Cacinoma with micropapillary morphology: Clinical significance and current moncepts
Invasive micropapillary carcinoma has been recently recognized as a rare but distinctive variant of carcinoma in various anatomic sites, including breast, urinary bladder, lung, and major salivary glands. Morphologically, it is characterized by small tight clusters of neoplastic cells floating in clear spaces resembling lymphatic channels. Most often this growth pattern is mixed with a variable component of conventional carcinoma or other variants. In addition to a unique morphology, tumors with invasive micropapillary growth share a high propensity for lymphovascular invasion and lymph node metastases. Patients have typically high-stage disease at presentation and a poor clinical outcome compared with that of patients with conventional carcinoma arising in the same organ site. In this article the author reviews the available literature on tumors displaying a micropapillary component.
[Show abstract] [Hide abstract] ABSTRACT: Little is known about mutational landscape of rare breast cancer (BC) subtypes. The aim of the study was to apply next generation sequencing to three different subtypes of rare BCs in order to identify new genes related to cancer progression. We performed whole exome and targeted sequencing of 29 micropapillary, 23 metaplastic, and 27 pleomorphic lobular BCs. Micropapillary BCs exhibit a profile comparable to common BCs: PIK3CA, TP53, GATA3, and MAP2K4 were the most frequently mutated genes. Metaplastic BCs presented a high frequency of TP53 (78 %) and PIK3CA (48 %) mutations and were recurrently mutated on KDM6A (13 %), a gene involved in histone demethylation. Pleomorphic lobular carcinoma exhibited high mutation rate of PIK3CA (30 %), TP53 (22 %), and CDH1 (41 %) and also presented mutations in PYGM, a gene involved in glycogen metabolism, in 8 out of 27 samples (30 %). Further analyses of publicly available datasets showed that PYGM is dramatically underexpressed in common cancers as compared to normal tissues and that low expression in tumors is correlated with poor relapse-free survival. Immunohistochemical staining on formalin-fixed paraffin-embedded tissues available in our cohort of patients confirmed higher PYGM expression in normal breast tissue compared to equivalent tumoral zone. Next generation sequencing methods applied on rare cancer subtypes can serve as a useful tool in order to uncover new potential therapeutic targets. Sequencing of pleomorphic lobular carcinoma identified a high rate of alterations in PYGM. These findings emphasize the role of glycogen metabolism in cancer progression.0Comments 0Citations
- "Micropapillary BCs (*6 % of all BCs) are characterized by clear retraction-like spaces containing clusters of tumor cells organized in nests or tubules, without fibrovascular cores. They are associated with higher incidence of lymphovascular invasion and nodal metastases than common invasive ductal carcinomas  . Metaplastic BCs (1 % of all BCs) are characterized by the concomitant presence of adenocarcinomatous and metaplastic elements (epithelial, mesenchymal, or both) . "
[Show abstract] [Hide abstract] ABSTRACT: Background Breast metastasis from extramammary malignancy is uncommon and often presents diagnostic challenges. Herein, we report a case of a patient with metachronous isolated breast metastasis from pulmonary adenocarcinoma with micropapillary component. Case presentation A 47-year-old woman presented with left breast nodule detected on a screening breast ultrasonography. She had surgery for pulmonary adenocarcinoma 3 years ago, and was disease-free state in the follow up studies. The patient was diagnosed with invasive micropapillary carcinoma of the breast by core needle biopsy. She underwent left breast lumpectomy and sentinel lymph node biopsy, and the histologic findings revealed micropapillary carcinoma. Based on the immunohistochemical study, the final diagnosis was solitary breast metastasis from pulmonary adenocarcinoma with micropapillary component. Conclusions The diagnosis of metastasis to the breast from extramammary malignancies is difficult but important for proper management and prediction of prognosis. A careful clinical history with a thorough clinical examination is needed to make the correct diagnosis.0Comments 0Citations
- "Invasive micropapillary carcinomas have been described in several organs including urinary bladder, lung, major salivary glands, ovary and breast . Adenocarcinoma with micropapillary component is a morphologic variant of carcinoma and usually recognized as a poor prognostic predictors . We report a case of metachronous isolated breast metastasis from pulmonary adenocarcinoma with micropapillary component which was initially favored to be primary breast cancer. "
[Show abstract] [Hide abstract] ABSTRACT: Recent reports indicate that papillary thyroid carcinoma with hobnail features, also designated as micropapillary variant of papillary thyroid carcinoma, is a rare but very aggressive variant of papillary thyroid carcinoma. We examined the histopathologic and immunohistochemical features of 24 cases of papillary thyroid carcinoma with hobnail/micropapillary component to determine the prognostic significance of the amount of hobnail/micropapillary features in these tumors. The patients included 18 women and 6 men. Ages ranged from 28 to 78 years (mean, 57 years). Tumor size ranged from 1 to 5.8 cm (mean, 3 cm). The average follow-up time was 106 months (range, 4-274 months). Twelve cases (50%) of papillary thyroid carcinoma showed more than 30% hobnail/micropapillary features, and all but 3 cases were associated with an aggressive behavior. During the follow-up, 6 of these patients died of disease after a mean of 44.8 months, and 3 patients remained alive with extensive disease after a mean follow-up of 32.3 months. Metastases to lymph nodes or distant organs showed a hobnail pattern of growth similar to the primary tumor. The remaining 3 patients with prominent hobnail/micropapillary features were alive with no evidence of disease after a mean follow-up of 125.3 months. The other 12 papillary thyroid carcinoma cases (50%) showed less than 30% hobnail/micropapillary features. Nine of these patients were alive without disease after a mean of 162 months, and 1 patient died of sepsis, which was not related to thyroid tumor after 155 months. Two patients in this group died of disease after 21 and 163 months, respectively. These findings confirm earlier observations that papillary thyroid carcinoma with hobnail/micropapillary features is an aggressive variant of papillary thyroid carcinoma. Tumors with more than 30% hobnail/micropapillary features were often very aggressive, although 2 patients with tumors with 10% hobnail/micropapillary features also had poor outcomes.0Comments 19Citations
- "The inverted polarity of the cells that compose the micropapillary nests with an inside-out growth pattern , which has been shown by immunohistochemical and ultrastructural studies [15,16], seems to be most likely related to the high invasive potential and drug resistance of these tumors specially in breast carcinoma . The histologic micropapillary carcinoma profile described in other studies [8,10,18] was characterized by small pseudopapillary clusters of cancer cells with inverted cell polarity, which was also confirmed immunohistochemically by the membranous staining pattern of MUC1 (clone MA695), toward the stromal pole only, in the tumor cell clusters. In the present case series of hobnail/micropapillary variant of PTC, the hobnail cells showed increased N/C ratios, moderately to highly pleomorphic nuclei located in the middle or apex of cytoplasm, and abundant cytoplasm with eosinophilia. "