed. In 2 cases the micropapillary areas were noninvasive; in 1 case a pure invasive pattern was seen; and in 2 cases a mixed invasive and noninvasive pattern was present. the micropapillary pattern was invasive; and the case involving the ureteral stump contained invasive and noninvasive micropapillary carcinoma. All patients died of their tumors from 3 to 24 months after initial diagnosis. MPUC involving the renal pelvis and ureter is associated closely with advanced stages of disease and has highly aggressive behavior. Recognition of this growth pattern is important for prognosis and avoiding misdiagnosis with papillary renal cell carcinoma and other tumors.     

乳腺浸润性微乳头状癌临床病理因素的研究现状

目的 探讨年龄、肿瘤大小、组织学及核分级、腋淋巴结、激素受体、生长因子受体及细胞增值率等临床病理因素在乳腺浸润性微乳头状癌（IMPC）发生、发展、转移及预后的评估中的意义.方法 应用Pubmed及CNKI数据库系统以“IMPC”为关键词检索文献,筛选出相关一次文献,对文献进行分析.结果 IMPC中肿瘤大小、IMPC成分的比例、共存病灶的病理类型和组织学分级均与淋巴结转移的发生率无关;IMPC独特的形态学特征和间质淋巴细胞浸润可能是其高侵袭性的原因所在;IMPC中雌激素受体（ER）和人类表皮生长因子受体2（HER2）阳性表达比率高,其中,ER阳性表达可作为一个积极预后指标.结论 对IMPC这一特殊亚型认识还比较肤浅,随着研究的不断深入,IMPC的诊治状况将得到进一步的改观.     

Invasive micropapillary carcinomas of the ampullo-pancreatobiliary region and their association with tumor-infiltrating neutrophils.

Invasive micropapillary carcinoma, originally described as a distinctive type of invasive carcinoma in the breast, is being increasingly recognized as a separate entity in many other organs; however, it has not yet been documented in the pancreas or periampullary region. In this study, 313 pancreatic and 73 periampullary carcinomas were reviewed to investigate the micropapillary pattern in this location. Eight periampullary and eight pancreatic cases (4%) were composed at least focally (>20%) of invasive micropapillary carcinoma. The patients were 10 males and six females, mean age 69 years. The mean tumor size was 3.2 cm. Lymph node metastasis was detected in 11/15 cases. The median survival was 8 months (all were resected). Invasive micropapillary carcinoma was characterized by small, closely packed micropapillary clusters (without fibrovascular cores) lying within clefts. The cells had moderate degree of nuclear atypia. In nine cases, there was abundant inflammation composed of neutrophils concentrating around the tumor cells, both intraepithelial ('cannibalism') and stromal. Molecules implicated in abnormalities of tumor cell-stroma adhesion, galectin-3 and E-cadherin were expressed in the cytoplasm of 11/11 and 9/11 cases, respectively. Reversal of cell polarity was observed by MUC 1 in all 11 cases tested, which showed labeling in the stroma-facing surfaces of the micropapillary clusters, also confirming that the clefts are not merely a processing artifact, but indeed a true biologic alteration. In conclusion, invasive micropapillary carcinoma constitutes 4% of carcinomas in the pancreatic/periampullary region and is commonly associated with abundant neutrophilic infiltrates. Invasive miropapillary carcinoma appears to be more common in periampullary than in pancreatic invasive micropapillary carcinoma would qualify as poorly differentiated both based on pattern and the median survival (8 months)..     

Cytological features of lung adenocarcinoma with micropapillary pattern in the pleural or pericardial effusion: analysis of 5 cases

Micropapillary pattern is a distinct histopathological pattern, and usually shows a high frequency of lymphatic invasion and lymph node metastases. This pattern is also reported in lung adenocarcinoma, however, only one cytological report of lung adenocarcinoma with micropapillary pattern has been reported. In this study, we analyzed the cytological features of this type of carcinoma in the pleural or pericardial effusion. This study was comprised of 5 consecutive cases of lung adenocarcinoma with micropapillary pattern, in which the tumor cells were present in the pleural or pericardial effusion and whose diagnoses were histopathologically confirmed. The characteristic cytological findings in the pleural or pericardial effusion were as follows: i) tightly cohesive small nests of tumor cells showing papillary structure without fibrovascular core, ii) these nests were comprised of approximately 5-20 tumor cells, iii) cauliflower-like and acinar-like structures were also observed, iv) intracytoplasmic vacuoles were observed in 40% of the cases, and v) the neoplastic cells had large round to oval nuclei containing coarse chromatin and occasional conspicuous nucleoli. It has been reported that the presence of micropapillary structure and intracytoplasmic vacuolation are also characteristic cytological features of micropapillary carcinoma of the urinary bladder, therefore, they are thought to be common cytological features of carcinomas with micropapillary pattern. Consequently, detection of these features can lead to a cytodiagnosis of lung adenocarcinoma with micropapillary pattern in the pleural or pericardial effusion. Recognition of these features is important because this type of tumor shows an aggressive clinical course.     

Micropapillary transitional cell carcinoma of the urinary bladder: report of two cases

Micropapillary carcinoma is an uncommon variant of urothelial carcinoma with apparent high metastatic potential. The reported cases in the literature were associated with high grade and stage of disease at presentation and a poor prognosis. Micropapillary carcinoma is considered a tumor with an aggressive behavior, even though the morphology may be deceptive. The presence of a micropapillary carcinoma component in bladder biopsies should alert the urologists to the potential of higher stage disease and deep biopsies should be obtained. Two cases of micropapillary carcinoma of the urinary bladder were presented. A 71-year-old woman and a 68-year-old man presented with urinary symptoms. Cystoscopy revealed a papillary tumor on the bladder wall in both cases. Pathologic examination of transurethral resection specimen showed an invasive micropapillary carcinoma; small solid nests lying in small clear spaces that were not stained with antibody CD34. Thus, the lacunar histological pattern did not appear to represent invasion of vascular spaces. Only one case showed an association with urothelial carcinoma. No case showed muscle invasion. No recurrence or metastasis were observed after the initial diagnosis in the two cases.     

E-selectin and Sialyl Lewis X expression is associated with lymph node metastasis of invasive micropapillary carcinoma of the breast

To investigate the possible roles of E-selectin and its ligand, Sialyl Lewis X, in lymph node metastasis of invasive micropapillary carcinoma of the breast, 100 cases of invasive micropapillary carcinoma and 97 cases of invasive ductal carcinoma were analyzed immunohistochemically for the expression of E-selectin and Sialyl Lewis X, along with CD34, to measure the microvessel density of invasive micropapillary carcinoma. We found that the number of E-selectin-positive vessels was greater in invasive micropapillary carcinoma than in invasive ductal carcinoma, and it was significantly correlated with the histological grade, the number of positive lymph nodes, and the microvessel density of invasive micropapillary carcinoma. The Sialyl Lewis X expression of invasive micropapillary carcinoma was higher than that of invasive ductal carcinoma, which was also associated with lymph node metastasis. In invasive micropapillary carcinoma, the Sialyl Lewis X expression was predominantly in the stroma-facing surface of the cell clusters and the adjacent stroma, while in invasive ductal carcinoma it was largely intracytoplasmic or intercellular. These findings suggested that E-selectin and Sialyl Lewis X might play an important role in lymph node metastasis in invasive micropapillary carcinoma. The expression pattern of Sialyl Lewis X in invasive micropapillary carcinoma suggested that the reversal of cell polarity of invasive micropapillary carcinoma might be as an important factor for the morphogenesis and possibly the pathogenesis, especially their higher rates of lymph node metastasis.