Thigh mass in a patient with malignant pleural mesothelioma: Metastasis at an unusual site.

Soft tissue tumors are a highly heterogeneous group of lesions with varied clinical presentation. The majority is primary tumors and metastatic tumors are very rare. Malignant pleural mesothelioma presenting as a soft tissue mass at a distant site is even rarer and can cause diagnostic challenges both clinically and pathologically. We report a case of malignant pleural mesothelioma presenting as a soft tissue mass in the left thigh. A 59-year-old man, non-smoker, working in a cement factory since 30 years presented with complains of difficulty in walking since 1½ months. Review of his previous medical records revealed malignant pleural mesothelioma, which was diagnosed 9 months before. He had denied chemotherapy and was on Ayurvedic medication. The lesion involved the adjacent intercostal muscles. Few enlarged lymph nodes were noted in mediastinal and cervical regions. Biopsy of left supraclavicular and right cervical lymph nodes showed metastases. Metastasis from malignant pleural mesothelioma to the thigh was confirmed by immunohistochemistry. The tumor was positive for CK5/6, CK7, Calretinin and vimentin and immunonegative for CEA, Napsin A and TTF 1.

Skeletal muscle metastasis from a gastrointestinal stromal tumor: A case report.

RATIONALE: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. Common sites for metastasis are the liver and peritoneum, whereas skeletal muscle metastases are rare. PATIENT CONCERNS: A 59-year-old man with skeletal muscle metastasis was diagnosed during a period of adjuvant imatinib therapy following the recurrence of GIST of the small intestine. DIAGNOSIS: The patient was diagnosed with skeletal muscle metastasis of GIST based on immunohistochemistry and molecular pathology analysis results. INTERVENTION: Extensive resection of the left thigh tumor was performed. The patient underwent whole-exome sequencing of tissue examination. The results suggest that resistance to imatinib may have been developed, and the patient was therefore administered sunitinib instead. OUTCOMES: Complete remission was observed following sunitinib therapy. LESSONS: In cases of skeletal muscle metastasis diagnosed during a period of adjuvant imatinib therapy following the recurrence of a GIST of the small intestine, whole exome sequencing may be used to discover more gene variations.

A Muscle-Invasive Bladder Cancer Patient With High Tumor Mutational Burden and RB1 Mutation Achieved Bladder Preservation Following Chemotherapy Combined With Immunotherapy: A Case Report.

Neoadjuvant chemotherapy followed by radical cystectomy is the standard of care for patients diagnosed with muscle-invasive bladder cancer (MIBC). However, urinary diversion following radical cystectomy significantly reduces patient quality of life. In addition, patients who significantly respond to neoadjuvant chemotherapy have a strong will to preserve the bladder. Bladder-sparing therapy has become a research focus worldwide. Although the bladder-sparing regimen, referred to as trimodality therapy (TMT), has been accepted, the efficacy of immunotherapy combined with chemotherapy for bladder preservation in patients with MIBC has not yet been published. We describe the case of a 50-year-old male presented intermittent macrohematuria and was diagnosed with bladder urothelial carcinoma by diagnostic transurethral resection of bladder tumor (TURBt) with clinical stage IIIA (cT3bN0M0). A complete response was achieved after four courses of neoadjuvant chemotherapy combined with pembrolizumab. Then, we performed a second TURBt plus randomized biopsy by cystoscopy. The pathology indicated no tumor in the bladder. Adjuvant chemoradiotherapy and immunotherapy were subsequently performed. Imaging examinations, cystoscopy and urine tumor DNA (utDNA) levels were used for surveillance after treatment. Finally, the patient achieved bladder preservation and had remained cancer-free for 19 months at the last follow-up on February 20, 2021. This is the first published case study to describe neoadjuvant chemotherapy plus pembrolizumab followed by concurrent chemoradiotherapy as a novel bladder-sparing regimen and successfully achieved a promising outcome.

Systemic dissemination of tumor cells during transurethral resection in patients with bladder tumor and its clinical relevance: A follow up study.

OBJECTIVE: Tumor cells are shed during transurethral resection of bladder tumor (TURBT) and form the basis for use of single dose immediate chemotherapy instillation to reduce recurrences. Systemic dissemination of these cells along with the irrigation fluid is also possible but not consistently proven. In this study, we evaluated such dissemination of tumor cells into the circulation during TURBT and its clinical impact. METHODS: Patients with primary presentation of bladder tumor who underwent TURBT were included. Peripheral venous blood samples before and after TURBT were analyzed for circulating tumor cells (CTCs) using flow-cytometry. A CD45 negative cell with positive expression of cytokeratin 18, 19, and EpCam was defined as CTC. The CTC counts, pre and post TURBT, were compared and correlated with final histopathology. The patients were also followed up for any local and/or systemic recurrences. RESULTS: Nine (16.98%) out of 53 patients developed a measurable rise in CTCs after TURBT. All of these patients had high grade and muscle invasive disease. Overall, a measurable rise in CTCs was seen in 9 out of 17 (52.94%) patients with muscle invasive disease. There was no difference in the clinico-pathological stage or the status of cystectomy and/or chemotherapy between those who did or did not show a rise in CTCs. On follow up, 7 patients with muscle invasive disease developed local and/or systemic recurrences and the rise in CTCs was not found to be associated with adverse oncological outcomes. CONCLUSIONS: This study confirms the hypothesis of inadvertent dissemination of tumor cells into the circulation during TURBT, especially in patients with high grade and muscle invasive disease. The long-term oncological impact of such dissemination remains to be confirmed.

Gastric adenocarcinoma presenting with multiple skeletal muscle metastases.

A 42-year-old man presented to the gastroenterology clinic with features of gastric outlet obstruction, significant weight loss, anaemia, ascites, and pain in the lower back and left thigh. CT scan of the abdomen and pelvis showed wall thickening in the antropyloric region of the stomach and enhancing soft tissue lesion in the left psoas and right gluteal region. Gastroscopy revealed a circumferential growth in the antrum and pylorus of the stomach, and biopsy from the growth was reported as moderately differentiated adenocarcinoma. Positron emission tomography-CT scan showed multiple skeletal muscle metastases all over the body. Fine-needle aspiration cytology and immunohistochemistry from the psoas lesion confirmed metastatic adenocarcinoma deposits. He underwent antropyloric stenting for his obstructive symptoms and received supportive care, finally succumbed to his illness after 6 weeks.

Ovarian adenocarcinoma with metastases in a white rhinoceros.

A 36-y-old white rhinoceros (Ceratotherium simum) was presented with respiratory distress, sanguineous vaginal exudate, and anorexia. The clinical signs progressed over 40 d, and the rhinoceros died. Autopsy revealed significant ascites; a unilateral, 12.5-cm diameter, polypoid mass in the left ovary; a white, firm transmural mass in the right uterine horn; a white, friable mass in the lung; and white-to-tan, friable small nodules in the diaphragm. Histologic examination revealed similar neoplastic cells in the masses in all 4 locations, composed predominantly of epithelial cells proliferating in a tubulopapillary pattern with significant nuclear atypia and numerous atypical mitotic figures (18-42 per 2.37 mm2). Immunohistochemistry for CK7 (cytokeratin 7) and CK20 (cytokeratin 20) suggest that the ovarian, pulmonary, and diaphragmatic lesions were of ovarian origin and that the ovary was the primary tumor site.

Clinical questions on rehabilitation in cancer patients with skeletal metastasis: a content analysis of the multidisciplinary tumor board records.

PURPOSE: Cancer rehabilitation addresses the functional needs of patients who have various impairments. Disease control is a critical oncological consideration, while physical intervention increased weights of importance in several situations. To identify the clinical status that necessitates active physical intervention in cancer patients with skeletal metastasis, we performed a content analysis in the multidisciplinary tumor board (MDTB) records. METHODS: From January 2017 to September 2019, the MDTB discussed 168 consecutive patients with skeletal metastasis. We reviewed the MDTB records and asked responsible physicians to frame clinical questions. Based on these data, we identified the predictor valuables with the association to rehabilitation-related clinical questions using univariate and multivariate analyses. Moreover, we investigated a predictor of the change in Barthel index (BI) scores using univariate analyses. RESULTS: Rehabilitation-related questions arose more frequently in older patients (p = 0.011), in patients with slow-growth vs. rapid-growth tumor (p = 0.002), and in patients with skeletal-related events (p = 0.001) at MDTB. The tumor growth speed was associated with the change in BI scores, as slower-growth tumors had the benefit of BI gains (p = 0.017). CONCLUSIONS: Regarding rehabilitation in patients with skeletal metastasis, we should pay attention to three parameters: occurrence of skeletal events, patient age, and growth speed of tumors. Rehabilitation-related questions may reflect patients' functional needs that occur more frequently in patients with pathological fractures or neurological symptoms, older patients, and patients with slow-growth tumors.

Surgical excision of a malignant metastatic melanoma located in a skeletal muscle of the lateral thorax of a horse.

BACKGROUND: A 20-year-old grey Warmblood gelding that had history of dermal melanomatosis. OBJECTIVE: To report surgical treatment of a 6-cm large malignant metastatic melanoma located in the cutaneous trunci muscle of the left lateral thorax of a horse. METHODS: A 20-year-old grey Warmblood gelding was referred for evaluation of a large, rapidly growing, thoracic mass. Clinical examination revealed an ovoid, firm, non-painful, movable mass, approximately 6 cm in diameter, located in the cutaneous trunci muscle of the left lateral thorax. Multiple melanocytic nodules were also found at the perianal region and ventral tail. Rectal examination, ultrasonography and endoscopy of the respiratory tract revealed no melanomas internally. Haematological and biochemical values were within normal limits. Surgical excision of both the thoracic mass and perianal nodules was the treatment of choice. Histopathology of the distant thoracic mass confirmed the diagnosis of malignant metastatic melanoma secondary to the perineal lesions that were confirmed as dermal melanomatosis. RESULTS: The horse recovered uneventfully. Up until 3 years post surgery there was no tumour regrowth at the excision sites. CONCLUSION: Surgical excision of the metastatic melanoma was performed and considered successful, with no gross evidence of tumour reoccurrence. Despite the fact that surgical excision is considered a treatment option regarding equine dermal melanomatosis, there is no previously published study proposing surgical removal of distant malignant metastatic melanocytic masses. This is the first report of a successful surgical excision of a large (6 cm) metastatic melanocytic tumour from the skeletal muscle of the lateral thorax of a horse.

Metástasis muscular. Presentación de un carcinoma renal / Muscle metastasis as presentation of kidney cancer / Metástase muscular. Relato de caso de carcinoma renal

Resumen: Introducción: el cáncer de riñón frecuentemente se presenta con metástasis sincrónicas. Son excepcionales los casos comunicados en la literatura donde el diagnóstico de la enfermedad surge a partir de una metástasis muscular. Objetivo: el objetivo del trabajo es presentar un caso clínico de metástasis en músculo deltoides izquierdo como primera manifestación de un carcinoma de células claras de riñón. Caso clínico: paciente de 76 años, sexo masculino, que se operó con diagnóstico de tumoración de región delitoidea izquierda cuyo estudio anatomopatológico informó una metástasis muscular de un carcinoma renal de células claras. Se realizó una tomografía axial computarizada que evidenció una tumoración renal derecha, por lo cual se realizó una nefrectomía que confirmó el diagnóstico del tumor primario. Discusión: el diagnóstico de metástasis muscular de un carcinoma de células claras de riñón, cuando es la primera manifestación de la enfermedad, habitualmente se realiza con el estudio de la pieza de resección quirúrgica o bien a través de una biopsia. Si bien el tratamiento de la metástasis en general es paliativo, el control local de la enfermedad solo es posible cuando se realiza una resección quirúrgica con márgenes libres, ya que otros tratamientos oncológicos no han demostrado ser eficaces.

Summary: Introduction: most kidney cancer patients present with synchronous metastatic disease. A review of the literature reveals cases where the diagnosis is based on muscle metastasis are exceptional. Objective: the study aims to present the clinical case of metastasis to the left deltoid muscle as the initial presentation of renal cell carcinoma. Clinical case: 76 year old male patient who was operated upon diagnosis of tumour in the left deltoid region, the biopsy of which revealed muscle metastasis of clear cell renal cell carcinoma (RCC). Computerized axial tomography evidenced a tumorous formation in the right kidney. The patient underwent right-sided nephrectomy that confirmed the primary tumour diagnosis. Discussion: diagnosis of muscle metastasis of clear cell renal cell carcinoma, being it the initial presentation of the disease, is often done by analysing the surgical resection piece or by means of a biopsy. Despite treatment of metastasis is usually palliative, local control of the disease is only possible when tumour-free margins surgical resection is done, since other oncologic treatments have not proved effective.

Resumo: Introdução: o câncer renal frequentemente se apresenta com metástases sincrônicas. São excepcionais os casos relatados na literatura em que o diagnóstico da doença decorre de uma metástase muscular. Objetivo: o objetivo do trabalho é apresentar um caso clínico de metástase no músculo deltóide esquerdo como primeira manifestação de um carcinoma de células claras do rim. Caso clínico: paciente do sexo masculino, 76 anos, submetido à cirurgia com diagnóstico de tumor na região do deltóide esquerdo, cujo estudo anatomopatológico relatou metástase muscular de carcinoma renal de células claras. Foi realizada tomografia axial computadorizada que revelou tumor renal direito, sendo realizada nefrectomia que confirmou o diagnóstico do tumor primário. Discussão: o diagnóstico da metástase muscular do carcinoma de células claras do rim, quando é a primeira manifestação da doença, geralmente é feito com o estudo da peça de ressecção cirúrgica ou por meio de biópsia. Embora o tratamento das metástases em geral seja paliativo, o controle local da doença só é possível quando a ressecção cirúrgica é realizada com margens livres de patologia, uma vez que outros tratamentos oncológicos não têm se mostrado eficazes.

Treatment patterns and clinical outcomes of chemotherapy treatment in patients with muscle-invasive or metastatic bladder cancer in the Netherlands.

This retrospective study was performed to evaluate real-world oncological outcomes of patients treated with chemo-based therapy for muscle-invasive or metastatic bladder cancer (MIBC/mBC) and compare results to data from RCTs and other cohorts. Among 1578 patients diagnosed, 470 (30%) had MIBC/mBC. Median overall survival (mOS) for RC alone (47 months), first-line (13 months) and second-line (7 months) chemotherapy, and chemotherapy for recurrent disease (8 months) were similar to literature. Treatment with neoadjuvant and induction chemotherapy (NAIC) was only utilized in 9% of patients, and often in patients with poor disease status, resulting in a lower mOS compared to literature (35 and 20 months, respectively). Patients treated with chemotherapy had many adversities to treatment, with only 50%, 13%, 18% and 7% of patients in NAIC, first-line, salvage after RC, and second-line setting completing the full pre-planned chemotherapy treatment. Real-world data shows NAIC before RC is underutilized. Adversities during chemotherapy treatment are frequent, with many patients requiring dose reduction or early treatment termination, resulting in poor treatment response. Although treatment efficacy between RCTs and real-world patients is quite similar, there are large differences in baseline characteristics and treatment patterns. Possibly, results from retrospective studies on real-world data can deliver missing evidence on efficacy of chemotherapy treatment on older and 'unfit' patients.

IL-16 processing in sentinel node regulatory T cells is a factor in bladder cancer immunity.

In the effort of developing new immunotherapies, the sentinel node (SN) has proven a promising source from which to harness an effective antitumour T cell response. However, tumour immune escape, a process in which regulatory T cells (Tregs) play a central role, remains a major limiting factor. Therefore, there is a clear need to increase the knowledge of Treg function and signalling in sentinel nodes. Here, we set out to explore whether the proteome in SN-resident T cells is altered by the tumour and to identify key proteins in SN T cell signalling, focusing on Tregs. Five patients with muscle-invasive urothelial bladder cancer were prospectively included. Mass spectrometry was performed on two patients, with validation and functional studies being performed on three additional patients and four healthy donors. At cystectomy, SN, non-SN lymph nodes and peripheral blood samples were collected from the patients and T cell subsets isolated through flow cytometry before downstream experiments. Proteomic analysis indicated that growth and immune signalling pathways are upregulated in SN-resident Tregs. Furthermore, centrality analysis identified the cytokine IL-16 to be central in the SN-Treg signalling network. We show that tumour-released factors, through activating caspase-3, increase Treg IL-16 processing into bioactive forms, reinforcing Treg suppressive capacity. In conclusion, we provide evidence that Tregs exposed to secreted factors from bladder tumours show increased immune and growth signalling and altered IL-16 processing which translates to enhanced Treg suppressive function, indicating altered IL-16 signalling as a novel tumour immune escape mechanism.

Sonographic Assessment of the Extent of Extrathyroidal Extension in Thyroid Cancer.

OBJECTIVE: This study aimed to determine the sonographic features suggestive of extrathyroidal extension (ETE) of thyroid cancers. MATERIALS AND METHODS: We retrospectively reviewed the sonographic images of 1656 consecutive patients who had undergone thyroidectomy in 2017. The diagnostic performance of sonographic features suggestive of ETE was evaluated using operation and histopathologic reports. Sonographic features for gross ETE to the strap muscle and minor ETE were assessed for thyroid cancer abutting the anterolateral thyroid capsule. Sonographic features for tracheal invasion were assessed according to whether the angle between the tumor and the trachea was an acute, right, or obtuse angle. Sonographic features for recurrent laryngeal nerve (RLN) invasion were assessed based on the association between the tumor and tracheoesophageal groove (TEG) as preserved normal tissue, abutting or protruding into the TEG. RESULTS: ETE was observed in 783 patients (47.3%), including 123 patients with gross ETE (7.4% [strap muscle, n = 97; RLN, n = 24; and trachea, n = 14]) and 660 patients with minor ETE (39.9%). Regarding the diagnosis of gross and minor ETE to the strap muscle, sonographic features of replacement of the strap muscle and capsular disruption showed the highest positive predictive value (75.9% and 58.5%, respectively). Thyroid cancer forming an obtuse angle with the trachea had the highest sensitivity for the diagnosis of tracheal invasion (85.7%), and thyroid cancer protrusion into the TEG showed the highest sensitivity for the diagnosis of RLN (83.3%). CONCLUSION: Sonography is considered beneficial in the diagnosis of ETE to the strap muscle, trachea, and RLN. Assessment of ETE is important for the accurate staging of thyroid cancer, which in turn determines the extent of surgery or whether active surveillance is appropriate or not.

Skeletal Muscle Metastases from Carcinomas: A Review of the Literature.

* Bones are a common site for metastases; however, muscle metastases recently have been more commonly reported, not only as a result of the multidisciplinary approach in the treatment of these patients but also because of more sensitive imaging modalities such as positron emission tomography-computed tomography (PET-CT) that identify these lesions in early stages.* The most common carcinoma is lung carcinoma, with a hematogenous route of spread mainly to the axial region of the body (the psoas muscle, the gluteal muscles, and the paravertebral muscles). * Clinically, skeletal muscle metastases from carcinomas frequently present as painful palpable masses with or without swelling and are commonly found before diagnosis of the primary carcinoma.* Multiple imaging modalities, including radiographs, CT, magnetic resonance imaging (MRI), and PET-CT, have been used for diagnosis and staging, but tissue sampling is needed for a final diagnosis. The most important differential diagnosis of skeletal muscle metastases is with soft-tissue sarcomas.* Treatment is mainly based on chemotherapy and/or radiation; surgery is performed in cases of symptomatic lesions that fail to respond to nonoperative treatment.

Oncoprotein 18 is necessary for malignant cell proliferation in bladder cancer cells and serves as a G3-specific non-invasive diagnostic marker candidate in urinary RNA.

BACKGROUND: Urine-based diagnostics indicated involvement of oncoprotein 18 (OP18) in bladder cancer. In cell culture models we investigated the role of OP18 for malignant cell growth. METHODS: We analyzed 113 urine samples and investigated two human BCa cell lines as a dual model: RT-4 and ECV-304, which represented differentiated (G1) and poorly differentiated (G3) BCa. We designed specific siRNA for down-regulation of OP18 in both cell lines. Phenotypes were characterized by cell viability, proliferation, and expression of apoptosis-related genes. Besides, sensitivity to cisplatin treatment was evaluated. RESULTS: Analysis of urine samples from patients with urothelial BCa revealed a significant correlation of the RNA-ratio OP18:uroplakin 1A with bladder cancer. High urinary ratios were mainly found in moderately to poorly differentiated tumors (grade G2-3) that were muscle invasive (stage T2-3), whereas samples from patients with more differentiated non-invasive BCa (G1) showed low OP18:UPK1A RNA ratios. Down-regulation of OP18 expression in ECV-304 shifted its phenotype towards G1 state. Further, OP18-directed siRNA induced apoptosis and increased chemo-sensitivity to cisplatin. CONCLUSIONS: This study provides conclusive experimental evidence for the link between OP18-derived RNA as a diagnostic marker for molecular staging of BCa in non-invasive urine-based diagnostics and the patho-mechanistic role of OP18 suggesting this gene as a therapeutic target.

Modified Glasgow prognostic score can predict survival of muscle invasive bladder cancer patients after radiotherapy.

In patients with various cancers, modified Glasgow prognostic score (mGPS) before treatment has predicted prognoses after antitumor therapy. This study aimed to assess whether pretreatment mGPS also has predictive value in patients with muscle-invasive bladder cancer (MIBC) after radiotherapy. A retrospective review accumulated 98 consecutive MIBC patients treated with definitive 3D-conformal radiotherapy from January 2011 to December 2016 in a single center. It included cT2-4bN0-3M0 patients with a median age of 79 years (range: 49 to 95 years). Radiotherapy was delivered at 60-66 Gy for bladder cancer. Patients were categorized in terms of their pretreatment serum albumin and C-reactive protein (CRP) values as mGPS_0, mGPS_1, and mGPS_2. Among them, cumulative overall survival (OS) rates were compared by Kaplan-Meier plots with log-rank tests. The number of patients with mGPS_0, mGPS_1, and mGPS_2 were 40, 40, and 18, respectively. The median follow-up time for all patients was 19 months (range: 2-73 months). The 2-year OS rate for all patients was 75.7%. The 2-year OS rates for mGPS_0, mGPS_1, and mGPS_2 were 85.1%, 71.3%, and 60.9%, respectively. Kaplan-Meier curves revealed a significantly higher cumulative OS rate for mGPS_0 compared with mGPS_1 and mGPS_2 (P = 0.003). Using multivariate Cox regression analysis, mGPS_0 and good performance status were associated with favorable OS rates, of which mGPS_0 was more significant (Hazard ratio 2.74, 95% CI 1.30-5.57, P = 0.008). Modified Glasgow prognostic score may be a novel biomarker that can predict survival in patients with MIBC after radiotherapy.

CT imaging features of skeletal muscle metastasis: A rare tumour group with different patterns.

INTRODUCTION: Skeletal muscle metastasis (SMM) are rare and can have different patterns on computed tomography (CT). Our aim was to estimate the frequency of the different patterns, primary tumours and localizations of SMM in a large single-centre sample. METHODS: A retrospective search in the database of our radiological institution was performed for patients with SMM. The primary tumour, affected muscles and CT patterns were estimated. RESULTS: Overall, 104 SMM were diagnosed in 82 patients. In 11 patients (13.4%), SMM were the isolated manifestation of metastatic disease in clinical work up. Regarding primary tumours, gastrointestinal tumours (24.4%), lung cancer (20.4%) and malignant melanoma (13.4%) were identified most frequently. Other malignancies were rare. Most commonly, the trunk musculature was affected (41.3% of the cases). SMM type 1 were identified in 37 cases (35.6%), type 2 in 64 cases (61.5%), type 3 in 2 cases (1.9%) and type 4 in one case (1%). CONCLUSIONS: The present study shows typical imaging appearances of SMM based on a large patient sample in a single centre. SMM has a rare occurrence with several different patterns, which can impose diagnostic difficulties and varies possible differential diagnoses.

[The 478 th case: multiple myalgia with intramuscular nodules].

A 28-year-old man was admitted to the first medical center of Chinese People's Liberation Army General Hospital because of multiple myalgia and intramuscular nodules for more than 2 months. The patient complained of dysphagia, fever and weight loss 2 months ago. Magnetic resonance imaging and biopsy revealed nodular fasciitis. Inflammatory indicators including C-reactive protein, erythrocyte sedimentation rate, platelet count and fibrinogen were slightly elevated. Urine occult blood was positive. Abdominal ultrasound revealed left hydronephrosis. Because nodular fasciitis could not explain the whole situation, a needle biopsy of intramuscular nodules was performed. Pathological examination revealed intramuscular metastatic adenocarcinoma with poor differentiation. Gastric endoscope and positron emission tomography-computed tomography confirmed the diagnosis of advanced gastric adenocarcinoma with extensive metastases of esophagus, lymph nodes, muscles, ureter and bone. Although chemotherapy was given, the patient died of disease progression six months later.