Venetia Sarode

Autopsy findings and clinical diagnoses: A review of 1,000 cases

The protocols of 1,000 consecutive adult patients autopsied during the period June 1983 to December 1988 were retrospectively analyzed and the findings were compared with clinical diagnoses. The autopsy rates during this period ranged between 23% and 27% of hospital deaths. Eighty-seven percent of the autopsied patients were between 15 and 59 years of age. Major discrepancies between the autopsy reports and the clinical diagnoses were present in 31.7% of all autopsy reports reviewed. Infectious diseases were the most common cause of death (46.8%), followed by cardiovascular diseases (17.1%) and neoplastic diseases (14.3%). Infections were clinically recognized in 66.7% of cases and were missed or found to be incorrect in 33.3% of cases. Tuberculosis comprised 33.8% of the major bacterial infections and was clinically diagnosed in 82% of cases. Eighty-nine percent of the major fungal infections were not suspected clinically. Rheumatic heart disease (43.8%) was the most common cardiovascular disorder and was clinically diagnosed in 93.3% of cases. Pulmonary vascular episodes were the least common cause of death and were not suspected clinically in 62.9% of cases. Malignancies were incorrectly diagnosed in 25.8% of cases. We conclude from this study that routine autopsies revealed major unexpected findings that are of clinical importance, and that a continued emphasis on autopsy evaluation is necessary for the improvement of the quality of patient care.

Evidence for the neoplastic transformation of Von-Meyenburg complexes

Von-Meyenburg complexes (VMC) are seen frequently in the liver and are largely considered to be innocuous, with only 11 cases reported in the literature of neoplastic transformation of VMCs. The authors report three cases of cholangiocarcinoma, each occurring in a background of fibrosis and nodularity that was reported initially as micronodular cirrhosis. Although the livers showed cirrhosis, the central veins were often preserved, and regenerative activity was patchy and focal. Histologic examination revealed many VMCs, and a gradual transition from VMCs to hyperplastic or adenomatous lesions and cholangiocarcinoma. The adenomatous lesions consisted of extensive replacement of the parenchyma by tumor-like nodules of ductular proliferations without obvious features of malignancy. All three patients were older than 60 years of age and had portal hypertension. Computed tomographic scans showed multiple, small renal cysts in one patient. Immunohistochemical staining showed positivity for epithelial membrane antigen, carcinoembryonic antigen, and keratins (AE1/AE3 and CAM5.2) in tumor cells, consistent with cholangiocarcinoma. The pattern of fibrosis and nodularity in these cases is not typical of either congenital hepatic fibrosis or usual cirrhosis. The authors propose that these patients represent another aspect in the spectrum of ductal plate malformations that may be modified by other factors such as alcohol, drugs, or infection. To their knowledge, neoplastic transformation of VMCs in the background of such changes has never been reported before.

Tumour biomarker expression relative to age and molecular subtypes of invasive breast cancer.

Background:Quantitative differences in biomarker expression relative to age and molecular subtypes have not been well documented in invasive breast cancer (IBCA).Methods:Oestrogen receptor (ER), progesterone receptor (PR), HER2, ki67, p53 and DNA ploidy was performed by image analysis in 162 consecutive IBCAs in women (⩽40 years) and compared with women ⩾50 years (100 cases). Molecular subtypes were defined by immunohistochemistry (IHC).Results:Among young women, tumours were frequently ER negative (P=0.01) with lower ER (P<0.00), PR (P=0.03), higher ki67 index (KI) (P=0.01) and p53 (P=0.00) compared with older women. Triple negative was more frequent among young women with frequent lymph node involvement compared with older women. Luminal B among young vs old women showed lower ER (67% vs 88%), PR (32% vs 52%), higher KI (48% vs 34%) and p53 (19% vs 7%). Linear regression model showed increasing KI (P<0.0001) and p53 (P=0.0003) according to the molecular subtypes. Survival difference among subtypes was demonstrated by multivariate analysis (P=0.0092) after adjusting for age, race, tumour size, grade and stage.Conclusion:We demonstrated significant differences in biomarker expression relative to age and molecular subtypes. Molecular subtype defined by IHC was an independent prognostic factor.

Experience with Seed Localization for Nonpalpable Breast Lesions in a Public Health Care System

BackgroundSeed localization uses a radioactive source to identify nonpalpable breast lesions for excision; it is an emerging alternative to wire localization (WL). Previous single health system studies report decreased rates of re-excision and improved patient convenience with this technique. This study is the first to implement this procedure in a public health care delivery system composed of a primarily minority and low-income population.Materials and MethodsA multidisciplinary team was formed to create a protocol for breast seed localization (BSL) and monitor the results. After 50 seed localizations were successfully completed, a retrospective matched-pair analysis with patients who had undergone WL during the same period was performed.ResultsOverall experience with the BSL protocol is reviewed, along with the occurrence of a seed loss. Processes necessary to reactivate the BSL protocol and prevent future losses are delineated. BSL is associated with decreased rates of re-excision and can be successfully implemented in a public health care system.ConclusionsBSL is an attractive alternative to WL in a high-volume, county-based population. It allows increased efficiency in the operating room and has a low rate of complications. Cautionary measures must be taken to ensure proper seed chain of custody to prevent seed loss.

Predictors of Invasion and Axillary Lymph Node Metastasis in Patients with a Core Biopsy Diagnosis of Ductal Carcinoma In Situ: An Analysis of 255 Cases

Abstract:  The diagnosis of ductal carcinoma in situ (DCIS) using core biopsy does not ensure the absence of invasion on final excision. We performed a retrospective analysis of 255 patients with DCIS who had subsequent excision. Clinical, radiologic, and pathologic findings were correlated with risk of invasion and sentinel lymph node (SLN) metastasis. Of 255 patients with DCIS, 199 had definitive surgery and 52 (26%) had invasive ductal carcinoma (IDC) on final excision. Extent of abnormal microcalcification on mammography, and presence of a radiologic/palpable mass and solid type of DCIS were significantly associated with invasion on final excision. Sentinel lymph node biopsy was performed in 131 (65.8%) patients of whom 18 (13.4%) had metastasis. Size of IDC and extent of DCIS on final pathology were significantly associated with positive SLN. Micrometastasis and isolated tumor cells comprised majority (71.4%) of the metastases in DCIS. SLN biopsy should be considered in those with high risk DCIS.

Decreased Androgen Receptor Expression Is Associated With Distant Metastases in Patients With Androgen Receptor-Expressing Triple-Negative Breast Carcinoma

To characterize prognostic values of androgen receptor (AR) in triple-negative (TN) breast cancers, we investigated AR expression status and levels, explored an association of AR expression with metastatic disease, and correlated AR expression with Ki-67 in TN invasive breast carcinomas. AR expression was analyzed with immunohistochemistry in 121 cases of TN tumors. Thirty-nine cases had distant metastatic disease and 82 had locoregional disease only. AR was positive in 38 (31.4%) of the 121 cases. Our results indicate that among the AR-positive TN tumors, distant metastases are significantly associated with lower expression of AR compared with cases with only locoregional disease, and that AR expression negatively correlates with Ki-67 expression. These findings suggest that decreased intratumoral AR expression may be predictive of distant metastatic disease and AR expression levels may have potential prognostic value in AR-expressing TN tumors.

Intratumoral Expression Level of Epidermal Growth Factor Receptor and Cytokeratin 5/6 Is Significantly Associated With Nodal and Distant Metastases in Patients With Basal-like Triple-Negative Breast Carcinoma

Triple-negative (TN) breast carcinoma, characterized by estrogen receptor, progesterone receptor, and HER2 negativity, is a group of aggressive tumors that can be further classified into 2 subtypes: basal-like, defined as CK5/6 and/or epidermal growth factor receptor (EGFR) positive by immunohistochemistry; and non-basal-like. Clinical characteristics and tumor profiles were analyzed in 105 cases of TN tumors. Among these cases, 35 had distant metastasis, 34 had axillary nodal metastasis only, and 36 were nodal negative. Our results indicate basal-like TN breast tumors with nodal and distant metastases are significantly associated with a higher intratumoral expression of EGFR and CK5/6 compared to those in the nodal negative group. High level of intratumoral EGFR and CK5/6 expression may play a role in development of nodal or distant metastases in patients with basal-like TN tumors and may be predictive of metastatic disease. Furthermore, EGFR targeted therapy may be potentially useful in the treatment of basal-like TN breast cancer.

Significance of cytologically normal endometrial cells in cervical smears from postmenopausal women

OBJECTIVE To determine the significance of cytologically normal endometrial cells in cervicovaginal (CV) smears from postmenopausal women over age 55 years. STUDY DESIGN From January 1995 to January 1998, 220 women had CV smears demonstrating cytologically normal endometrial cells. The menopausal status, hormone replacement therapy (HRT) and information related to subsequent CV smears and endometrial sampling within 12 months of the initial diagnosis was recorded. RESULTS Eighty-one of the 220 cases (36.8%) had histologic sampling of the endometrium. Thirty-four of 81 (42%) showed no endometrial pathology. Endometrial pathology was identified in 28 of 81 (34%), of which 19 were endometrial polyps (23.4%), 4 were endometrial hyperplasia (4.9%), 4 were endometrial carcinoma (4.9%) and 1 was a leiomyoma (1.2%). Nineteen (23.4%) were insufficient for diagnosis. Ninety-one of 220 women were on HRT, and 129 were not. In the group without HRT, endometrial disease was identified in 22/51 (43%) cases as compared to 6/30 (20%) in the group with HRT (P < .001). Endometrial carcinoma was identified in three (5.8%) cases and one (3.3%) case without and with HRT, respectively. CONCLUSION Although the finding of normal endometrial cells in Pap smears from postmenopausal women was without any clinical significance in the majority of women in this study, in a small number it was associated with endometrial hyperplasia and carcinoma. Women who were not on HRT had a higher incidence of endometrial pathology.

Autocrine VEGF Signaling Promotes Proliferation of Neoplastic Barrett's Epithelial Cells Through a PLC-Dependent Pathway

BACKGROUND & AIMS Tumor cells express vascular endothelial growth factor (VEGF), which induces angiogenesis. VEGF also activates VEGF receptors (VEGFRs) on or within tumor cells to promote their proliferation in an autocrine fashion. We studied the mechanisms of autocrine VEGF signaling in Barretts esophagus cells. METHODS Using Barretts epithelial cell lines, we measured VEGF and VEGFR messenger RNA and protein, and studied the effects of VEGF signaling on cell proliferation and VEGF secretion. We studied the effects of inhibiting factors in this pathway on levels of phosphorylated phospholipase Cγ1 (PLCG1), protein kinase C, and extracellular signal-regulated kinases (ERK)1/2. We performed immunohistochemical analysis of phosphorylated VEGFR2 on esophageal adenocarcinoma tissues. We studied effects of sunitinib, a VEGFR2 inhibitor, on proliferation of neoplastic cells and growth of xenograft tumors in mice. RESULTS Neoplastic and non-neoplastic Barretts cells expressed VEGF and VEGFR2 messenger RNA and protein, with higher levels in neoplastic cells. Incubation with recombinant human VEGF significantly increased secretion of VEGF protein and cell number; knockdown of PLCG1 markedly reduced the recombinant human VEGF-stimulated increase in levels of phosphorylated PLCG1 and phosphorylated ERK1/2 in neoplastic cells. Esophageal adenocarcinoma tissues showed immunostaining for phosphorylated VEGFR2. Sunitinib inhibited VEGF signaling in neoplastic cells and reduced weight and volume of xenograft tumors in mice. CONCLUSIONS Neoplastic and non-neoplastic Barretts epithelial cells have autocrine VEGF signaling. In neoplastic Barretts cells, VEGF activation of VEGFR2 initiates a PLCG1-protein kinase C-ERK pathway that promotes proliferation and is self-sustaining (by causing more VEGF production). Strategies to reduce autocrine VEGF signaling (eg, with sunitinib) might be used to prevent or treat cancer in patients with Barretts esophagus.

Interdigitating dendritic cell sarcoma of the parotid gland: case report and literature review

Interdigitating dendritic cell sarcoma (IDCS) is an exceedingly rare neoplasm arising from the antigen-presenting cells of the immune system. We report a case of IDCS occurring in a 69-year-old man who presented to an outside institution with a painless mass in his right parotid gland for several months. He presented to our institution after undergoing a superficial parotidectomy. A diagnosis of undifferentiated neoplasm, favoring poorly differentiated carcinoma, was made at that time. He underwent a total parotidectomy and neck dissection at our institution. Microscopically, the tumor was composed of atypical spindle cells involving the parotid gland and an ipsilateral level III lymph node. Immunophenotypic analysis demonstrated positive staining for S100, fascin, vimentin, and HLA-II. Follicular dendritic cell, lymphoid, epithelial, myoepithelial, and melanoma markers were negative. Taken together, the above features were consistent with IDCS. An IDCS of the parotid gland is extremely rare, with only 2 cases reported in the literature. The unusual location and morphological similarity to follicular dendritic sarcoma and other types of soft tissue sarcomas can be a diagnostic challenge. Awareness of this tumor and the use of appropriate markers are crucial in making the diagnosis. The patient did well postoperatively, and he underwent a complete course of postoperative irradiation to the right parotid and neck.