Joseph Sailors

Regulation of the CTL response by macrophage migration inhibitory factor.

Macrophage migration inhibitory factor (MIF) has been shown to be a pivotal cytokine that mediates host inflammatory and immune responses. Recently, immunoneutralization of MIF has been found to inhibit tumor growth in mice; however, the contributing mechanisms underlying this effect have not been well defined. We investigated whether MIF plays a regulatory role in the expression of CTL activity. In a mouse model of the CTL response using the OVA-transfected tumor cell line EL4 (EG.7), we found that cultures of splenocytes obtained from EG.7-primed mice secrete high levels of MIF following Ag stimulation in vitro. Notably, parallel splenocyte cultures treated with neutralizing anti-MIF mAb showed a significant increase in the CTL response directed against EG.7 cells compared with control mAb-treated cultures. This effect was accompanied by elevated expression of IFN-γ. Histological examination of the EG.7 tumors from anti-MIF-treated animals showed a prominent increase in both CD4+ and CD8+ T cells as well as apoptotic tumor cells, consistent with the observed augmentation of CTL activity in vivo by anti-MIF. This increased CTL activity was associated with enhanced expression of the common γc-chain of the IL-2R that mediates CD8+ T cell survival. Finally, CD8+ T lymphocytes obtained from the spleens of anti-MIF-treated EG.7 tumor-bearing mice, when transferred into recipient tumor-bearing mice, showed increased accumulation in the tumor tissue. These data provide the first evidence of an important role for MIF in the regulation and trafficking of anti-tumor T lymphocytes in vivo.

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.

Histologic Transformation from Adenocarcinoma to Squamous Cell Carcinoma as a Mechanism of Resistance to EGFR Inhibition

e86 Journal of Thoracic Oncology ® • Volume 10, Number 9, September 2015 CASE REPORT A 66-year-old white female without a history of smoking presented with new onset chest discomfort and dyspnea. Chest imaging demonstrated a large left lower lobe mass, pleural deposits, and a left pleural effusion. Percutaneous biopsy (Fig. 1A) and pleural fluid analyses demonstrated adenocarcinoma consistent with a lung primary (Fig. 2A, C, E, G, I). The patient received four cycles of carboplatin–pemetrexed with partial response. After two cycles of maintenance pemetrexed monotherapy, disease progression occurred. Molecular analysis of the original biopsy demonstrated an activating exon 19 EGFR mutation. Erlotinib was initiated with excellent clinical and radiographic response (Fig. 1B and C). Eight months later, the patient experienced disease progression. Repeat biopsy near the initial biopsy site (Fig. 1D) demonstrated squamous cell carcinoma (Fig. 2B, D, F, H, J) with persistent exon 19 EGFR mutation (Fig. 3) and no evidence of T790M mutation. The patient’s functional status declined, and she developed paraneoplastic leukocytosis (WBC 73 × 10/mm) and hypercalcemia (calcium 12.5 mg/dL). She died shortly thereafter.

Multiple vaginal wall cysts: diagnosis and surgical management.

BACKGROUND: Simple cysts of the female genital tract may become symptomatic and require surgical removal. CASE: A 20-year-old woman had complaints of a vaginal bulge, pelvic pressure, dyspareunia, and stress urinary incontinence. Two cystic masses were seen in the vagina. A magnetic resonance imaging scan revealed 2 additional larger cysts. Urodynamic evaluation was significant for stress incontinence at 200 mL and a Valsalva leak-point pressure of 51 cm H20. The 2 smaller cysts were removed intact through a superficial incision. The larger cysts were intentionally ruptured and dissected out. Histologic examination revealed a low cuboidal or a ciliated columnar epithelium that stained positive with mucicarmine, consistent with müllerian origin. One year after surgical excision, the patient remained symptom free with no urinary incontinence and no recurrence of the cysts. CONCLUSION: Magnetic resonance imaging was useful in delineating the course and anatomic arrangement of the vaginal cysts, but more importantly, identified another cyst that was not readily apparent at physical examination.

Systemic Amyloidosis Presenting as Chronic Diarrhea in a Patient With Ankylosing Spondylitis

Secondary (AA) amyloidosis is a disease that is caused by systemic deposition of amyloid fibrils. Circulating serum amyloid A protein is an acute phase reactant and levels are therefore high during inflammatory states. Chronic elevation of serum amyloid A levels results in accumulation and deposition in various organs, leading to organ dysfunction. Unless the inciting inflammatory state can be controlled, the subsequent development of amyloidosis diminishes patient survival. We report a case of systemic amyloidosis that presented primarily as chronic diarrhea in a patient with ankylosing spondylitis. Unfortunately for the patient, the diagnosis of amyloidosis was delayed for years despite encounters with multiple physicians. Early medical intervention to control chronic inflammation is imperative and could prevent morbidity and mortality related to the development of secondary amyloidosis. Consideration of amyloidosis as a diagnosis in patients who have chronic uncontrolled inflammatory conditions is also important in preventing poor outcomes related to this disease.

First-Line Use of Vemurafenib to Enable Thyroidectomy and Radioactive Iodine Ablation for BRAF-Positive Metastatic Papillary Thyroid Carcinoma A Case Report

Background. Patients with metastatic or radioactive iodine refractory papillary thyroid carcinoma (PTC) have poor prognosis due to ineffective therapy for this condition beyond surgery and radioactive iodine (RAI or 131I). BRAF mutation occurs in more than 44% of PCT. Tyrosine kinase inhibitors, the most commonly used agents for these patients, have weak BRAF inhibition activity. BRAF inhibitors have demonstrated promising efficacy in relapsed metastatic PCT after standard treatment, though they are not currently approved for this indication. Case Presentation. We present the case of a 48-year-old Hispanic male who initially presented with columnar-cell variant subtype of PTC and positive BRAFV600E mutation. The patient had widespread bulky metastases to lungs, chest wall, brain, and bone. Discussion. Initial use of vemurafenib demonstrated a 42% cytoreduction of targeted pulmonary metastases and facilitated thyroidectomy and RAI treatment. The patient achieved a durable response over 21 months in the setting of widely metastatic disease. Conclusion. Vemurafenib may be effectively used for cytoreduction in patients with bulky metastatic PTC to bridge them to thyroidectomy and RAI treatment.

Histologic transformation of EGFR mutant lung adenocarcinoma without exposure to EGFR inhibition

Resistance to EGFR kinase inhibitors appears to be invariable in the treatment of non-small cell lung cancer. Several mechanisms have been described. Here, we report the first case of histologic transformation of EGFR mutant lung adenocarcinoma without prior exposure to EGFR inhibition.

Unruptured second‐trimester ovarian pregnancy

Ovarian ectopic pregnancies are rare, with the majority diagnosed in the first trimester and often treated due to symptoms related to ovarian rupture. We report our experience with the diagnosis, management, and histologic evaluation of an unruptured second‐trimester ovarian ectopic pregnancy. A 37‐year‐old woman presented with vague abdominal discomfort and irregular menses. Ultrasound detected a 16‐week 4‐day gestation with cardiac motion in the right adnexa and no evidence of an intrauterine pregnancy. Laparotomy with right salpingo‐oophorectomy was performed, with removal of an unruptured pregnancy from the ovary. Although intraoperative examination and postoperative histopathologic evaluation demonstrated the classic Speigelberg criteria, it did not assist in the preoperative diagnosis, nor impact the treatment of the ovarian ectopic pregnancy in this case.

Utility and proposed algorithm of CSF flow cytometry in hematologic malignancies

In patients with hematologic malignancies, multiparameter flow cytometry (FCM) offers greater sensitivity than cytology in detecting malignant cells in the initial cerebrospinal fluid (CSF) specimen. However, the role of FCM in assessment of subsequent specimens is unclear. We developed an algorithm to reduce the number of low-yield FCM tests without significant impact on clinically meaningful results. Patients with hematologic malignancies were studied in a derivation cohort, and the following algorithm was developed: (1) cytology and FCM on all initial samples, (2) cytology on all subsequent samples, and (3) FCM on subsequent samples only if previous FCM was positive. A separate population served as the validation cohort. The derivation cohort included 197 patients representing 1157 cytology and 543 FCM samples. Common malignancies were B-Cell ALL (25.3%), diffuse large B cell lymphoma (29.4%), and Burkitt lymphoma (7.7%). In the derivation cohort, the algorithm yielded a sensitivity of 90.0% (95% CI, 81.2–95.6%) and a specificity of 100% (95% CI, 98.9–100.0%). The validation cohort included 132 patients with 563 cytology and 602 FCM samples. In the validation cohort, the testing algorithm yielded a sensitivity of 87.5% (95% CI, 75.9–94.8%) and a specificity of 100% (95% CI, 99.1–100.0%). Of the 15 samples that were missed by the algorithm, FCM findings did not impact patients’ management because of known CNS disease (seven patients) or they were responding to treatment (eight patients). CSF testing in hematologic malignancies using the proposed algorithm presents an evidence-based approach to reduce the number of unnecessary FCM tests of CSF without compromising patient care.

Upper lip metastasis of sarcomatoid carcinoma of the lung – an unusual site of disease: a case report

BackgroundLip metastases are rare clinical events that are frequently mistaken for other diagnoses. For sarcomatoid lung carcinoma, a rare histologic variant of non-small cell lung cancer, the incidence and pattern of cutaneous spread is poorly understood.Case presentationWe present a case of a 79-year-old African American man with a rapidly progressive upper lip cutaneous lesion that provided the first evidence of distant metastatic spread of sarcomatoid lung carcinoma.ConclusionsThis is the first reported case of lip metastasis in sarcomatoid lung carcinoma. It highlights the importance of maintaining a high level of suspicion for metastatic disease in the presence of new cutaneous findings as they may be the first evidence of advanced disease.