Response to lorlatinib on a patient with ALK-rearranged non-small cell lung cancer harboring 1151Tins mutation with uterine metastasis.

We describe a case of an anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer with development of uterine metastasis after crizotinib and alectinib treatment. Gene analysis from the tissue of uterine metastasis revealed the presence of 1151Tins, which was considered to be a crizotinib and alectinib resistance mutation. Subsequent therapy with the third-generation ALK inhibitor lorlatinib, but not ceritinib, showed antitumor activity for 1 year. The uterus is an uncommon site for metastasis from lung cancer, and our case indicated that serial gene analysis could provide new information about ALK inhibitor resistance.

Uterine metastasis from invasive ductal breast carcinoma: A case report with literature review.

Breast cancer is the leading cause of cancer death in women, and most breast cancer related deaths are due to metastases. Uterine metastases from breast cancer are uncommon and rarely reported in the literature. We described the case of a 50 years-old-woman who developed a uterine metastasis, 6 years after the diagnosis of an invasive ductal breast carcinoma. Indeed, although the patient was asymptomatic, the monitoring imaging examinations, particularly the computed tomography (CT) and the positron emission tomography/computed tomography (PET/CT), showed a myometrial lesion. Non-conservative total hysterectomy was performed. The anatomo-pathological examination revealed a myometrial metastasis from an invasive ductal breast carcinoma. Seventeen months after surgery, the patient had no pelvic recurrence, but lungs and bones metastases progressed despite chemotherapy. In the lack of guidelines of uterine metastases from breast cancer's management, we reviewed the existing literature with the aim to provide a rational framework for clinical presentation, diagnostic approach, histological findings and treatment of this rare and heterogeneous pathology. Uterine metastases of breast cancer are frequently revealed with metrorrhagia. They occur preferentially in tumours with initial lobular carcinoma, initial lymph node involvement and positive hormonal receptors.

Lung adenocarcinoma with EGFR gene mutation metastatic to the uterine cervix: A case report.

INTRODUCTION: The cervix is a rare site of metastasis from advanced lung adenocarcinoma. Driven gene detection is particularly important for the treatment of advanced lung adenocarcinoma. PATIENT CONCERNS: A 49-year-old Chinese female was sent to our hospital because of lumbago and sacroiliac joint pain; she was unable to walk and had vaginal bleeding. The following examinations were performed: imaging, colposcopy, bronchoscopy, immunohistochemistry and next-generation sequencing. DIAGNOSIS: According to the clinical manifestations and the examination results, the diagnosis was lung adenocarcinoma with cervical, brain, adrenal gland and bone metastases. More importantly, EGFR gene mutations (del19) were detected in both the primary lung lesion and uterine cervical biopsy specimen. INTERVENTIONS: Osimertinib was chosen as the first-line treatment. OUTCOMES: Lumbago and sacroiliac joint pain were significantly relieved. The levels of tumor markers decreased. Primary injuries and metastatic sites were significantly reduced. CONCLUSION: Physicians should be alert to the signals of vaginal bleeding and consider that primary lung adenocarcinoma may metastasize to the uterine cervix.

Isolated uterine metastasis from a lung adenocarcinoma.

A 65-year-old woman was referred with an incidental finding of a flurodeoxyglucose-avid uterine lesion, following excision of a local lung adenocarcinoma. MRI had features concerning for an atypical fibroid or smooth muscle tumour of uncertain malignant potential. She underwent a total abdominal hysterectomy and bilateral salpingo-oophorectomy. Histopathology demonstrated a leiomyoma infiltrated with adenocarcinoma consistent with a secondary lesion from the lung cancer. Among the small number of cases of uterine metastases of extra-pelvic primary cancers reported in the literature, those from lung cancers are very rare. Concerning features for an atypical fibroid included the patient's age and postmenopausal status, as well as positron emission tomography and MRI findings. A metastatic secondary cancer was not suspected. Diagnosis was only made after histopathological examination. This case represents a very unusual cause of a uterine mass. It demonstrates the importance of thorough preoperative work-up and accurate histopathological assessment.

Long-term response of metastatic hereditary leiomyomatosis and renal cell carcinoma syndrome associated renal cell carcinoma to bevacizumab plus erlotinib after temsirolimus and axitinib treatment failures.

BACKGROUND: Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is a rare hereditary kidney cancer syndrome in which affected individuals are at risk of skin and uterine leiomyomatosis and kidney cancer. HLRCC-associated kidney cancer is a lethal disease with a highly aggressive behavior, and there is no standard treatment option for metastatic disease. CASE PRESENTATION: Here, we report a 29-year-old patient with a locally advanced HLRCC-assiciated RCC. He was administrated temsirolimus initially, then underwent surgical removal of kidney, retroperitoneal lymph nodes, inferior vena cava and tumor thrombi. Unfortunately, multiple liver metastases were confirmed 1 month after surgery, so axitinib was given but failed immediately. We tried bevacizumab plus erlotinib, which achieved long-term good response lasting more than 18 months. He is alive with disease and maintains bevacizumab plus erlotinib treatment. CONCLUSION: The promising results obtained in this patient suggest that combined bevacizumab plus erlotinib may offer a valid treatment option for advanced HLRCC-associated kidney cancer, even after failures of mTOR inhibitor and/or VEGFR TKI based therapies.

Second primary uterine malignancies after radiation therapy for cervical cancer.

PURPOSE: Radiation exposure has long been established as a risk factor for cancer development. The purpose of this study is to assess the risk of uterine malignancy in patients previously treated for cervical cancer with radiation therapy. METHODS: A population-based cohort of 9092 patients diagnosed with cervical cancer who did not undergo surgery and received radiation therapy between 1973 and 2008 was identified from the Surveillance, Epidemiology and End Results Program database (SEER 9). Patients in this cohort who developed endometrial cancer after treatment of cervical cancer were identified. 55,140 patients with endometrial cancer were also identified. The distribution of the different histologic types of endometrial cancer was determined for each of these cohorts. RESULTS: 54 patients (0.6%) were diagnosed with an endometrial cancer more than 12 months after diagnosis of cervical cancer. The average latency to endometrial cancer diagnosis was 160 months, with a range of 14-374 months. The average age of cervical cancer diagnosis was 52 years and the average age at subsequent endometrial cancer diagnosis was 66 years. Only 40% of the endometrial cancers diagnosed following treatment of cervical cancer were endometrioid. The majority were clear-cell adenocarcinomas (42%), 9% were carcinosarcomas and 5.5% were leiomyosarcomas. Of the 55,140 endometrial cancer patients in the database, a vast majority were endometrioid adenocarcinomas (91%), and only 2.3% clear-cell adenocarcinoma, 2.3% carcinosarcoma and 0.5% leiomyosarcoma. The difference in histologic type distribution between these two cohorts is highly significant (p < 0.01). CONCLUSION: A small proportion of women who receive radiation for cervical cancer go on to develop endometrial cancer. These are predominantly of the more aggressive histologic types when compared to primary endometrial cancers. The latency from cervical cancer diagnosis to endometrial cancer diagnosis is over a decade. In a patient who still has a uterus after receiving pelvic radiation, vaginal bleeding should be investigated.

Radical Cystectomy in Pathological T4a and T4b Bladder Cancer Patients: Is There Any Space for Sub Stratification?

INTRODUCTION: According to TNM staging, pathological T4ab are comprehensive of the invasion of prostate, seminal vesicles, uterus or vagina and pelvic or abdominal wall. However, few data are available on the perioperative and oncological outcomes of specific organ invasion. MATERIALS AND METHODS: A total of 917 consecutive bladder cancer (BCa) patients treated with radical cystectomy (RC) at a single institution between 1990 and 2015 were studies. Cox regression analyses were used to stratify pT4ab according to the site of invasion and survival. RESULTS: Overall, 176 (19.2%) and 40 (4.4%) patients harbored pT4a or pT4b disease. Specifically, 84 (9.2%) patients reported prostate and/or SVI invasion, 62 (6.8%) prostate only, 16 (1.7%) uterus, 14 (1.5%) vaginal, 24 (2.6%) pelvic wall, and 16 (1.7%) abdominal wall invasion. The median follow-up in pT4 patients was 48 months. The 1-year cancer-specific mortality (CSM) rates were 71, 65, 24, 50, 50, and 72%, for vaginal, uterus, prostate only, prostate and/or seminal vesicles, pelvic wall, and abdominal wall invasions, respectively. At multivariable Cox regression, the invasion of prostate only (hazard ratio [HR] 3.53), prostate and/or SVI (HR 4.98), uterus (HR 7.16), vagina (HR 6.12), pelvic (HR 11.81), abdominal (8.36) were associated with adverse CSM. CONCLUSIONS: Our study described the differences in survival related to invasion site in pT4 patients, confirming poor survival expectancies in this subgroup. Patients with prostate invasion only seem to be associated with better survival than those affected by concomitant invasion of seminal vesicles. Uterus and vaginal invasions were associated with poor survival outcomes. Patients Summary: In this study, we looked at the outcome of locally advanced invasive BCa (stage pT4) in patients treated with RC at a tertiary referral hospital. We analyzed the differences in survival related to the specific organ invasion. We confirmed poor survival in this subgroup of patients. Only patients who had prostate invasion only seem to have a better survival.

Identification of genomic copy number variations in lung benign metastasizing leiomyomatosis.

OBJECTIVES: Lung metastasizing leiomyomatosis (LML) is an infrequently diagnosed pathology developed after sexual maturation, commonly preceded by uterine myomas. Symptoms can include difficulties to breathe, cough, dyspnea and pain, because of mechanical obstruction exerted by expanding local growing leiomyomas. Lung leiomyomas are normally detected by imaging studies, but nowadays the precise diagnosis demands histological characterization of biopsies obtained from the affected tissues. The purpose of the present study was to determine the presence of genomic alterations in circulating cells of LML. METHODS: Immunohistochemical characterization of a lung biopsy extracted by thoracoscopy was performed. Pathologic proliferative smooth muscle cells were observed in a major lung metastasizing nodule, with a growing pattern similar to a uterine myoma. The presence of cellular linages different to smooth muscle cells was discarded by testing the presence of a battery of molecular markers. Also, a normal karyotype was determine by GTG-banding cytogenetic study, but a high density microarray analysis revealed six submicroscopic chromosomal regions displaying genomic abnormalities: microduplications were detected on chromosomes 4, 14, 17 and 22; and microdeletions on chromosomes 8 and 10. CONCLUSION: This study remarks the relevance of submicroscopic chromosomal analysis of unusual pathologic conditions such as Benign Metastasizing Leiomyomatosis. This propitiate a better understanding of the molecular basis on the development of the pathology, in order to reckon on minimally invasive diagnostic methods, and to design appropriate treatments.

Lobular breast cancer metastasis to uterus during adjuvant tamoxifen treatment: A case report and review of the literature.

Tamoxifen plays a critical role in the treatment of hormone receptor-positive breast cancer. Despite these great benefits against breast cancer, tamoxifen increases the risk of endometrial pathologies such as endometrial hyperplasia, polyp, and neoplasms because of agonistic effect on endometrial tissues. Therefore, gynecologic follow-up should be carried out during tamoxifen treatment. Uterine tumors are frequently detected as the result of presentation with abnormal uterine bleeding. In addition, genital tract's metastases from distant primary tumors can present with abnormal uterine bleeding. Therefore, it is important to determine whether the uterine mass is metastatic or primary because different treatment modalities are used for them. In this context, breast carcinomas are the most frequent metastatic tumors, particularly invasive lobular carcinoma. Here, we report an invasive lobular carcinoma case that presented with abnormal uterine bleeding while receiving tamoxifen therapy and has metastasize in the uterus.

Metastasizing uterine mullerian adenosarcoma in a young female: Diagnostic enigma.

Uterine adenosarcomas are uncommon tumors. It is a biphasic tumor with both epithelial and mesenchymal component. The epithelial component is benign in nature, and the mesenchymal component is malignant. Metastasis is rare in adenosarcoma. We report a case of adenosarcoma with lymph nodal metastasis. A 20-year-old female presented with history of per vaginal bleeding for 1 month. Per vaginal examination revealed a fungating mass protruding through the cervical os. Ultrasonography and magnetic resonance imaging showed a large intrauterine mass. Biopsy of the mass done at an outside hospital was reported as rhabdomyosarcoma. Hence, she was given one cycle of neoadjuvant chemotherapy. Following this, she had profuse bleeding. Emergency hysterectomy with pelvic lymph nodal dissection was performed. The final histopathology was reported as adenosarcoma. One pelvic lymph node showed metastatic deposit of rhabdomyosarcomatous element. In young females presenting with polypoidal mass, uterine adenosarcoma can be considered in the differential diagnosis.

Uterine Corpus Metastasis From Rectal Adenocarcinoma Detected Using 18F-FDG PET/CT.

We report an unusual case of uterine corpus metastasis from rectal adenocarcinoma detected using F-FDG PET/CT. A 47-year-old woman was diagnosed with rectal adenocarcinoma and treated with surgery and radiochemotherapy 3 years ago. During follow-up, she presented with lower abdomen pain and elevated tumor markers, but ultrasonography findings were unremarkable. We performed an F-FDG PET/CT scan, which showed intense F-FDG avidity in the myometrium of the uterine corpus. Uterine corpus metastasis was suspected, and complementary MRI and diagnostic curettage histopathology confirmed uterine metastasis from rectal adenocarcinoma.

Uterine metastases originating from a pulmonary inflammatory myofibroblastic tumor.

Pulmonary inflammatory myofibroblastic tumor (IMT) is a rare mesenchymal tumor, and is considered an inflammatory pseudotumor. Here, we report of a 37-year-old woman with severe cough and stridor who was diagnosed with primary IMT of the lungs, with adenocarcinoma in situ based on the pathology in December 2012. A year later, transabdominal ultrasonography demonstrated a solid mass in the uterine wall that was initially diagnosed as a leiomyoma. However, postoperative histological examination and immunohistochemical staining revealed it as a uterine metastasis of the lung IMT. One year thereafter, the patient died of the lung tumor.

Uterine metastasis of lung adenocarcinoma under molecular target therapy with epidermal growth factor receptor tyrosine kinase inhibitors: A case report and review of the literature.

A 63-year-old woman presented with abnormal vaginal bleeding. Her disease history was significant, and included advanced lung adenocarcinoma with a deletion mutation in exon 19 of the epidermal growth factor receptor (EGFR) gene, which was managed by concurrent chemoradiotherapy, followed by molecular targeted therapy with tyrosine kinase inhibitors (TKIs) for a two-year period. Contrast-enhanced computed tomography showed the enlargement of a previously suspicious myoma node, with peripheral enhancement. Hemorrhagic necrosis was also observed on magnetic resonance imaging. Transabdominal hysterectomy and bilateral salpingo-oophorectomy showed solitary intramyometrial metastatic lung adenocarcinoma with a second-site T790M gatekeeper mutation in exon 20 of the EGFR gene. In conclusion, uterine metastasis from lung adenocarcinoma can present a diagnostic challenge. The possibility of lung cancer metastasis should be considered when a uterine mass increases in size during treatment. Molecular analysis of the EGFR gene to detect mutations could provide useful information for planning the treatment strategy.

Malignant Female Adnexal Tumor of Probable Wolffian Origin: Case Report and Literature Review.

Although most female adnexal tumors of probable Wolffian origin have a benign biologic behavior, occasional cases have exhibited malignant potential. We encountered a 50-yr-old woman with an uncommon female adnexal tumors of probable Wolffian origin, which involved bilateral ovaries, invaded the ipsilateral fallopian tube, and extended to the uterine serosa. The initial histopathologic presentation caused significant confusion in pathologic diagnosis. Multiple differential diagnoses including ovarian endometrioid carcinoma, Sertoli cell tumor, and metastasis from nongynecologic organs were considered. After careful examination of the histologic findings and a thorough investigation with multiple immunohistochemical stains, the diagnosis was ultimately established. A literature review on female adnexal tumors of probable Wolffian origin including a malignant form is presented.

Uterine Metastasis From Gastric Adenocarcinoma Masquerading as Physiologic Endometrial Uptake in FDG PET/CT.

A 44-year-old woman with newly diagnosed gastric adenocarcinoma by gastroscopy underwent F-FDG PET/CT to evaluate possible metastasis. The images demonstrated intense activity in the region of uterine corpus, as well as greater gastric curvature. Physiologic uptake of endometrium was initially suspected, given the rarity with which extragenital cancers metastasize to the uterus. Ultimately, the endometrium proved to be mucinous adenocarcinoma of gastric origin based on its shared histological features and compatible immunostaining profile.