Faculty Bibliography

OBJECTIVE: While an echogenic intracardiac focus (EIF) is associated with an increased risk of trisomy 21 (T21), the magnitude of that risk remains controversial, particularly in the setting of a low-risk triple screen (TS). The objective of this study is to define the risk of T21 in patients with a low-risk TS and an isolated EIF. STUDY DESIGN: A retrospective analysis was performed on patients presenting prior to 22 6/7 weeks of gestation. Patients met criteria for inclusion if an EIF was noted, a TS had been drawn, the anatomic survey was complete and was determined to be normal, and karyotyping or delivery occurred at Bellevue Hospital. A high-risk TS was defined as a risk of <1:500, assuming a 2-fold increased risk in the setting of an isolated EIF. A low-risk TS was defined as a risk of >1:500. Statistical analysis was performed using chi-square, with p values of <0.05 considered significant. RESULTS: 7,318 anatomic surveys were performed. An EIF was identified in 584 patients (7.98%), of which 391 met the criteria for inclusion. Of the 391, 51% were Asian and 38% were Hispanic; 348 had a low-risk TS and 43 had a high-risk TS. Patients with an EIF and a low-risk TS had a significantly lower risk of having a T21 pregnancy compared to those with a high-risk TS and an EIF (0 vs. 2.3%; p = 0.004). CONCLUSION: An isolated EIF with a low risk TS is not associated with an increased risk of T21

CONTEXT: Medullary carcinoma (MC) is a special type of breast cancer that has a better prognosis than atypical medullary carcinoma (AMC) and high-grade invasive ductal carcinoma (HGIDC) with prominent lymphocytic infiltrates. What accounts for the different clinical courses of these carcinomas, despite their similar histology, is unknown. To address this issue, we performed a comparative study of amplification and overexpression of HER-2/neu and expression of several other important biochemical markers (p53, MIB1, and estrogen receptor [ER]/progesterone receptor [PR]) in these 3 cancer groups. OBJECTIVE: To evaluate HER-2/neu, p53, MIB1, and ER/PR as markers in the differential diagnosis of MC, AMC, and HGIDC.Design.-Nine cases of MC, 13 cases of AMC, and 16 cases of HGIDC with prominent lymphocytic infiltrates were identified according to strict histologic criteria. All tests were performed on formalin-fixed, paraffin-embedded archival tissues. HER-2/neu gene amplification was examined by fluorescence in situ hybridization using PathVysion HER-2 DNA probes. Expression of HER-2/neu, p53, MIB1, and ER/PR was detected by immunohistochemistry. chi2 and Student t tests were applied for statistical analyses. RESULTS: None of 9 cases of MC examined had either amplification or overexpression of HER-2/neu (0%). In contrast, HER-2/neu amplification was observed in AMC (46%, P <.025) and HGIDC (56%, P <.005). All 3 categories of tumors had similar percentages of expression of p53 (78% of MC, 77% of AMC, and 69% of HGIDC) and MIB1 (89% of MC, 92% of AMC, and 94% of HGIDC). Immunostaining for ER/PR was rarely positive in either MC or AMC, and there were no significant differences of expression of ER/PR between these 2 lesions (P >.05). However, the expression rate of ER/PR (31%/44%) in HGIDC is higher than in both MC (P =.05) and AMC (P =.01). CONCLUSIONS: Medullary carcinoma of breast is distinct from AMC and HGIDC with prominent lymphocytic infiltrates in amplification and overexpression of HER-2/neu. This difference may account for its different clinical and biological behavior, and may potentially aid in diagnosis and management of these groups of patients

We report the findings from an aspiration biopsy and resection of a chordoma-like tumorous mass in the wall of the thorax of a 36-yr-old man with immunohistochemical, ultrastructural, and cytogenetic studies. The 4-cm oval tumor was an incidental finding on physical examination, and no other lesions were identified after comprehensive radiologic studies. The aspirate was composed of sheets and nests of cells with distinct borders in a myxoid and fibrillary extracellular matrix. The neoplastic cells were uniform and round or polygonal with abundant pale blue vacuolated cytoplasm and small round, central or eccentric nuclei. On electron microscopy, mitochondrial rough endoplasmic reticulum complexes were seen in neoplastic cells. These features were similar to those of a conventional chordoma. However, the cytogenetic pattern, 43, XY ,-1, -2, der (5)t(1p;5q), -6, add(8p) ,add(10q), was not typical. In addition, the neoplastic cells were positive for vimentin, S-100, AE1/AE3, CAM 5.2, and CK 19; were focally positive for EMA and smooth muscle actin; and were negative for cytokeratin 1 and 10 (34 beta E12), CK 7, CK 8 (35H 11B), CK 17, and CK 20. The cytogenetic and immunohistochemical patterns were different from conventional chordoma and its peripheral counterpart, chordoma periphericum, suggesting the diagnosis of parachordoma. To the best of our knowledge, this is the first report of fine-needle aspiration of this newly defined and rare entity

Seckel syndrome is a rare autosomal recessive disorder with characteristic craniofacial dysmorphism, skeletal defects, mental and prenatal growth retardation. About 50 cases have been reported in the literature. Hematologic abnormalities with associated chromosomal fragility have been noted in about 15% of the reported cases. We report a patient with Seckel syndrome with myelodysplastic features and clonal T-cells in the bone marrow but no evidence of chromosomal fragility. After 5 years of follow-up, this patient remains asymptomatic without any treatment and with stable peripheral blood counts

Gastrointestinal stromal tumor (GIST), a stromal tumor of the gastrointestinal tract defined as CD117 (c-kit)-positive neoplasm, occurs primarily in adults. GIST with CD117 (c-kit) mutation and certain cytogenetic abnormalities is associated with malignancy, though a definite relationship between prognosis and molecular alterations remains to be elucidated. We report the cytologic features of an epithelioid GIST arising in the stomach of a child and metastatic to the liver, and the molecular mutational analysis of both the primary gastric tumor and the liver metastasis. Literature of pediatric GISTs was also reviewed. Fine needle aspiration of the liver metastasis, processed by Ultrafast Papanicolaou stain, showed fragments of cohesive small epithelioid cells with bland oval nuclei and unipolar cytoplasm transected by capillaries. Immunohistochemically, all nodules in the stomach and liver expressed CD117 (c-kit). Interestingly, some of the gastric tumor clusters were uniformly CD34 positive, whereas others were uniformly CD34 negative, suggesting heterogeneity of tumor clones. The presence of neurosecretory granules further subtyped the tumor into gastric autonomic nerve tumor (GANT). Molecular mutational analysis, performed in both the gastric tumor and the liver metastasis, showed no sequence abnormality in exons 9, 11, and 13 of CD117 (c-kit). Cytogenetic study revealed normal karyotype. These features might suggest a different molecular mechanism leading to malignancy in certain GISTs arising in children

The fine-needle aspiration cytologic findings of Wilms' tumor occurring in a 20-yr-old female patient and a 35-yr-old male patient showing blastemal, spindled sarcomatous and rare epithelial components are reported. The male patient had the typical presentation of renal mass with metastasis to lung and pleura, whereas the female patient had an unusual presentation with the tumor originated from the subcapsular nephrogenic zone of the kidney, extending into the liver without invasion into the renal cortex. Cytogenetic analysis of this case identified: 90, XXXX, +2x3-4, -5, -15, -16, -17, -17, i (17)(q10) x2. This finding may represent a genetic change associated with Wilms' tumor of older pediatric and young adult patients. To the best of our knowledge, this case is the sixth case with cytogenetic study and the first case revealing isochromosome 17q of an adult Wilms' tumor

Amplification of Her-2/neu in breast carcinoma is associated with poor prognosis, short disease-free interval, and short survival time in both node-negative and -positive patients. Little is known about the starting point of amplification of Her-2/neu and how it progresses from benign to malignant breast lesions. We attempted to address these questions by evaluating amplification of Her-2/neu in benign, premalignant, and malignant lesions using fluorescence in situ hybridization (FISH). Twenty-six patients with Her-2/neu-overexpressing invasive ductal carcinomas (as judged by strong immunoreactivity with Her-2/neu antibody) and coexisting lesions of ductal hyperplasia (DH), atypical ductal hyperplasia (ADH), ductal carcinoma in situ (DCIS) in the vicinity of the invasive tumor (as judged by review of the hematoxylin and eosin-stained sections), as well as metastatic carcinoma in axillary lymph nodes (mets) were selected for this study. In the primary carcinomas, a close relationship was present between overexpression as detected by immunohistochemistry (IHC) and amplification as demonstrated by FISH (85% concordance). Among these patients, amplification of Her-2/neu in ADH was demonstrated in 7 of 13 cases with ADH, and in DCIS, in 21 of 22 cases with DCIS. There was no amplification in DH or normal ductal epithelium. Significantly, in all 12 patients with synchronous positive axillary lymph nodes, there was concordant amplification of Her-2/neu in the primary and metastatic carcinoma. Amplification was consistent in multifocal metastases, despite morphological heterogeneity in some patients. Amplification ratios increased from ADH to DCIS to invasive carcinoma (P <.01, ADH versus DCIS; P <.05, DCIS versus invasive cancer), but there was no difference in amplification ratios between primary cancers and synchronous axillary metastases (P >.05). We also evaluated Her-2/neu amplification in 21 patients without Her-2/neu overexpression in their primary carcinomas (as judged by absent immunoreactivity with Her-2/neu antibody). Three showed amplification in both primary and metastatic lesions, with a low amplification ratio (approximately 2). One patient had amplification in the primary tumor but not in an axillary metastasis. Two patients exhibited slight amplification in the metastatic carcinoma (ratios 1.6 and 2), but not in their primary cancers. This FISH study indicates that amplification of Her-2/neu can emerge de novo in any stage of the disease process, from ADH to metastatic lesions, but most often appears first in ADH or DCIS. The degree of Her-2/neu amplification increases with progression to invasive carcinoma, there being no further increase in synchronous metastasis. Our data suggest that amplification of Her-2/neu appears to be mainly involved in initiation of breast oncogenesis and that its role in progression of breast cancers is uncertain