Faculty Bibliography

Thanatosomes, a form of degenerative intracellular hyaline globules, have been described in various neoplastic and nonneoplastic disease processes in several organs. These structures are indicative of apoptotic cell death. Herein, we report 2 cases of malignant phylloides tumor, both of which showed numerous thanatosomes-to the point of dominating the histological appearance and masking the stromal element. Our subsequently conducted study showed that thanatosomes were present in 14 of 86 (16.3%) high-grade malignant breast tumors. The structures were identified in 5/25 (20%) malignant phylloides tumors, 4/19 (21.1%) metaplastic spindle cell carcinomas, 3/21 (14.3%) invasive carcinomas s/p neoadjuvant chemotherapy, and 2/21 (9.5%) poorly differentiated invasive ductal carcinomas. When present, thanatosomes were typically a rare and focal finding in most types of cases. In malignant phylloides tumors, the structures were relatively more numerous when present. Our study shows that although thanatosomes can be present in several types of malignant breast tumors, they are more common in malignant phylloides tumor. Only rarely, as evident from our 2 index cases, do thanatosomes cause diagnostic difficulty.

Breast cancer patients who receive radiation therapy or develop chronic lymphedema following axillary dissection can develop secondary mammary angiosarcomas (ASs) and, additionally, atypical vascular lesions (AVLs) in the former group. Recently, MYC amplification by fluorescence in situ hybridization (FISH) has been identified in secondary mammary AS but not in AVL and most primary mammary AS as well as AS of other sites. We studied MYC amplification and MYC protein expression in 7 radiation-induced AVLs, 9 secondary mammary ASs, 17 primary mammary ASs, and 20 primary ASs of other sites by FISH analysis and immunohistochemistry. All 9 secondary mammary ASs showed gene amplification and protein expression, whereas neither was found in any of 7 AVLs. No MYC amplification or protein expression was identified in any of the 17 primary mammary ASs. Among primary ASs of other sites, 1 cardiac AS and 1 skin AS showed gene amplification and protein expression. The remaining 18 did not show amplification (90%), but some demonstrated protein expression (39%). We conclude that MYC amplification by FISH is present in secondary mammary AS but not in AVL. We also found MYC amplification in 1 primary skin AS and 1 primary cardiac AS. There was 100% concordance between MYC amplification and protein expression in all AVL, primary mammary AS, and secondary mammary AS, whereas only 65% concordance was found in AS of other sites. MYC protein expression in AS can be helpful in certain diagnostic scenarios in the breast but not in other sites.

MRI of the breast is an increasingly employed modality for breast imaging due to its relatively high sensitivity for the detection of breast carcinoma. Cumulative data indicate that MRI of the breast has relatively higher sensitivity, but lower specificity than mammography. However, data regarding the diagnostic yield for particular types of breast lesions detected via breast MRI remain scant. Over a 3.5-year period, we evaluated histological findings of 192 needle core biopsies of MRI detected breast lesions. In this series, the positive predictive value of MRI detected lesions for breast carcinoma was 20%. Invasive carcinoma was diagnosed in 16/192 (8%) and in situ carcinoma in 22/192 (11%). The most commonly detected histological finding was cystic apocrine hyperplasia (19%), a benign entity.

Cystic hypersecretory carcinoma (CHC) is an uncommon variant of ductal carcinoma in situ characterized by, among other features, the presence of luminal secretion resembling thyroidal colloid. CHC is thought to behave in an indolent manner but has the potential to give rise to invasive carcinoma, which is often poorly differentiated. We studied the immunohistochemical, clinical, and morphologic features of 10 cases of CHC. All patients were women averaging 62.8 years in age (range, 47 to 79 y). The clinical/radiographic presentation was a mass (5/10), calcifications (3/10), bloody nipple discharge (1/10), and unknown (1/10). Microscopic size of CHC ranged from 0.2 to 2.7 cm (mean, 0.9 cm). Micropapillary growth was present in all cases. Nuclear grade was intermediate (5/10) or high (5/10). One case also showed microinvasive carcinoma. All cases arose in a background of cystic hypersecretory hyperplasia (CHH) and/or CHH with atypia. CHC was ER in 8/10 cases (ER+/PR+, 4/10; ER+/PR+, 4/10). Two cases were ER-/PR-, including the case with microinvasive carcinoma. All were HER2-. Androgen receptor was expressed in 3/10 (30%) cases. Myoepithelial stains p63, smooth muscle myosin, and CK5 showed circumferential staining in 9/10 (90%) cases, whereas 1 case was negative for p63, smooth muscle myosin, and CK5 in both CHC and adjacent CHH. Basal-like carcinoma markers EGFR, CK14, and CK5 were negative in all cases, with the exception of 1 case that was positive for EGFR. Four patients with follow-up information showed no evidence of disease (mean, 5.5 y). CHC is a distinct variant of ductal carcinoma in situ that arises in a background of CHH and is characterized by micropapillary growth, intermediate-grade to high-grade nuclei, and luminal colloid-like secretion. CHC is usually ER and HER2-. Negative or discontinuous reactivity with myoepithelial markers may be seen, despite its in situ nature. CHC usually behaves in a nonaggressive manner as was seen in our patients who were all free from disease at last follow-up.

BACKGROUND:Pancreatic cancer is an aggressive disease which metastasizes readily. The presence of brain metastases from pancreatic cancer is rare and it carries a poor prognosis. Our approach to treating these lesions stresses extensive use of stereotactic radiosurgery (SRS), whereas other reports focus on surgical resection. CASE REPORT/METHODS:Information regarding the patient's clinical history was extracted from a retrospective review of the medical records and imaging studies. The patient survived seven years after his primary diagnosis of pancreatic cancer, and 36 months after diagnosis of metastatic disease to the brain. In addition to surgical resection and the use of multiple chemotherapeutic agents, the patient received six separate radiosurgery treatments. CONCLUSION/CONCLUSIONS:We present a case of brain metastasis from pancreatic cancer that is remarkable for an unusually long survivorship and discuss the utility of SRS along with a multimodality treatment approach for dealing with these cases.