Impact of Simultaneous Circulating Tumor DNA and Tissue Genotyping in the Workup of Stage IV Lung Adenocarcinoma on Quality of Care in an Academic Community Medical Center.

PURPOSE: In patients with metastatic lung adenocarcinoma, evidence-based first-line treatment decisions require analysis of tumors for genomic alterations (GAs). Optimizing the genotyping paradigm may improve the delivery of precision oncology care. Actionable GAs can be identified by analyzing tumor tissue or circulating tumor DNA using liquid biopsy. Consensus guidelines for when to use liquid biopsy have not been established. We evaluated the routine use of liquid biopsy performed simultaneously with tissue testing in patients with newly diagnosed, stage IV lung adenocarcinoma. METHODS: We performed a retrospective study comparing patients who underwent tissue genotyping alone (standard biopsy group) with patients who had simultaneous liquid and tissue genotyping (combined biopsy group). We examined the time to reach a final diagnosis, the need for repeat biopsies, and diagnostic accuracy. RESULTS: Forty two patients in the combined biopsy group and 78 in the standard biopsy group met the inclusion criteria. The standard group had a mean time to diagnosis of 33.5 days, compared with 20.6 days in the combined group (P < .001 by two-tailed t-test). In the combined group, 14 patients did not have sufficient tissue for molecular analysis (30%); however, in 11 (79%) of these patients, liquid biopsy identified a GA that eliminated the need for a second tissue biopsy. In patients who completed both tests, each test found actionable GAs missed by the other. CONCLUSION: Performing liquid biopsy simultaneously with tissue genotyping is feasible in an academic community medical center. Potential advantages of simultaneous liquid and tissue biopsies include shorter time to obtain a definitive molecular diagnosis, reduced need for a repeat biopsy, and improved detection of actionable mutations, although a sequential strategy that saves costs by beginning with a liquid biopsy may be ideal.

Paraganglioma of the Spermatic Cord With Spinal Metastasis: A Case Report.

A 40-year-old male with presented to the clinic with the chief complaint of right inguinal pain radiating to his right testicle and right thigh with no history of trauma, fever, chills, dysuria, hematuria, or unprotected sexual activity. Physical exam revealed right testicular tenderness with no palpable abnormality of the bilateral testes or spermatic cords. Scrotal ultrasound was performed and was unremarkable for testicular or other intrascrotal pathology. Concurrently, chronic low back pain had prompted a lumbar CT to be performed, which was indeterminate, but subsequent lumbar MRI performed three months later revealed abnormal signals in the vertebral bodies of T12, L3, and L5, concerning for occult metastatic disease or multiple myeloma. PET-CT was performed revealing hypermetabolic lesions throughout the axial skeleton and, most notably, hypermetabolic lesions in the left inguinal and left upper scrotum. At this time, about 4 months after the original visit, physical exam revealed a palpable mobile mass in the left upper scrotum that was distinct from the left testicle, and another mass palpable near the left inguinal ring.

Correlation of positron emission tomography with fine needle aspiration biopsies in head and neck malignancy.

OBJECTIVE: To investigate whether a correlation between fine needle aspiration cytology and positron emission tomography (PET) exists in the preoperative screening, staging and diagnosis of head and neck cancer. STUDY DESIGN: We retrospectively correlated fine needle aspiration biopsy (FNAB) and PET scan in patients with head and neck lesions. RESULTS: There were 92 FNABs with corresponding PET scan in 83 patients. Mean standard uptake value (SUV) for benign lymph nodes was 5.05 (SD, 5.79), and 13.56 (SD, 6.38) and 16.99 (SD, 19.04) for squamous carcinoma and other malignancies, respectively. Ideal SUV cutoff value was determined to be 6.0. Of 66 malignant FNABs, 52 had an SUV > or = 6, 8 had an SUV < 6, and 6 were interpreted as "hypermetabolic." Of 26 benign FNAB (SUV was available for 17), 8 were interpreted as "hypermetabolic" and 1 as "not hypermetabolic." Of those with SUVs reported, 15 were < 6 while 2 were > or = 6. CONCLUSION: Lesions with SUV 6 are more likely to harbor malignancy, while lesions with repeatedly negative FNAB in the context of SUV > 6 should be considered for open biopsy. Further, lesions with SUV < 6 may harbor malignancy and therefore fine needle aspiration biopsy is also recommended.

Guanylyl cyclase C is a specific marker for differentiating primary and metastatic ovarian mucinous neoplasms.

AIMS: The aim was to assess the value of GCC in distinguishing primary ovarian mucinous neoplasms from metastatic mucinous adenocarcinomas with ovarian involvement. Guanylyl cyclase C (GCC) is a brush border membrane receptor for the endogenous peptides guanylin and uroguanylin, and the homologous diarrhoeagenic bacterial heat-stable enterotoxins that is selectively expressed by epithelial cells from the duodenum to the rectum, but not by normal epithelia of the stomach or oesophagus, or normal extramucosal cells in humans. METHODS AND RESULTS: Fifty ovarian tumours: 27 primary ovarian mucinous neoplasms (seven cystadenomas, 10 borderline tumours and 10 cystadenocarcinomas) and 23 metastatic mucinous adenocarcinomas with ovarian involvement [13 colorectal adenocarcinomas, four gastric adenocarcinomas, six appendiceal mucinous tumours (four adenocarcinomas, one with neuroendocrine features, and two appendiceal mucinous cystadenomas)] were studied. For primary ovarian mucinous neoplasms, 25 of 27 were negative for GCC. Twelve of 13 cases of colorectal adenocarcinoma (except for one neuroendocrine adenocarcinoma) were positive for GCC. Three of four appendiceal mucinous adenocarcinomas were positive for GCC in both the primary and metastatic tumours (except for one neuroendocrine adenocarcinoma). Two of two appendiceal mucinous cystadenomas were positive for GCC. Of four cases of gastric adenocarcinoma with ovarian involvement, only one (primary tumour) exhibited focal GCC staining. CONCLUSIONS: GCC is a useful marker for differentiating between primary and secondary ovarian mucinous neoplasms.

The significance of GATA3 expression in breast cancer: a 10-year follow-up study.

GATA3 is a transcription factor closely associated with estrogen receptor alpha in breast carcinoma, with a potential prognostic utility. This study investigated the immunohistochemical expression of GATA3 in estrogen receptor alpha-positive and estrogen receptor alpha-negative breast carcinomas. One hundred sixty-six cases of invasive breast carcinomas with 10-year follow-up information were analyzed. Positive GATA3 and estrogen receptor alpha cases were defined as greater than 20% of cells staining. Time to cancer recurrence and time to death were analyzed with survival methods. Of 166 patients, 40 were estrogen receptor alpha negative and 121 estrogen receptor alpha positive. Thirty-eight (23%) recurrences and 51 (31%) deaths were observed. In final multivariable analyses, GATA3-positive tumors had about two thirds the recurrence risk of GATA3-negative tumors (hazard ratio = 0.65, P = .395) and comparable mortality risk (hazard ratio = 0.86, P = .730). In prespecified subgroup analyses, the protective effect of GATA3 expression was most pronounced among estrogen receptor alpha-positive patients who received tamoxifen (hazard ratio = 0.57 for recurrence and 0.68 for death). We found no statistically significant differences in recurrence or survival rates between GATA3-positive and GATA3-negative tumors. However, there was a suggestion of a modest-to-strong protective effect of GATA3 expression among estrogen receptor alpha-positive patients receiving hormone therapy.

Cytologic accuracy of samples obtained by endobronchial ultrasound-guided transbronchial needle aspiration at Thomas Jefferson University Hospital.

OBJECTIVE: To evaluate the diagnostic yield and cytologic accuracy of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in cases of clinically suspected epithelial malignancy, sarcoidosis and lymphoma. STUDY DESIGN: Over a 9-month period from inception at Thomas Jefferson University Hospital, a retrospective analysis of the cytologic diagnoses of all EBUS-TBNA procedures performed in 48 patients was undertaken. The patients were divided into 2 groups, those with clinical suspicion of an epithelial malignancy and those with clinical suspicion of sarcoidosis or lymphoma. RESULTS: Of the 48 patients who underwent EBUS-TBNA, 39 had adequate fine needle aspiration biopsy samples (60 of 78) with a diagnostic yield of 77%; the pre-EBUS yield was 58%. For the group with malignant disease the calculated sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were all 100%. For the group with benign disease the calculated sensitivity, specificity, PPV and NPV were also 100%. CONCLUSION: Preliminary results show that cytologic samples obtained via BUS-TBNA are accurate and specific in making a diagnosis of an epithelial malignancy or benign disease.

A prospective feasibility trial to determine the significance of the sentinel node gradient in breast cancer: a predictor of nodal metastasis location.

BACKGROUND: Sentinel lymph node (SN) biopsy is standard for breast cancer staging, but SN dye gradients and their significance have never been characterized. If predictive of SN metastasis location, their use for focused pathology examination might improve intraoperative imprint cytology sensitivity. METHODS: This prospective trial enrolled clinically lymph node-negative patients with invasive breast cancer not undergoing neoadjuvant chemotherapy. Surgeons marked SN gradients at their bluest end. Nodal halves were examined separately by imprint cytology, and the marked SN half was correlated to metastasis location. Demographic, pathologic, and prognostic features were recorded. RESULTS: Mean patient age and tumor size for the 102 patients was 59.6 years and 2.2 cm, respectively. Of 169 SNs, 159 (94.1%) had dye gradients, which varied by tumor quadrant, but not by histology, diagnosis method, grade, or stage. Among 41 marked SNs with metastases, 92.7% were present in the halves marked by the surgeon. Fourteen were confined to 1 nodal half, with 11 on the marked side and 3 on the unmarked side (P = .029). Metastases were smaller when confined to 1 versus both SN halves (0.14 vs 0.75 cm; P = .005), and smaller (0.87 vs 0.13 cm; P < .0001) when missed intraoperatively. CONCLUSIONS: Dye gradients occur in most SNs and predict metastasis location. The smallest metastases are hardest to detect intraoperatively and are usually confined to the marked SN half. This suggests that marking an SN's bluest half warrants further study to explore whether its correlation to metastasis location may be exploited to focus pathologic examination and decrease the reoperative axillary dissection rate.