Factors affecting the concordance of radiologic and pathologic tumor size in breast carcinoma.

BACKGROUND: Radiologic assessment of tumor size is an integral part of the work-up for breast carcinoma. With improved radiologic equipment, surgical decision relies profoundly upon radiologic/clinical stage. We wanted to see the concordance between radiologic and pathologic tumor size to infer how accurate radiologic/clinical staging is. MATERIALS AND METHODS: The surgical pathology and ultrasonography reports of patients with breast carcinoma were reviewed. Data were collected for 406 cases. Concordance was defined as a size difference within ±2 mm. RESULTS: The difference between radiologic and pathologic tumor size was within ±2 mm in 40.4% cases. The mean radiologic size was 1.73 ± 1.06 cm. The mean pathologic size was 1.84 ± 1.24 cm. A paired t-test showed a significant mean difference between radiologic and pathologic measurements (0.12 ± 1.03 cm, p = 0.03). Despite the size difference, stage classification was the same in 59.9% of cases. Radiologic size overestimated stage in 14.5% of cases and underestimated stage in 25.6% of cases. The concordance rate was significantly higher for tumors ≤2 cm (pT1) (51.1%) as compared to those greater than 2 cm (≥pT2) (19.7%) (p < 0.0001). Significantly more lumpectomy specimens (47.5%) had concordance when compared to mastectomy specimens (29.8%) (p < 0.0001). Invasive ductal carcinoma had better concordance compared to other tumors (p = 0.02). CONCLUSION: Mean pathologic tumor size was significantly different from mean radiologic tumor size. Concordance was in just over 40% of cases and the stage classification was the same in about 60% of cases only. Therefore, surgical decision of lumpectomy versus mastectomy based on radiologic tumor size may not always be accurate.

Processing the entire capsule in thyroid follicular lesions improves diagnostic accuracy.

BACKGROUND: There is contradictory evidence in literature with respect to diagnosis and management of follicular lesions of the thyroid gland. From surgical pathology stand point, pathologists require submission and processing of entire capsule for microscopic evaluation. This can be extremely challenging especially in larger lesions. METHOD: We studied the impact of submitting entire capsule on final pathologic diagnosis in cases on which only representative sections were submitted initially and entire capsule was submitted subsequently. RESULTS: A total of 80 specimens were identified. Mean size of the nodule in these cases was 4.4 ±â€¯1.9 cm. Mean initial tissue sections submitted were 11.6 ±â€¯3.6. Entire capsule was submitted subsequently in an additional 12.6 ±â€¯13.3 sections. Submission of entire capsule contributed to final diagnosis in 3 (3.8%) cases whereby foci of capsular microinvasion were identified. There was no significant difference in the requirement of subsequent sections in specimens grossed by residents compared to those grossed by pathologist assistants (10.4 ±â€¯10.8 vs. 14.4 ±â€¯14.9, p = 0.18). The processing cost of additional sections of capsule was $ 4143 in these cases. CONCLUSION: Processing of entire capsule in thyroid follicular lesions has a definitive yield that comes at a high cost. Thin slicing and looking for areas of gross abnormality such as mushrooming may be more practical especially in larger lesions.

Tumor Size in Breast Carcinoma: Gross Measurement Is Important!

INTRODUCTION: The staging of breast carcinoma is mainly dependent on tumor size and lymph node status. Small increments in tumor size upstage the patient. An accurate determination of the tumor size is therefore critically important. Although the final staging is based on microscopic size, pathologists rely on gross measurements in a considerable number of cases. METHODS: We investigated the concordance between gross and microscopic measurements of breast carcinoma as well as factors affecting this concordance. This study is a retrospective review of surgical pathology reports of invasive breast carcinomas. Data were collected for 411 cases. Concordance was defined as a size difference within ±2 mm. RESULTS: Gross and microscopic sizes were identical in 33.1% of cases. Gross and microscopic size difference was within ±2 mm in 56% of cases. Despite the size difference, stage classification ended up being the same in 68.6% of cases. Tumor stage was over estimated by gross measurement in 17.0% of cases and underestimated in 14.4% of cases. The concordance was significantly higher for those tumors in which final pathologic tumor (pT) size was greater than 2 cm (≥pT2) as compared with those less than or equal to 2 cm (≤pT1; P < .0001). A higher proportion of mastectomy specimens (61.4%) were concordant as compared with lumpectomy specimens (52.1%). CONCLUSION: Gross and microscopic tumor sizes were concordant in 56% of cases. Stage classification based on gross and microscopic tumor size was different in nearly one third (31.4%) of cases. Gross tumor size is critically important in accurate staging at least in cases where tumor size cannot be confirmed microscopically.

Diagnostic challenges and problem cases in salivary gland cytology: A 20-year experience.

BACKGROUND: Fine-needle aspiration (FNA) is routinely performed to evaluate salivary gland lesions, and provides valuable information regarding the cytomorphologic features of the lesions. Occasionally, there are overlaps between benign and malignant conditions due to heterogeneity of the cell types, metaplastic changes, and sampling issues. Herein, the authors present a retrospective study of diagnostic pitfalls in salivary gland cytology and the simulating conditions. METHODS: A 20-year retrospective review (1995-2015) of medical records was performed searching for the cytology reports of patients who underwent FNA of the salivary gland with the words "amendment" or "revision." Medical records of the revised cases were reviewed for the subsequent surgical follow-up. All cases with a diagnostic discrepancy between the primary cytologic diagnosis and the final histology diagnosis were included in the current study. The histologic diagnosis was considered the gold standard. RESULTS: A total of 19 cases were included in the current study. The cases were divided into 7 categories based on their cytologic diagnoses: 1) nondiagnostic (1 case); 2) benign, nonneoplastic lesion (2 cases); 3) benign salivary gland neoplasm (2 cases); 4) salivary gland neoplasm (4 cases); 5) epithelial neoplasm, not otherwise specified (1 case); 6) markedly atypical cells suspicious for a malignant neoplasm (1 case); and 7) malignant neoplasms (8 cases). CONCLUSIONS: The interpretation of salivary gland FNA can be influenced by several factors including prominent metaplasia, focal atypia, cystic changes, variable cellular components within the lesions, scant cellularity, variants of neoplasms, and a prior history of malignancy. Multiple passes representing the entire mass, imaging findings, and familiarity with salivary gland cytomorphology may improve the diagnostic accuracy. Cancer Cytopathol 2018;126:101-11. © 2017 American Cancer Society.

Pulmonary placental transmogrification associated with adenocarcinoma of the lung: a case report with a comprehensive review of the literature.

Pulmonary placental transmogrification (PT) is a rare entity with less than 40 cases reported in the literature. Most reported cases are associated with either bullous emphysema or with pulmonary fibrochondromatous hamartomas. We present only the second case of PT associated with adenocarcinoma of the lung. A 67-year-old female with multiple chronic medical ailments presented with shortness of breath and was found to have a 6-cm mass in the upper lobe of her right lung. A computed tomography (CT) guided core biopsy was performed that showed a well-differentiated adenocarcinoma. Interestingly the normal lung tissue showed placental villous architecture. A unique feature of our case is that the diagnosis was made on a needle core biopsy, unlike all the other cases in the literature. We also provide a comprehensive review of this rare entity.

Pulmonary placental transmogrification associated with adenocarcinoma of the lung: a case report with a comprehensive review of the literature

Pulmonary placental transmogrification (PT) is a rare entity with less than 40 cases reported in the literature. Most reported cases are associated with either bullous emphysema or with pulmonary fibrochondromatous hamartomas. We present only the second case of PT associated with adenocarcinoma of the lung. A 67-year-old female with multiple chronic medical ailments presented with shortness of breath and was found to have a 6-cm mass in the upper lobe of her right lung. A computed tomography (CT) guided core biopsy was performed that showed a well-differentiated adenocarcinoma. Interestingly the normal lung tissue showed placental villous architecture. A unique feature of our case is that the diagnosis was made on a needle core biopsy, unlike all the other cases in the literature. We also provide a comprehensive review of this rare entity.

Developmental and endocrine regulation of kisspeptin expression in mouse Leydig cells.

Kisspeptin, encoded by the Kiss1 gene, binds to a specific G protein-coupled receptor (kisspeptin1 receptor) to regulate the central reproductive axis. Kisspeptin has also been reported to be expressed in peripheral tissues, including the testes. However, factors regulating testicular kisspeptin and its role in reproduction are unknown. Our objective herein was to begin to address kisspeptin function in the testis. In particular, we sought to determine the level of kisspeptin in the testis in comparison with the brain and other tissues, how these levels change from the prepubertal period through sexual maturation, and the factors involved in kisspeptin regulation in the testis. Immunohistochemical analysis of testis sections using a validated kisspeptin antibody localized kisspeptin to the Leydig cells. Kisspeptin was not detected in germ cells or Sertoli cells within the seminiferous tubules at any developmental time period studied, from prepuberty to sexual maturation. A developmental time course of testicular kisspeptin revealed that its mRNA and protein levels increased during development, reaching robust levels at postnatal day 28, correlating with pubertal onset. In vitro studies of primary mouse Leydig cells, as well as in vivo studies, indicated clearly that LH is involved in regulating levels of Leydig cell kisspeptin. Interestingly, gonadectomy resulted in elevated LH but reduced serum kisspeptin levels, suggesting that testicular kisspeptin may be secreted. These data document kisspeptin expression in mouse Leydig cells, its secretion into peripheral serum, and its regulation by changes in reproductive neuroendocrine function.

Insulin regulates the unfolded protein response in human adipose tissue.

Endoplasmic reticulum (ER) stress is increased in obesity and is postulated to be a major contributor to many obesity-related pathologies. Little is known about what causes ER stress in obese people. Here, we show that insulin upregulated the unfolded protein response (UPR), an adaptive reaction to ER stress, in vitro in 3T3-L1 adipocytes and in vivo, in subcutaneous (sc) adipose tissue of nondiabetic subjects, where it increased the UPR dose dependently over the entire physiologic insulin range (from ∼ 35 to ∼ 1,450 pmol/L). The insulin-induced UPR was not due to increased glucose uptake/metabolism and oxidative stress. It was associated, however, with increased protein synthesis, with accumulation of ubiquitination associated proteins, and with multiple posttranslational protein modifications (acetylations, methylations, nitrosylations, succinylation, and ubiquitinations), some of which are potential causes for ER stress. These results reveal a new physiologic role of insulin and provide a putative mechanism for the development of ER stress in obesity. They may also have clinical and therapeutic implications, e.g., in diabetic patients treated with high doses of insulin.

Comparison of in vivo effects of insulin on SREBP-1c activation and INSIG-1/2 in rat liver and human and rat adipose tissue.

OBJECTIVE: The stimulatory effects of insulin on de novo lipogenesis (DNL) in the liver, where it is an important contributor to non-alcoholic fatty liver disease (NAFLD), hepatic and systemic insulin resistance, is strong and well established. In contrast, insulin plays only a minor role in DNL in adipose tissue. The reason why insulin stimulates DNL more in liver than in fat is not known but may be due to differential regulation of the transcription and post-translational activation of sterol regulatory element binding proteins (SREBPs). To test this hypothesis, we have examined effects of insulin on activation of SREBP-1c in liver of rats and in adipose tissue of rats and human subjects. DESIGN AND METHODS: Liver and epidydimal fat were obtained from alert rats and subcutaneous adipose tissue from human subjects in response to 4 h euglycemic-hyperinsulinemic clamps. RESULTS: Here we show that acutely raising plasma insulin levels in rats and humans increased SREBP-1 mRNA comparably 3-4 fold in rat liver and rat and human adipose tissue, but increased post-translational activation of SREBP-1c only in rat liver, while decreasing it in adipose tissue. These differential effects of insulin on SREBP-1c activation in liver and adipose tissue were associated with robust changes in the opposite direction of INSIG-1 and to a lesser extent of INSIG-2 mRNA and proteins. CONCLUSIONS: We conclude that these findings support the hypothesis that insulin stimulated activation of SREBP-1c in the liver, at least in part, by suppressing INSIG-1 and -2, whereas in adipose tissue, an increase in INSIG-1 and -2 prevented SREBP-1c activation.

Why does obesity increase the risk for cardiovascular disease?

Insulin resistance and inflammation are recognized as important links between obesity and cardiovascular disease (CVD). Plasma free fatty acids (FFA), either released from the abnormally enlarged adipose tissue or as part of the excessive nutrient intake, produce insulin resistance and inflammation. Both insulin resistance and inflammation are tightly linked to several independent CVD risk factors such as type 2 diabetes (T2DM), hypertension, dyslipidemia and disorders of blood coagulation. Several hypotheses have been proposed to explain how increased plasma FFA levels can cause insulin resistance including a) the lipid metabolite hypothesis, b) the inflammation hypothesis, c) the hyperinsulinemia hypothesis and d) the endoplasmic reticulum (ER) stress hypothesis. The latter does not require presence of elevated plasma FFA levels and thus provides a mechanism to explain the development of insulin resistance and inflammation in all obese individuals, i.e., those with and without elevated plasma FFA levels. Hyperinsulinemia per se has been suspected to cause CVD based on epidemiologic studies which have associated chronic hyperinsulinemia with CVD without, however, establishing a cause and effect relationship. There are, however, newer results which support the hypothesis that chronic hyperinsulinemia per se can promote the development of CVD. For instance, hyperinsulinemia can activate triglyceride formation, several matrix metalloproteinases (MMP), and the tissue factor pathway of blood coagulation, all of which are known to be associated with CVD, even in the presence of "metabolic insulin resistance".