Laila Khazai

Evaluation of ThyroSeq v2 performance in thyroid nodules with indeterminate cytology

ThyroSeq v2 claims high positive (PPV) and negative (NPV) predictive values in a wide range of pretest risks of malignancy in indeterminate thyroid nodules (ITNs) (categories B-III and B-IV of the Bethesda system). We evaluated ThyroSeq v2 performance in a cohort of patients with ITNs seen at our Academic Cancer Center from September 2014 to April 2016, in light of the new diagnostic criteria for non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). Our study included 182 patients (76% female) with 190 ITNs consecutively tested with ThyroSeq v2. Patient treatment followed our institutional thyroid nodule clinical pathway. Histologies of nodules with follicular variant papillary thyroid carcinoma or NIFTP diagnoses were reviewed, with reviewers blinded to molecular results. ThyroSeq v2 performance was calculated in nodules with histological confirmation. We identified a mutation in 24% (n = 45) of the nodules. Mutations in RAS were the most prevalent (n = 21), but the positive predictive value of this mutation was much lower (31%) than that in prior reports. In 102 resected ITNs, ThyroSeq v2 performance was as follows: sensitivity 70% (46-88), specificity 77% (66-85), PPV 42% (25-61) and NPV 91% (82-97). The performance in B-IV nodules was significantly better than that in B-III nodules (area under the curve 0.84 vs 0.57, respectively; P = 0.03), where it was uninformative. Further studies evaluating ThyroSeq v2 performance are needed, particularly in B-III.

Institutional prevalence of malignancy of indeterminate thyroid cytology is necessary but insufficient to accurately interpret molecular marker tests

OBJECTIVE Several molecular marker tests are available to refine the diagnosis of thyroid nodules. Knowing the true prevalence of malignancy (PoM) within each cytological category is considered necessary to select the most appropriate test and to interpret results accurately. We describe our institutional PoM among cytological categories and report our experience with molecular markers. DESIGN Single-center retrospective study. METHODS We calculated the institutional PoM for each category of the Bethesda system (Bethesda) on all thyroid nodules with cytological evaluation from October 2008 to May 2014. We estimated the predictive values for Afirma, miRInform, and ThyroSeq v2, based on published sensitivity and specificity. Finally, we assessed our own experience with miRInform. RESULTS The PoMs for Bethesda III and IV categories were 21 and 28%, respectively. ThyroSeq v2 achieves the highest theoretical negative and positive predictive values (NPV and PPV) in Bethesda III (98 and 75%) and Bethesda IV categories (96 and 83%). At our institution, miRInform detected a mutation in 16% of 109 indeterminate nodules tested, all in Bethesda IV specimens. Histology was available in 56 (51%) nodules. The observed sensitivity and specificity in Bethesda IV specimens were 63 and 86%, yielding an NPV and a PPV of 75 and 77%, respectively. CONCLUSIONS For our current Bethesda III and IV PoM, the actual performance of miRInform was worse than expected. Theoretically ThyroSeq v2 should have the best performance, but it could be affected in the same way as miRInform, given the similarities between the tests. Assessing the institutional performance of each test is necessary along with PoM individualization.

Use of Immunohistochemical Stains in Epithelial Lesions of the Breast.

BACKGROUND During the last few decades, immunohistochemistry (IHC) has become an integral part of pathology. Although hematoxylin and eosin (H & E) stain remains the fundamental basis for diagnostic pathology of the breast, IHC stains provide useful and sometimes vital information. Moreover, considering the role of hormonal therapy in hormone receptor-positive breast tumors, as well as the availability of targeted chemotherapeutic agents for HER2-positive cases, IHC studies represent a major part of workups. METHODS A literature search was performed to explore the uses of IHC stains related to the diagnoses of breast lesions and prognostic/predictive information. RESULTS Selective use of IHC stains in conjunction with H & E examination helps resolve most diagnostic issues encountered by surgical pathologists during their day-to-day practice. Pathologists should be familiar with the use of each immunostain and its limitations to avoid interpretative errors. CONCLUSIONS IHC stains help guide the differential diagnosis of challenging epithelial lesions of the breast. They should be selectively and judiciously used and their findings must be interpreted with the differential diagnoses in mind and with an understanding of possible pitfalls.

Imaging Findings and Management of Primary Breast Cancer in Accessory Axillary Breast Tissue

Primary breast cancer presenting in ectopic axillary breast tissue comprises < 1% of all breast cancers each year. These rare presentations are easily mistaken for axillary nodal metastasis, which might be detrimental to the patient. We present a series of 3 patients all treated at a single tertiary cancer center and propose a management algorithm for this unusual presentation. Comprehensive imaging, including magnetic resonance imaging, to rule out occult in-breast disease, is key to the correct diagnosis. Mastectomy is not required in this special population, however, because of the large volume of accessory tissue removed intraoperative drain placement is recommended. Sentinel lymph node biopsy can be successfully performed using a standard dual technique of radioactive tracer and dye. Whole breast radiation is not requisite and systemic therapy should be based on pathologic tumor, node, metastases staging.

Hypermetabolism on (18)F-Fluorodeoxyglucose Positron Emission Tomography Scan Does Not Influence the Interpretation of Thyroid Cytopathology, and Nodules with a SUVmax <2.5 Are Not at Increased Risk for Malignancy.

BACKGROUND Hypermetabolism of thyroid nodules on (18)F-fluorodeoxyglucose positron emission tomography (PET) is associated with a higher prevalence of malignancy. However, the definition of hypermetabolism and its impact on cytological interpretation are unclear. METHODS Medical records of all patients with thyroid nodules who had undergone cytological evaluation at the Moffitt Cancer Center between October 2008 and May 2014 were retrospectively reviewed. Those with a PET scan performed within one year of the cytology composed the study group, and the rest were used as controls. The distribution of the cytological categories, percentage of resection, and prevalence of malignancy among each Bethesda category was compared between both groups. RESULTS Fifteen percent (436) of all thyroid nodules with cytological evaluation were in the study group. Maximum standardized uptake values (SUVmax) were directly associated with the probability of having a malignant or a follicular neoplasm cytological diagnosis; and inversely associated with the probability of having a benign cytological diagnosis. However, the prevalence of cancer within each Bethesda category was not associated with SUVmax values. It was found that the prevalence of malignant cytology increased to >5% with SUVmax values ≥2.5. SUVmax values were significantly higher in malignant than in benign nodules on histology (mean values 10.8 vs. 5) but with significant overlap between both groups for either the whole cohort or nodules with indeterminate cytology only limiting its use for differential diagnosis. CONCLUSIONS The prevalence of malignancy in thyroid nodules with a SUVmax <2.5 is similar to the general population, and management should not be modified in those patients. The increased prevalence of malignancy among hypermetabolic thyroid nodules (SUVmax ≥2.5) is well characterized by cytology and does not impact the interpretation of cytological categories. Therefore, SUVmax value does not add relevant information once cytology is available.

Impact of oncogene panel results on surgical management of cytologically indeterminate thyroid nodules

The impact of oncogene panel results on the surgical management of indeterminate thyroid nodules (ITNs) is currently unknown.

Association of Tumor Size With Histologic and Clinical Outcomes Among Patients With Cytologically Indeterminate Thyroid Nodules

Importance Tens of thousands of unnecessary operations are performed each year for diagnostic purposes among patients with cytologically indeterminate thyroid nodules. Whereas a diagnostic lobectomy is recommended for most patients with solitary indeterminate thyroid nodules, a total thyroidectomy is preferred for nodules larger than 4 cm. Objective To determine whether histologic or clinical outcomes of indeterminate thyroid nodules 4 cm or larger are worse than those for nodules smaller than 4 cm, thus justifying a more aggressive initial surgical approach. Design, Setting, and Participants In this retrospective cohort study, 652 indeterminate thyroid nodules (546 nodules <4 cm and 106 nodules ≥4 cm) with surgical follow-up were consecutively evaluated at an academic cancer center from October 1, 2008, through April 30, 2016. Exposure Tumor size. Main Outcomes and Measures Differences in cancer rates, rates of invasive features, cancer aggressiveness, and response to therapy between indeterminate thyroid nodules smaller than 4 cm and 4 cm or larger. Results A total of 652 indeterminate thyroid nodules (546 nodules <4 cm and 106 nodules ≥4 cm) from 589 patients (mean [SD] age, 53.1 [13.8] years; 453 [76.9%] female) were studied. No differences were found in the baseline characteristics of patients or nodules between the 2 size groups. Tumor size was not associated with the cancer rate as a categorical (140 of 546 [25.6%] for nodules <4 cm and 33 of 106 [31.1%] for nodules ≥4 cm; effect size, 0.05; 95% CI, 0.002-0.12) or continuous (odds ratio [OR], 1.03; 95% CI, 0.92-1.15) variable. No association was found between nodule size and prevalence of extrathyroidal extension, positive margins, lymphovascular invasion, lymph node metastasis, or distant metastasis. Most malignant tumors were low risk in both size groups (70% in the nodules <4 cm and 72% in the nodules ≥4 cm), and tumor size was not associated with tumor aggressiveness as a categorical (effect size, 0.10; 95% CI, 0.03-0.31) or continuous variable (OR for intermediate-risk cancer, 0.91; 95% CI, 0.72-1.14; OR for high-risk cancer, 1.43; 95% CI, 0.96-2.15). At the last follow-up visit, 88 of 105 patients (83.8%) with malignant tumors in the smaller than 4 cm group and 21 of 25 (84.0%) in the 4 cm or greater group had no evidence of disease, and tumor size was not associated with response to therapy (effect size, 0.13; 95% CI, 0.07-0.33). Conclusions and Relevance Most indeterminate thyroid nodules are benign or low-risk malignant tumors regardless of tumor size. In the absence of other indications for total thyroidectomy, this study suggests that a thyroid lobectomy is sufficient initial treatment for most solitary cytologically indeterminate thyroid nodules independent of the tumor size.

Papillary endothelial hyperplasia arising in the irradiated breast: A diagnostic dilemma.

Papillary endothelial hyperplasia (PEH) is a benign proliferative lesion that may occur in any site of the body, but most commonly affects the skin and subcutaneous tissues. In the breast, PEH has been documented but is rare. PEH is notorious for being misdiagnosed as angiosarcoma due to its complex growth pattern, papillary processes and interlacing vascular channels. The occurrence of PEH years after breast irradiation constitutes a pathological and clinical diagnostic challenge because angiosarcoma is far more common in this setting. The most important features that differentiate papillary endothelial hyperplasia from angiosarcoma are its presentation as a round nodule without infiltrative borders, its localization inside a vessel or in association with thrombus, and the lack of significant cytologic atypia or areas of solid growth, even in the presence of a complex architecture. Clinical history and site of involvement (cutaneous versus parenchymal) are usually of help to establish a correct diagnosis. Herein, we describe two cases of PEH presenting in patients with history of breast carcinoma and breast radiation therapy. The clinical and morphological features as well as the differential diagnoses are discussed. To our knowledge, no other cases of PEH of the breast occurring in the post-radiation setting have been described in the literature.

Metastatic Salivary Duct Carcinoma to the Breast.

abscesses. The process of osseous metaplasia also occurs in the setting of trauma and soft-tissue tumors. The mechanism of formation is suggested to begin with the metaplasia of fibroblasts to osteoblasts. While the mechanism of metaplasia in the setting of neoplasm has been described as epithelial–stromal metaplasia or mesenchymal–stromal origin, the mechanism is not well understood in non-neoplastic settings. Keyoung et al. hypothesized that benign cases of heterotopic ossification might be secondary to chronic inflammatory or degenerative changes in the breast as seen in chronic mastitis. There is a distinction, however, between “ossifying-type” calcifications and true osseous metaplasia. Bone formation requires the presence of osteocytes in a matrix lined by osteoblasts, and it illuminates on polarizing microscopy, as in the above cases. In contrast, ossifying-type calcifications are surrounded by a bonelike matrix but do not contain osteocytes or osteoblasts. These types of calcifications are usually seen in association with columnar cell proliferations. To our knowledge, only three cases have been previously reported of benign osseous metaplasia in the breast without any underlying medical condition or neoplasm. The presence of associated fat necrosis in the first case presented here raises the possibility of remote trauma, however none was reported. In the second case, the patient’s medications included Vitamin D, however, there was no documented hypercalcemia. In both cases, the calcifications had a “dendritic appearance,” and resembled each other as well as two of the case reports in the literature. Thus, isolated grouped breast calcifications with a “dendritic” appearance might prompt the possibility of osseous metaplasia as a differential consideration.

Invasive Breast Carcinoma Tumor Size on Core Needle Biopsy: Analysis of Practice Patterns and Effect on Final Pathologic Tumor Stage

Introduction In the absence of nodal metastasis, pathologic tumor (pT) size remains one of the most important factors in adjuvant treatment decisions and patient prognosis in breast cancer. The aim of this study was to evaluate the effect of core needle biopsy (CNB) tumor size on final pT stage. Materials and Methods Our information system was searched to identify all patients who underwent excisional procedures for invasive breast carcinoma from January 1, 2014 to December 31, 2015. The tumor size on CNB and final excision, the number of cases in which the CNB size was larger, and the percentage of cases in which using the CNB tumor size changed the final pT stage were recorded. Results From 1380 primary breast excisions/mastectomies, a total of 870 cases were included. In 82 (9.4%) the CNB tumor size was larger (63 of 82 cases) or no residual tumor was identified on excision (19 of 82 cases). From these 82 cases, 40 (48.7%) were properly staged on the basis of CNB tumor size, 16 (19.5%) were not staged, and 26 (31.7%) were staged using the final excision tumor size. Change in stage occurred in 7 of these 26 patients. Conclusion Our study revealed that in most cases, the largest tumor size is found in the excision/mastectomy specimen. However, in 9.4% (82 of 870), the CNB contains the most accurate tumor size for pT staging. On the basis of our results, including the largest linear tumor extent on the CNB report is recommended. Micro‐Abstract In this study we evaluated the effect of core needle biopsy (CNB) tumor size on final pathologic tumor (pT) stage. The laboratory information system was retrospectively reviewed for breast excisional specimens. In 82 of 870 cases (9.4%) the CNB contains the most accurate tumor size for pT staging. Including the largest linear tumor extent on the CNB report is recommended.