Periprosthetic metastasis following total hip arthroplasty in a patient with lung carcinoma: A case report and review of literature.

RATIONALE: Periprosthetic osteolysis secondary to septic loosening and aseptic loosening is a well-described phenomenon associated with artificial hip arthroplasty. Periprosthetic bone loss as a result of metastatic infiltration is an uncommon cause of early, progressive loosening of joint replacement prosthesis and is rarely described in the literature. PATIENT CONCERNS: The present study describes a 70-year-old male patient who was diagnosed with pulmonary squamous cell carcinoma 5 years after total hip arthroplasty (THA) and developed a metastasis from squamous cell carcinoma in the periprosthetic neosynovial tissue 1 year after formal chemotherapy. The main complaint was hip pain with limited activity for about 3 months. DIAGNOSES: Expansive bone destruction and periprosthetic osteolysis at the right femoral trochanter were identified through X-ray and Tc bone scan. The diagnosis of pulmonary squamous cell carcinoma metastasis was finally confirmed on the basis of postoperative pathological examination. INTERVENTIONS: The patient underwent open surgery with proximal femoral prosthesis revision and tumor prosthesis resection to completely remove the tumor tissue and relieve pain. OUTCOMES: The patient was completely relieved of pain at discharge 2 weeks after surgery and experienced no complications. However, the patient died of respiratory failure due to disease progression 3 months after surgery. LESSONS: We believe that clinicians should maintain a high index of suspicion and consider metastatic disease in differential diagnosis of cases of aseptic loosening, particularly if the patient has a history of malignant disease and the osteolytic lesion involves the outer cortex. In addition, patients with a known history of malignancy should be screened with a pre-operative bone scan to rule out any metastatic infiltration and regularly followed up at short intervals to detect any early bone loss.

[A Subcutaneous Metastasis from Renal Pelvic Carcinoma Growing Rapidly after radical Nephrectomy : A Case Report].

A 78-year-old man was admitted to our department for a right renal mass detected by computed tomography which was accompanied by right hypochondriac pain. Dynamic computed tomography demonstrated a 7cm hypovascular right renal mass invading the liver. No metastatic disease was evident. Transabdominal nephrectomy and partial hepatectomy were performed under the diagnosis of right renal cell carcinoma in July 2014. Pathological examination revealed right renal pelvic carcinoma with liver invasion. After the operation, a subcutaneous nodule in the right forearm rapidly grew in one week. A needle biopsy revealed that it was a metastasis of the urothelial carcinoma. Additionally, lung metastases and lymph node swelling were detected. The patient received two courses of combination chemotherapy (gemcitabine, carboplatin) in August 2014. The subcutaneous metastasis was decreased, but it was not effective for other metastases. Two courses of another combination chemotherapy (methotrexate, vinblastine, epirubicin, calboplatin) were performed. It was effective for all metastatic lesions. During the third course, the patient developed melancholia and rejected additional therapy. He died in March 2015 due to disease progression.

Whole-body (99m)Tc-octreotide scintigraphy with SPECT/CT to detect occult tumor inducing paraneoplastic osteomalacia.

A 32-year-old woman presented with progressive myalgia, bone pain, fatigue, insufficiency hip fractures, high urine phosphate, and low serum phosphate and vitamin D levels. These findings were suggestive of oncogenic osteomalacia. A whole-body Tc-octreotide scintigraphy with SPECT/CT showed uptake on a sclerotic intramedullary lesion in the left medial tibia plateau. MRI depicted a solid lesion. The lesion was surgically removed; the patient became asymptomatic, and follow-up laboratory results normalized. Histopathologic examination revealed a vascular hemangiopericytoma-like tumor, positive for somatostatin receptor (SSR-2). Whole-body Tc-octreotide scintigraphy with SPECT/CT may detect occult oncogenic osteomalacia tumors.

GATA3: a multispecific but potentially useful marker in surgical pathology: a systematic analysis of 2500 epithelial and nonepithelial tumors.

GATA3 is a transcription factor important in the differentiation of breast epithelia, urothelia, and subsets of T lymphocytes. It has been suggested to be useful in the evaluation of carcinomas of mammary or urothelial origin or metastatic carcinomas, but its distribution in normal and neoplastic tissues is incompletely mapped. In this study, we examined normal developing and adult tissues and 2040 epithelial and 460 mesenchymal or neuroectodermal neoplasms for GATA3 expression to explore its diagnostic value in surgical pathology, using monoclonal antibody (clone L50-823) and Leica Bond automated immunohistochemistry. GATA3 was expressed in trophoblast, fetal and adult epidermis, adult mammary and some salivary gland and sweat gland ductal epithelia, urothelia, distal nephron in developing and adult tissues, some prostatic basal cells, and subsets of T lymphocytes. It was expressed stronger in fetal than in adult mesothelia and was absent in respiratory and gastrointestinal epithelia. In epithelial neoplasms, GATA3 was expressed in >90% of primary and metastatic ductal and lobular carcinomas of the breast, urothelial, and cutaneous basal cell carcinomas and trophoblastic and endodermal sinus tumors. In metastatic breast carcinomas, it was more sensitive than GCDFP. Among squamous cell carcinomas, the expression was highest in the skin (81%) and lower in cervical (33%), laryngeal (16%), and pulmonary tumors (12%). Common positivity was found in skin adnexal tumors (100%), mesothelioma (58%), salivary gland (43%), and pancreatic (37%) ductal carcinomas, whereas frequency of expression in adenocarcinomas of lung, stomach, colon, endometrium, ovary, and prostate was <10%. Chromophobe renal cell carcinoma was a unique renal tumor with frequent positivity (51%), whereas oncocytomas were positive in 17% of cases but other types only rarely. Among mesenchymal and neuroectodermal tumors, paragangliomas were usually positive, which sets these tumors apart from epithelial neuroendocrine tumors. Mesenchymal tumors were only sporadically positive, except epithelia of biphasic synovial sarcomas. GATA3 is a useful marker in the characterization of not only mammary and urothelial but also renal and germ cell tumors, mesotheliomas, and paragangliomas. The multiple specificities of GATA3 should be taken into account when using this marker to detect metastatic mammary or urothelial carcinomas.

Phosphaturic mesenchymal tumor, nonphosphaturic variant, causing fatal pulmonary metastasis.

Phosphaturic mesenchymal tumors of the mixed connective tissue type (PMT-MCTs) are rare neoplasms, most of which are benign and cause tumor-induced osteomalacia because of overproduction of a phosphaturic hormone, fibroblast growth factor 23 (FGF23). This entity may have been unrecognized or misdiagnosed as other mesenchymal tumors, such as giant cell tumor, hemangiopericytoma, and osteosarcoma. Ten percent of these tumors, without phosphaturia, were diagnosed only by their histologic features. We report here the first case of malignant PMT-MCT, nonphosphaturic variant, resulting in fatal multiple lung metastases. Chondromyxoid matrix with "grungy" calcification, multinucleated giant cell proliferation, and expression of FGF23 mRNA (reverse transcription-polymerase chain reaction) and fibroblast growth factor 23 protein (immunohistochemistry) were seen in the primary and recurrent tumors of the right foot. The lung metastases showed flocculent calcification and FGF23 protein expression as well as giant cell proliferation. This unique case highlights the need for careful histologic assessment of PMT-MCTs, especially the nonphosphaturic variant, and the need for recognition of its rare malignant behavior.

Advanced prostate cancer as a cause of oncogenic osteomalacia: an underdiagnosed condition.

PURPOSE: Tumor-induced osteomalacia (TIO) is a paraneoplastic bone mineral disturbance related to fibroblast growth factor 23 (FGF23) overproduction by the tumor, usually from mesenchymal origin. Such condition leads to high phosphate renal wasting and, consequently, to cumbersome symptoms as weakness, bone pain, and fractures. METHOD: Case report. RESULT: We report a case of an advanced castration-refractory prostate cancer patient, which developed severe hypophosphatemia with elevated phosphate excretion fraction. TIO was suspected, and increased levels of FGF23 reinforced such diagnosis. The patient died 4 months after being diagnosed with TIO. CONCLUSION: This case suggests that TIO has a dismal prognosis in prostate cancer patients. The clinical oncology community must be aware about such disturbance that can be present in those patients with weakness, bone pain, and hypophosphatemia.

Combination of squamous cell carcinoma-antigen, carcinoembryonic antigen, and carbohydrate antigen 19-9 predicts positive pelvic lymph nodes and parametrial involvement in early stage squamous cell carcinoma of the uterine cervix.

AIM: We examined the correlations between the pretreatment values of four tumor markers (squamous cell carcinoma [SCC]-antigen, carcinoembryonic antigen [CEA], carbohydrate antigen [CA]19-9, and CA125) and postsurgical high-risk factors (parametrial involvement and positive pelvic lymph nodes) in women with SCC of the uterine cervix who had International Federation of Gynecology and Obstetrics clinical stage IB and IIA disease and underwent radical hysterectomy. MATERIAL AND METHODS: In this retrospective study, we reviewed 291 patients between April 1989 and December 2008. The first 200 subjects, studied between 1989 and 2001, served as the training set, and another 91 subjects, studied between 2002 and 2008, comprised the test set. To evaluate the correlations between pretreatment tumor markers and postsurgical high-risk factors, the χ²-test and logistic regression analysis were used for univariate and multivariate analysis, respectively. RESULTS: Multivariate analysis with receiver-operator curves showed that the combination of SCC-antigen, CEA, and CA19-9 strongly predicted postsurgical high-risk factors. Analysis of the training set showed that 66.7% (95% confidence interval, 52.6-84.8%) of patients who tested positive for at least two of these three tumor markers had postsurgical high-risk factors. Similar results were obtained with the test set. CONCLUSIONS: Preoperative levels of SCC-antigen, CEA, and CA19-9 are useful for predicting the status of postsurgical high-risk factors in women with SCC of the uterine cervix who undergo radical hysterectomy.

Development of a brain metastatic canine prostate cancer cell line.

BACKGROUND: Prostate cancer in men has a high mortality and morbidity due to metastatic disease. The pathobiology of prostate cancer metastasis is not well understood and cell lines and animal models that recapitulate the complex nature of the disease are needed. Therefore, the goal of the study was to establish and characterize a new prostate cancer line derived from a dog with spontaneous prostate cancer. METHODS: A new cell line (Leo) was derived from a dog with spontaneous prostate cancer. Immunohistochemistry and PCR were used to characterize the primary prostate cancer and xenografts in nude mice. Subcutaneous tumor growth and metastases in nude mice were evaluated by bioluminescent imaging, radiography and histopathology. In vitro chemosensitivity of Leo cells to therapeutic agents was measured. RESULTS: Leo cells expressed the secretory epithelial cytokeratins (CK)8, 18, and ductal cell marker, CK7. The cell line grew in vitro (over 75 passages) and was tumorigenic in the subcutis of nude mice. Following intracardiac injection, Leo cells metastasized to the brain, spinal cord, bone, and adrenal gland. The incidence of metastases was greatest to the central nervous system (80%) with a lower incidence to bone (20%) and the adrenal glands (16%). In vitro chemosensitivity assays demonstrated that Leo cells were sensitive to Velcade and an HDAC-42 inhibitor with IC(50) concentrations of 1.9 nm and 0.95 µm, respectively. CONCLUSION: The new prostate cancer cell line (Leo) will be a valuable model to investigate the mechanisms of the brain and bone metastases.

Local recurrence and multi-organ metastasis of primary retroperitoneal leiomyosarcoma in unusual locations after surgical resection.

We report a case of retroperitoneal leiomyosarcoma in a 52-year-old woman, who developed local recurrence, pulmonary, hepatic, peritoneal, pancreatic, subcutaneous and intramuscular metastases two years after surgical resection of the primary tumor. Metastasis to the pancreas, subcutaneous or muscular tissue is very rare; however, presence of a lesion in these locations in a known case of leiomyosarcoma might indicate a metastatic tumor deposit.

Prognostic significance of bone or cartilage invasion of locally advanced head and neck cancers.

PURPOSE/OBJECTIVE(S): Locally advanced squamous cell cancers of the head and neck with bone and cartilage invasion (BCI) traditionally have been treated with resection followed up with radiotherapy or less commonly definitive chemoradiotherapy (CRT). However, it is unclear whether bone or cartilage invasion confers a worse prognosis in comparison with each other. MATERIALS/METHODS: T4N0-3M0 squamous cell cancers of the head and neck patients underwent CRT or radical resection followed up with postoperative CRT. Oral cavity, oropharynx, laryngeal and hypopharyngeal squamous cell cancers were included. Radiotherapy ranged from 59.4 to 72 Gy. Concurrent chemotherapy was platinum based. RESULTS: Forty-six patients with BCI were treated. When treated with CRT, 5-year local control was 55% and 43% for BCI, respectively (P = 0.23). Five-year overall survival for these patients was 54% and 29% for BCI, respectively (P = 0.99). When treated with upfront resection, 5-year local control was not significantly different (P = 0.60) nor was 5-year overall survival (P = 0.15). CONCLUSIONS: This study suggests similar outcomes between patients with bone or cartilage invasion treated with upfront CRT or resection followed by CRT. Concurrent CRT may be viable alternative to resection in patients with either bone or cartilage invasion.

Uterine leiomyosarcoma metastatic to soft tissue of the flank following a ten-year disease-free interval.

A 52-year-old female presented with a metastatic uterine leiomyosarcoma to the left flank ten years following total abdominal hysterectomy for a left adnexal primary. Due to the location of the metastasis in the subcutaneous tissue, it was initially felt to be a lipoma. Following excision, pathology revealed leiomyosarcoma. Rarely do uterine leiomyosarcomas metastasize to areas such as the flank or skeletal muscle. We report the case of a uterine leiomyosarcoma metastasis to soft tissue following an extended disease-free interval. With most recurrences occurring within 8 to 16 months following hysterectomy, this case offers an atypical recurrence of this malignancy. The patient's three-year postoperative course has been uneventful.

Long-term survival in stage IV melanoma after repetitive surgical therapy.

BACKGROUND: Surgical therapy in patients with stage IV melanoma is controversial and always an individual decision. CASE REPORT: We report the case of a young melanoma patient, who underwent resection of 5 distant metastases from 4 different organ systems. Thereby, the patient achieved a stable state of disease and a good quality of life for up to now 67 months without any evidence for further tumor manifestations at present. A systemic chemo- or immunotherapy was never applied. CONCLUSION: In selected patients with stage IV melanoma, surgery alone can provide long-term survival with good quality of life.

Cutaneous and subcutaneous metastases of adenocarcinoma of the colon and rectum.

INTRODUCTION: The interesting topic of cutaneous and subcutaneous metastasis from rectal carcinoma is discussed using 3 cases. CLINICAL PICTURE: The first case was a 70-year-old man with T3N2M0 rectal mucinous adenocarcinoma, who developed an inflammatory subcutaneous metastasis at the left scapula 2 years after anterior resection. The second case was a 51-year-old man with T4N2M0 splenic flexure mucinous adenocarcinoma, who developed metastatic disease including a subcutaneous secondary to the back. The third case was a 53-year-old woman who developed vulval recurrence 10 months after abdomino-perineal resection for a low T3N1M0 rectal adenocarcinoma. TREATMENT: All underwent wide resection. CONCLUSION: This entity is rare and usually signifies disseminated disease if found remote from the resection site and warrants a thorough metastatic work up. A high index of suspicion is recommended when encountered with unresolving skin lesions in cancer patients.

Malignant neoplasm of perivascular epithelioid cells of the liver.

Neoplasms of perivascular epithelioid cells (PEComas) have in common the coexpression of muscle and melanocytic immunohistochemical markers. Although this group includes entities with distinct clinical features, such as angiomyolipoma, clear cell sugar tumor of the lung, and lymphangioleiomyomatosis, similar tumors have been documented in an increasing diversity of locations. The term PEComa is now generally used in reference to these lesions that are not angiomyolipomas, clear cell sugar tumors, or lymphangioleiomyomatoses. While most reported PEComas have behaved in a benign fashion, malignant PEComas have occasionally been documented. We present a case of hepatic PEComa with benign histologic features, which nonetheless presented with metastases to multiple sites nearly 9 years later. This case represents the second documented malignant PEComa of the liver, as well as the longest follow-up of a surviving patient with a malignant PEComa, emphasizing both the need for criteria that more accurately predict the behavior of PEComas and the necessity of long-term follow-up of patients with PEComas.

Feasibility of autonomic nerve-preserving surgery for advanced rectal cancer based on analysis of micrometastases.

BACKGROUND: Autonomic nerve preservation has been advocated as a means of preserving urinary and sexual function after surgery for rectal cancer, but may compromise tumour clearance. The aim of this study was to determine the incidence of micrometastasis in the connective tissues surrounding the pelvic plexus. METHODS: The study included 20 consecutive patients who underwent rectal surgery with bilateral lymph node dissection for advanced cancer. A total of 78 connective tissues medial and lateral to the pelvic plexus and 387 lymph nodes were sampled during surgery. All connective tissue samples and 260 lymph nodes were examined for micrometastases by reverse transcriptase-polymerase chain reaction (RT-PCR) after operation. All patients were followed prospectively for a median of 36.0 months. RESULTS: Of 245 histologically negative lymph nodes, 38 (15.5 per cent) were shown by RT-PCR to harbour micrometastases. However, micrometastases to tissues surrounding the pelvic plexus were detected in only two (3 per cent) of 78 tissues, that is in two of 20 patients. Clinical follow-up showed that the two patients had a poor prognosis owing to distant metastases. CONCLUSION: Autonomic nerve-preserving surgery may be feasible for advanced rectal cancer, but study of more patients positive for micrometastases is required.

Bilateral orbital metastases from a neuroendocrine tumor.

When neuroendocrine tumors metastasize to the orbit, they usually do so as solitary lesions, sometimes involving an extraocular muscle. A 70-year-old woman with a known neuroendocrine tumor had bilateral painful proptosis, orbital soft tissue swelling, and ophthalmoplegia. Imaging showed masses within all the extraocular muscles. Orbital biopsy disclosed metastatic neuroendocrine tumor cells within the connective tissue.