Alexander M. Truskinovsky

Small-Cell Carcinoma With an Epidermal Growth Factor Receptor Mutation in a Never-Smoker With Gefitinib-Responsive Adenocarcinoma of the Lung

Activating mutations in the epidermal growth factor receptor (EGFR) gene are extremely rare in small-cell lung cancer (SCLC). Here, we present a case of an EGFR-mutant gefitinib-responsive non-small-cell lung cancer (NSCLC) of adenocarcinoma histology occurring in a never-smoker followed by subsequent diagnosis of metastatic SCLC carrying an EGFR mutation. Although gefitinib therapy of the primary NSCLC resulted in disease control for over 3 years, the patient subsequently developed metastatic SCLC to the liver. Epidermal growth factor receptor mutation analysis revealed that the exon 21 L858R activating mutation was present in both the original lung adenocarcinoma and the metastatic SCLC. We hypothesize that SCLC either evolved from the previously diagnosed NSCLC or that both arose from a common precursor. Further comparative molecular analysis of these histologically distinct tumors would be of value to better understand the potential role of EGFR in the pathogenesis of SCLC in never-smokers, and the role of selection for an EGFR-mutant SCLC subclone as an unusual mechanism of acquired resistance to EGFR inhibitors in NSCLC.

Rare case of hemangiopericytoma responds to sunitinib

Hemangiopericytoma (HP) is a rare mesenchymal tumor associated with the capillary wall. We describe a 62-year-old man with a 20-year history of recurrent metastatic HP, in which a favorable clinical benefit was observed with sunitinib, an oral VEGFR, and PDGFR kinase inhibitor. Disease progression was evident during the 3 months before starting sunitinib therapy. Radiologic evaluation indicated that metastatic lesions in the lungs and pelvis remained stable during the 6 months on sunitinib therapy. Histologic analysis of the tumor 3 weeks after active sunitinib therapy did not reveal tumor necrosis, but recanalized thrombi within tumor blood vessels indicated previous tumor insult. Additional studies are warranted to confirm the possible effects of sunitinib in controlling widespread metastatic HP.

Bariatric surgery and endometrial pathology in asymptomatic morbidly obese women: a prospective, pilot study

To determine the prevalence of occult uterine pathology in asymptomatic, morbidly obese women before and after bariatric surgery‐induced weight loss.

Thymic carcinoid responds to neoadjuvant therapy with sunitinib and octreotide: a case report.

Carcinoids are malignant neuroendocrine tumors consisting of a spectrum of neoplasms from low-grade typical carcinoid to high-grade small cell carcinoma. We report a case of atypical thymic carcinoid that responded to neoadjuvant therapy with octreotide and sunitinib, an oral multikinase inhibitor. After 3 weeks of treatment, tumor size significantly decreased to allow for a safe surgical resection with clear margins. We believe that further study of sunitinib and octreotide with the neoadjuvant intent of preparing tumors for resection is warranted as a strategy to improve curative management of neuroendocrine tumors.

Metanephric adenoma of the kidney: an unusual diagnostic challenge

Although metanephric adenoma (MA) is a rare, benign neoplasm of epithelial cells, it is often difficult to distinguish this entity from other malignant neoplasms preoperatively. We report a case of a large renal mass for which preoperative diagnosis was indeterminate, with the differential diagnosis including Wilm’s tumor, MA, and papillary renal cell carcinoma (PRCC). Accurate postoperative differentiation of MA from PRCC is critical because adjuvant therapy is considered after surgical resection of PRCC tumors.

AAV-P125A-endostatin and paclitaxel treatment increases endoreduplication in endothelial cells and inhibits metastasis of breast cancer

Endostatin potentiates the antimitotic effects of paclitaxel (taxol) on endothelial cells (ECs). P125A-endostatin and taxol-treated ECs showed multipolar spindles and nuclear lobulation, leading to mitotic catastrophe and cell death. Induction of nuclear abnormalities was found to be dependent on β-catenin levels as wnt-mediated overexpression of β-catenin reversed the changes in nuclear morphology. These results prompted us to investigate whether antiangiogenic gene therapy and paclitaxel chemotherapy can synergistically inhibit angiogenesis and tumor growth. We first determined the effect of combination treatment in a transgenic mouse model of breast cancer. Intramuscular injection of recombinant adeno-associated virus type-2 virus induced sustained expression of P125A-endostatin. In vivo studies showed that combination therapy inhibited mammary cancer growth, delayed the onset of multifocal mammary adenocarcinomas, decreased tumor angiogenesis and increased survival in treated mice. In a second model, female athymic mice were orthotopically transplanted with a metastatic human breast cancer cell line. Antiangiogenic gene therapy in combination with paclitaxel inhibited tumor angiogenesis and lung/lymph-node metastasis in this model. These studies demonstrate cooperation between endostatin gene therapy and chemotherapy to inhibit tumor initiation, growth and metastasis.

Sorafenib induces partial response in metastatic medullary thyroid carcinoma.

Medullary thyroid carcinoma (MTC) represents approximately 5% of all thyroid carcinomas [1]. In contrast to papillary and follicular thyroid cancers which arise from thyroid hormone-producing cells, MTC originates from calcitonin-producing parafollicular C cells in the thyroid [2]. Mutations in the RET proto-oncogene are present in up to 95% of the less-common familial MTC and are seen in over 50% of sporadic cases [3,4]. Diagnostic testing for calcitonin or RET mutations is of limited use in the early detection of MTC in patients without a family history of MTC. Only 15–30% of patients with advanced or metastatic MTC exhibit a response to conventional treatment with doxorubicin, either as a single agent or in combination with cisplatin plus 5-fluorouracil [5]. Overall, 10-year survival rates are 70% when MTC has invaded cervical lymph nodes and 20% when the disease has metastasized to distant sites. Here, we report a rare case of advanced metastatic MTC that responded to sorafenib, a multikinase inhibitor. A 39-year-old African male presented with a diagnosis of poorly differentiated metastatic neuroendocrine carcinoma at the University of Minnesota Masonic Cancer Center in December 2007. His history with MTC most likely originated in 1990 while he resided in Africa. Past medical history included treatment for schistosomiasis and episodes of hematuria. He was found to have cervical lymph node enlargement, but screening for tuberculosis, HIV-1 and 2, and syphilis was negative. In February 2004, while in the United States, he was found to have a large left supraclavicular soft tissue mass. A restaging CT scan showed multiple metastases within the right lung and mediastinum. In March 2004, cervical lymph node dissection was performed, and a diagnosis of poorly differentiated small cell neuroendocrine carcinoma was made. The patient was treated with cisplatin and etoposide plus radiation to the left upper supraclavicular area. Disease control was maintained until he presented with profuse diarrhea and hypercalcitoninemia in 2007, at which point new metastatic lesions were discovered in the liver and bones, as well as disease progression in the lungs. Therapy with temozolo-mide and bevacizumab was initiated, but after several cycles of this regimen disease progressed. In December 2007, the patient arrived at the University of Minnesota Masonic Cancer Center for treatment. His medication consisted of octreotide and opium for controlling his hypercalcitoninemia/ hypocalcaemia and diarrhea. The patient’s response to typical therapy for small-cell neuroendocrine carcinoma was not satisfactory. The decision was made to start sunitinib based on the noted response of neuroendocrine tumors to sunitinib in a phase 2 randomized trial [6], as well as our own experience. A CT/ PET scan performed on May 22, 2008 showed improvement of metastatic disease in the media stinum and thoracolumbar vertebral column. No significant change was seen in bilateral pulmonary metastases or periaortic lymph nodes. Worsening disease was also noted in the left axilla, liver and sternum. A ct a O nc ol D ow nl oa de d fr om in fo rm ah ea lth ca re .c om b y K ar ol in sk a In st itu te t U ni ve rs ity L ib ra ry o n 06 /1 7/ 14

Large-cell neuroendocrine carcinoma of the cervix

Large cell neuroendocrine carcinoma (LCNEC) of the uterine cervix is a rare and aggressive malignancy with poor prognosis even in its early stage, despite multimodality treatment strategy. Here, we report a case of a woman with clinical polypoid stage IB LCNEC of the cervix, which was detected in her 6-week postpartum checkup. A literature review was also conducted to evaluate current therapeutic approaches and potential new strategies.

Metastatic adamantinoma responds to treatment with receptor tyrosine kinase inhibitor

Adamantinoma is a rare tumor that affects long bones, and it is estimated to account for 0.1 to 0.5% of all primary bone tumors [1]. It is named for its histological similarity to the tumor of the mandible (ameloblastoma). Although its origin remains controversial, recent opinion seems to suggest that adamantinoma is a tumor of epithelial origin, based on ultra structural and immunohistochemical studies [2–4]. Only approximately 200 cases of adamantinoma have been reported since the tumor was first described by Fischer in 1913 [5]. The tumor occurs almost exclusively in long bones, with tumors in the tibia accounting for more than 80% of cases. It is a low-grade neoplasm that presents an indolent course, is locally aggressive and rarely metastasizes. Appropriate surgical treatment may lead to 10-year survival rate of 89.2% [6]. The secondary sites most frequently affected are the lungs [7], lymph nodes and bones. Reported risk factors associated with metastatic disease are: male gender, pain, symptoms of less than 5 years’ duration and histologic feature of squamous differentiation [8]. We report a rare case of adamantinoma metastatic to the lung with documented overexpression of c-kit, PDGFR-beta and VEGF-R, and responding to tyrosine kinase inhibitor.

Endometrial microcalcifications detected by ultrasonography: clinical associations, histopathology, and potential etiology.

Summary Endometrial microcalcifications are uncommon, with alleged clinical implications ranging from innocuous to ominous. We reviewed the histopathologic slides from 29 patients who had endometrial echogenic foci on pelvic ultrasound and found many endometrial microcalcifications. The extent of microcalcifications in each specimen was graded on a semiquantitative scale from 0 to 3. The mean patient age was 54 years (range, 34-81 years). The specimens included endometrial biopsies, curettages, and hysterectomies. Most of the patients had presented with abnormal vaginal bleeding. Fifteen patients (51.7%) were postmenopausal, 10 (34.5%) were premenopausal, and the rest were perimenopausal. The most frequent endometrial types were atrophic (39.5%), inactive (23.3%), and proliferative (14%). Six specimens (14%) showed benign endometrial polyps. One patient had well-differentiated endometrioid carcinoma of the endometrium without myometrial invasion. Specimens from 16 patients (55.2%) had microcalcifications. The patients with calcifications were older than those without calcifications (mean age, 60 vs. 47 years, respectively; P = 0.017). The extent of microcalcifications positively correlated with the presence of endometrial polyps (P = 0.00076), postmenopausal state (P = 0.004), atrophic endometrium (P = 0.002), and hormone replacement therapy (P = 0.013). The microcalcifications were concentric or amorphous, intraglandular or stromal. They were focally associated with minute papillary epithelial projections or with degenerated endometrial glands. Follow-up was available on 26 patients (89.7%). Except for the patient with endometrioid carcinoma, none has developed uterine, adnexal, or peritoneal malignancy. In summary, endometrial microcalcifications are histologically heterogeneous and are associated with older patient age, postmenopausal state, atrophic endometrium, and endometrial polyps. Those found incidentally by means of pelvic ultrasonography, in our experience, did not portend malignancy.