Urachal mixed adenocarcinoma and small cell neuroendocrine carcinoma with widespread metastasis and resistance to chemotherapy: a case report.

Neuroendocrine carcinoma arising from the urachus is extremely rare. We describe a case of a 33-year-old gentleman who presented with hematuria and diagnosed to have a composite adenocarcinoma and small cell neuroendocrine carcinoma arising from the urachus. The patient also had widespread metastasis at the time of presentation, therefore, he was referred for chemotherapy. However, the disease showed progression despite treatment. Recognition of neuroendocrine carcinoma component in urachal tumors, although rare, is very essential as this histologic type carries poor prognosis with aggressive clinical outcome.

Role of SMARCA4 (BRG1) and SMARCB1 (INI1) in Dedifferentiated Endometrial Carcinoma With Paradoxical Aberrant Expression of MMR in the Well-Differentiated Component: A Case Report and Review of the Literature.

INTRODUCTION: Dedifferentiated endometrial carcinoma is an uncommon highly aggressive uterine tumor. It comprises 2 components: a well-differentiated, low-grade epithelial carcinoma and an undifferentiated carcinoma. The undifferentiated carcinoma frequently exhibits rhabdoid cytologic features. Many of these tumors are characterized by an aberrant switch/sucrose non-fermenting (SWI/SNF) complex. They may also exhibit aberrant expression of mismatch repair (MMR) proteins. Together, these play an important role in the pathogenesis and aggressive nature of the tumor. MATERIAL AND METHODS: We present a case of dedifferentiated endometrial carcinoma in a 63-year-old female showing loss of expression of SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily A, member 4 (SMARCA4/BRG1), and aberrant expression of MMR proteins. We also review the literature starting from the earliest recognition of this entity and the various studies done to explain its molecular pathogenesis and prognostic importance. RESULTS AND CONCLUSIONS: Recognition of SWI/SNF complex-deficient dedifferentiated endometrial carcinoma is important as these tumors do not respond to platinum-based chemotherapy, and consideration of alternative therapies is often necessary. We also want to emphasize that though most of the studies have found MMR deficiency in the undifferentiated carcinoma component, it may be seen only in the low-grade, well-differentiated component, as observed in this case.

Combination of Pembrolizumab With Platinum-containing Chemotherapy for Pleomorphic Carcinoma of the Lung.

BACKGROUND/AIM: Pleomorphic carcinoma of the lung is a rare, highly malignant subtype of lung cancer, with a more aggressive clinical course compared with other types of non-small-cell lung cancer (NSCLC). Platinum-containing chemotherapy has been the standard therapy for patients with NSCLC and pembrolizumab is one of the novel and reliable agents for these patients. CASE REPORT: We herein report the case of a 60-year-old man with advanced chemo-naïve pleomorphic carcinoma of the lung who was successfully treated with a combination of pembrolizumab with platinum-containing chemotherapy. CONCLUSION: In the absence of definitive clinical trials, which are unlikely to be performed due to the rarity of this tumor, our case demonstrates the potential utility of the combination of pembrolizumab with platinum-containing chemotherapy. Our result also suggest that this combination of therapy may be key to the treatment of pleomorphic carcinoma of the lung.

The Immunosuppressive Niche of Soft-Tissue Sarcomas is Sustained by Tumor-Associated Macrophages and Characterized by Intratumoral Tertiary Lymphoid Structures.

PURPOSE: Clinical trials with immune checkpoint inhibition in sarcomas have demonstrated minimal response. Here, we interrogated the tumor microenvironment (TME) of two contrasting soft-tissue sarcomas (STS), rhabdomyosarcomas and undifferentiated pleomorphic sarcomas (UPS), with differing genetic underpinnings and responses to immune checkpoint inhibition to understand the mechanisms that lead to response. EXPERIMENTAL DESIGN: Utilizing fresh and formalin-fixed, paraffin-embedded tissue from patients diagnosed with UPS and rhabdomyosarcomas, we dissected the TME by using IHC, flow cytometry, and comparative transcriptomic studies. RESULTS: Our results demonstrated both STS subtypes to be dominated by tumor-associated macrophages and infiltrated with immune cells that localized near the tumor vasculature. Both subtypes had similar T-cell densities, however, their in situ distribution diverged. UPS specimens demonstrated diffuse intratumoral infiltration of T cells, while rhabdomyosarcomas samples revealed intratumoral T cells that clustered with B cells near perivascular beds, forming tertiary lymphoid structures (TLS). T cells in UPS specimens were comprised of abundant CD8+ T cells exhibiting high PD-1 expression, which might represent the tumor reactive repertoire. In rhabdomyosarcomas, T cells were limited to TLS, but expressed immune checkpoints and immunomodulatory molecules which, if appropriately targeted, could help unleash T cells into the rest of the tumor tissue. CONCLUSIONS: Our work in STS revealed an immunosuppressive TME dominated by myeloid cells, which may be overcome with activation of T cells that traffic into the tumor. In rhabdomyosarcomas, targeting T cells found within TLS may be key to achieve antitumor response.

Acute liver injury leading to death in the setting of brentuximab vedotin monotherapy.

A 67-year-old man with an 11-year history of composite lymphoma was admitted with fevers in the context of neutropenia and acute liver injury, 4 months after the commencement of single-agent brentuximab vedotin. Fevers resolved with intravenous antibiotics, however, his liver function tests remained abnormal and he continued to be deeply jaundiced over the course of his 3-week illness. A liver screen failed to indicate a cause for his liver function test abnormalities and two separate liver biopsies were suggestive of drug-induced liver injury. There was no evidence on biopsy of lymphoma. After consultation with two hepatologists, trials of steroids and ursodeoxycholic acid were unsuccessful. Twenty-five days into admission, he became septic with a normal peripheral blood count and deteriorated rapidly. After discussion with the family, he was deemed not to be for further escalation of care, and he died within several hours. This report summarizes the evidence in relation to hepatotoxicity of brentuximab vedotin.

Efficacy of mesna, doxorubicin, ifosfamide, and dacarbazine (MAID) in patients with advanced pulmonary pleomorphic carcinoma.

OBJECTIVES: Pulmonary pleomorphic carcinoma (PC) is a rare type of lung tumor with a dismal prognosis. There is no consensus on a chemotherapy regimen for PC, and conventional platinum-based chemotherapy has been associated with disappointing response rates and PFS. In searches for a new regimen, the sarcomatoid (spindle or giant cell) component has been assumed to be susceptible to chemotherapy used for soft tissue sarcoma. MATERIALS AND METHODS: The medical records of 17 patients who received mesna, doxorubicin, ifosfamide, and dacarbazine (MAID) for advanced PC between January 2010 and February 2017 were retrospectively analyzed for clinicopathological features and outcomes. RESULTS AND CONCLUSION: The median age was 59 years. Sixteen patients were male, and only one patient had never smoked. Six patients achieved partial response to MAID, leading to an objective response rate of 35%. The median PFS was 2.8 months, and the median OS was 8.7 months. Hematologic toxicity-related adverse events were the most frequent, which comprised grade 3-4 anemia in 35% of patients, neutropenia in 47%, thrombocytopenia in 24%, and febrile neutropenia in 29%. No febrile neutropenia was reported in patients who received 5-day granulocyte-colony stimulating factor (G-CSF) prophylaxis. Most adverse events resolved without complications, except for one death due to sepsis. MAID is an effective, and possibly important, regimen for PC. MAID could be more safely used in clinical practice with appropriate dose modifications and G-CSF primary prophylaxis according to patients' status.

Biallelic tumour suppressor loss and DNA repair defects in de novo small-cell prostate carcinoma.

Small-cell prostate carcinoma (SCPC) is an aggressive malignancy that is managed similarly to small-cell lung cancer. SCPC can evolve from prostate adenocarcinoma in response to androgen deprivation therapy, but, in rare cases, is present at initial cancer diagnosis. The molecular aetiology of de novo SCPC is incompletely understood, owing to the scarcity of tumour tissue and the short life-expectancy of patients. Through a retrospective search of our regional oncology pharmacy database, we identified 18 patients diagnosed with de novo SCPC between 2004 and 2017. Ten patients had pure SCPC pathology, and the remainder had some admixed adenocarcinoma foci, but all were treated with first-line platinum-based chemotherapy. The median overall survival was 28 months. We performed targeted DNA sequencing, whole exome sequencing and mRNA profiling on formalin-fixed paraffin-embedded archival tumour tissue. We observed frequent biallelic deletion and/or mutation of the tumour suppressor genes TP53, RB1, and PTEN, similarly to what was found in treatment-related SCPC. Indeed, at the RNA level, pure de novo SCPC closely resembled treatment-related SCPC. However, five patients had biallelic loss of DNA repair genes, including BRCA1, BRCA2, ATM, and MSH2/6, potentially underlying the high genomic instability of this rare disease variant. Two patients with pure de novo SCPC harboured ETS gene rearrangements involving androgen-driven promoters, consistent with the evolution of de novo SCPC from an androgen-driven ancestor. Overall, our results reveal a highly aggressive molecular landscape that underlies this unusual pathological variant, and suggest opportunities for targeted therapy strategies in a disease with few treatment options. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Contrast-Enhanced Spectral Mammography is Comparable to MRI in the Assessment of Residual Breast Cancer Following Neoadjuvant Systemic Therapy.

PURPOSE: To evaluate the performance of contrast-enhanced spectral mammography (CESM) compared to MRI in the assessment of tumor response in breast cancer patients undergoing neoadjuvant systemic therapy (NST). METHODS: The institutional review board approved this study. From September 2014 to June 2017, we identified patients with pathologically confirmed invasive breast cancer who underwent NST. All patients had both CESM and MRI performed pre- and post-NST with pathological assessment after surgical management. Size of residual malignancy on post-NST CESM and MRI was compared with surgical pathology. Lin concordance and Pearson correlation coefficient were used to assess agreement. Bland-Altman plots were used to visualize the differences between tumor size on imaging and pathology. RESULTS: Sixty-five patients were identified. Mean age was 52.7 (range 30-76) years. Type of NST included chemotherapy in 53 (82%) and endocrine therapy in 12 (18%). Mean tumor size after NST was 14.6 (range 0-105) mm for CESM and 14.2 mm (range 0-75 mm) for MRI compared with 19.6 (range 0-100) mm on final surgical pathology. Equivalence tests demonstrated that mean tumor size measured by CESM (p = 0.009) or by MRI (p = 0.01) was equivalent to the mean tumor size measured by pathology within - 1 and 1-cm range. Comparing CESM versus MRI for assessment of complete response, the sensitivity was 95% versus 95%, specificity 66.7% versus 68.9%, positive predictive value 55.9% versus 57.6%, and negative predictive value 96.7% versus 96.9% respectively. CONCLUSIONS: CESM was comparable to MRI in assessing residual malignancy after completion of NST.

Gemcitabine plus platinum-based chemotherapy for first-line treatment of hepatocholangiocarcinoma: an AGEO French multicentre retrospective study.

BACKGROUND: Hepatocholangiocarcinoma (cHCC-ICC) is a rare liver tumour for which no data on chemosensitivity exist. The aims of this multicentre study were to evaluate overall survival (OS), progression-free survival (PFS), and prognostic factors in cHCC-ICC treated by gemcitabine plus platinum as first-line. METHODS: Unresectable cHCC-ICC treated by gemcitabine plus platinum-based chemotherapy between 2008 and 2017 were retrospectively analysed. Diagnosis was based on histology or, in case of ICC or HCC histology, on discordant computerised tomography scan enhancement patterns associated with discordant serum tumour marker elevation suggesting the alternative tumour. OS and PFS were evaluated by Kaplan-Meier method and prognostic factors by Log-rank test and Cox model. RESULTS: Among 30 patients included, cHCC-ICC was histologically proven in 22 (73.3%). 18 (60%) received gemcitabine plus oxaliplatin (GEMOX), 9 (30%) GEMOX plus bevacizumab, and 3 (10%) gemcitabine plus cisplatin. RECIST criteria were reported in 28 patients: 8 (28.6%) showed partial response, 14 (50%) stable disease, and 6 (21.4%) tumour progression at first evaluation. Median PFS and OS were 9.0 and 16.2 months, respectively. Serum bilirubin ⩾30 µmol l-1 (P=0.001) and positive serology for HBV and/or HCV (P=0.014) were independent poor prognostic factors for OS. CONCLUSIONS: Gemcitabine plus platinum-based chemotherapy is effective as first-line for advanced cHCC-ICC.

Nonchoriocarcinomatous Trophoblastic Tumors of the Testis: The Widening Spectrum of Trophoblastic Neoplasia.

Tumors of trophoblastic derivation other than choriocarcinoma are very rare in the testis but have been reported on occasion in association with other germ cell tumors. Their morphologic spectrum is analogous to the trophoblastic tumors of the female genital tract including epithelioid trophoblastic tumor (ETT) and placental site trophoblastic tumor (PSTT). Herein we report our experience with 8 cases of trophoblastic tumors of testicular origin that lacked the features of choriocarcinoma; these included 4 ETTs, 1 PSTT, 1 unclassified trophoblastic tumor (UTT), 1 partially regressed choriocarcinoma with a monophasic morphology, and 1 hybrid tumor showing a mixture of adenocarcinoma and a UTT. All tumors occurred in young men 19 to 43 years old. Five arose de novo within the testis (2 ETTs, 1 UTT, 1 regressing choriocarcinoma, and the hybrid tumor) as a component of mixed germ cell tumors, and 3 (2 ETTs and 1 PSTT) were found in metastatic sites after chemotherapy. The trophoblastic component was minor (5% to 10%) in 6 tumors but was 95% of 1 metastatic tumor (ETT) and 50% of the hybrid tumor. Other germ cell tumor elements were identified in all cases, most commonly teratoma. The ETTs consisted of nodules and nests of squamoid trophoblast cells showing abundant eosinophilic cytoplasm, frequent apoptotic cells, extracellular fibrinoid material, and positivity for p63 and negativity for human placental lactogen (HPL). The PSTT showed sheets of discohesive, pleomorphic, mononucleated trophoblast cells that invaded blood vessels with fibrinoid change and were p63 negative and HPL positive. The UTT showed a spectrum of small and large trophoblast cells, some multinucleated but lacking distinct syncytiotrophoblasts, and was patchily positive for both p63 and HPL. The hybrid tumor had ETT-like and adenocarcinomatous areas that coexpressed inhibin and GATA3 but were negative for p63 and HPL, leading to classification of the trophoblastic component as UTT. Seven of the patients were alive and well on follow-up (8 to 96 mo; median, 39 mo), whereas the patient with the hybrid tumor died of liver metastases at 2 years. Our study verifies that trophoblastic neoplasms often having the features of nonchoriocarcinomatous gestational trophoblastic tumors may arise from the testis, occur either in the untreated primary tumor or in metastases after chemotherapy, and should be distinguished from choriocarcinoma given what appears to be a less aggressive clinical course.

Human epidermal growth factor receptor 2 expression in mixed gastric carcinoma.

AIM: To investigate human epidermal growth factor receptor 2 (HER2) amplification and protein expression in mixed gastric carcinoma. METHODS: Fluorescence in situ hybridization and immunohistochemistry were used to detect HER2 amplification and protein expression in 277 cases of mixed gastric carcinoma. Protein staining intensity was rate as 1+, 2+, or 3+. RESULTS: Of the 277 cases, 114 (41.2%) expressed HER2 protein. HER2 3+ staining was observed in 28/277 (10.1%) cases, 2+ in 37/277 (13.4%) cases, and 1+ in 49/277 (17.7%) cases. A HER2 amplification rate of 17% was detected, of which 25/28 (89.3%) were observed in the HER2 3+ staining group, 17/37 (45.9%) in 2+, and 5/49 (10.2%) in 1+. Of the 47 patients with HER2 amplification who received chemotherapy plus trastuzumab, 22 demonstrated median progression-free and overall survivals of 9.1 mo and 16.7 mo, respectively, which were significantly better than those achieved with chemotherapy alone (5.6 mo and 12.1 mo, respectively) in 19 previously treated patients (Ps < 0.05). CONCLUSION: HER2 detection in mixed gastric carcinoma displays high heterogeneity. Relatively quantitative parameters are needed for assessing the level of HER2 amplification and protein expression.

Clinicopathological analysis of pleomorphic carcinoma of the lung: diffuse ZEB1 expression predicts poor survival.

OBJECTIVES: Pleomorphic carcinoma (PC) of the lung is a rare epithelial tumor. The clinicopathological characteristics and prognostic factors of PC are controversial. The information on the ZEB1 gene, which crucially impacts survival of patients with other malignant tumors, is limited for PC. MATERIALS AND METHODS: Clinicopathological characteristics of 62 patients with PC were investigated in this study. Associations between immunohistochemical expression of ZEB1 and clinical factors, including patient prognosis, were examined. The patient population consisted of 51 (82.2%) men and 11 (17.8%) women, with a mean age of 65.5 years (range, 31-81 years). RESULTS: The overall survival rate of the 42 patients, for whom follow-up was available, was 68.3% at 5 years. Using TNM criteria, 7 (11.3%), 11 (17.7%), 3 (4.8%), 21 (33.8%), 15 (24.2%), 2 (3.2%), and 3 (4.8%) patients were classified under pathological stage IA, IB, IIA, IIB, IIIA, IIIB and IV carcinomas, respectively. Fifteen (24.1%) patients had tumors consisting entirely of spindle and giant cells (PC component). The other 47 (75.8%) cancers contained additional carcinoma components (i.e., adenocarcinoma (34/62, 54.8%), squamous cell carcinoma (7/62, 11.3%), adenosquamous carcinoma (4/62, 6.5%) and large cell carcinoma (2/62, 3.2%)). Four of 7 (57.1%) stage IA (<20mm) tumors consisted only of spindle and giant cells. ZEB1 expression was observed only in the PC component. Diffuse expression of ZEB1, was defined as positive nuclear staining in ≥75% of cancer cells, and was found in the PC component in 12 patients. Multivariate analysis revealed that lymph node metastasis, pleural invasion, and diffuse ZEB1 expression in the PC component predicted poorer disease-specific survival (p=0.007, 0.022, and 0.016, respectively). CONCLUSION: This is the first report to indicate that ZEB1 may be used as an immunohistochemical prognosticator of PC, which may be useful for histological assessment of PC in biopsy and surgical specimens.

Pancreatic adenocarcinosarcoma of monoclonal origin: a case report.

Adenocarcinosarcoma, a neoplasm containing both carcinomatous and sarcomatous components, is a rare form of a cancer and the pathophysiology is currently poorly understood. Moreover, definitive treatment guidelines for this disease have not yet been established. Pancreatic adenocarcinosarcoma is even more rare and the prognosis is fatal. Here, we report a case of a 77-year-old male with pancreatic adenocarcinosarcoma and metastasis to the liver. The patient presented at our hospital with uncontrolled glucose levels and diabetes mellitus. The patient's laboratory findings were unremarkable with the exception of elevated carbohydrate antigen 19-9 levels. Biopsies of the tumors in the pancreas and the liver revealed two types of tumors: pancreatic adenocarcinoma and a poorly differentiated sarcoma. To determine if KRAS mutations were present, we performed a peptide nucleic acid (PNA) clamp PCR-based assay. DNA sequencing by PNA clamp PCR identified a point mutation in codon 12 of exon 2 within KRAS from both tumor types. Because the KRAS mutation is observed in both tumor components, our findings support a monoclonal tumor origin followed by subsequent divergent differentiation into the sarcomatous and carcinomatous tumor populations. After we considered the patient's status and the late stage of tumor detection, gemcitabine chemotherapy was administered.

Composite hemangioendothelioma and its classification as a low-grade malignancy.

Hemangioendotheliomas are vascular neoplasms occupying a spectrum of biological potential ranging from benign to low-grade malignancy. Composite hemangioendothelioma (CH) is one of the less commonly encountered variants exhibiting a mixture of elements of other hemangioendothelioma subtypes, such as epithelioid, retiform, and spindle cell. Some authors have identified areas histopathologically equivalent to angiosarcoma within CH, raising the question of the true nature of this neoplasm. Although CH recurs locally, there are only 3 reported cases which metastasized. To date, 26 cases (including the present case) have been described in the literature. Herein, we describe a unique case of CH arising in the background of previous radiation therapy and long-standing lymphedema (classically associated with the development of angiosarcoma-Stewart-Treves syndrome) that harbored higher grade areas but behaved as a low-grade malignant neoplasm. This, in conjunction with the many reported cases of CH-harboring angiosarcoma-like areas, and the occasional association with a history of lymphedema, raises the question of whether this variant of hemangioendothelioma may actually be an angiosarcoma that behaves prognostically better than the conventional type. After careful study of the natural disease progression of the current case and review of the literature, we discuss justification for the continued classification of CH as a low-grade malignancy.

Pheochromocytoma with histologic transformation to composite type, complicated by watery diarrhea, hypokalemia, and achlorhydria syndrome.

OBJECTIVE: To describe the rare occurrence of histologic transformation of a pheochromocytoma to a composite type of tumor during a long-term follow-up, which was complicated by watery diarrhea, hypokalemia, and achlorhydria syndrome. METHODS: We report the case of a 12-year-old girl who presented with headache, hypertension, and elevated catecholamine levels in the blood and urine. A tumor was found in the right adrenal gland and resected. When she was 15 years of age, multiple metastatic nodules were found in the lung and liver. Intensive chemotherapy was ineffective, and she underwent follow-up with conservative therapy. At 25 years of age, she complained of diarrhea. Laboratory studies revealed hypokalemia and an increase in the level of serum vasoactive intestinal polypeptide (VIP). A year later, she died of extensive metastatic disease. The primary and recurrent tumors at autopsy were histologically examined. RESULTS: The primary tumor was pure pheochromocytoma, and the tumors at autopsy were a composite type of pheochromocytoma and ganglioneuroma. Only a few VIP-positive cells were found in the primary tumor, whereas both pheochromocytoma and ganglioneuroma cells of composite tumors were frequently positive for VIP. CONCLUSION: Our case showed histologic transformation from pheochromocytoma to a composite type of tumor during a 14-year clinical course, which was associated with additional hormone production and a change in symptoms. Careful attention should be paid to the alteration of endocrine symptoms and hormone levels during prolonged follow-up of pheochromocytoma in young patients.

Fine-needle aspiration biopsy of pleural metastases from a carcinosarcoma or true malignant mixed tumor of the parotid gland mimicking a mesothelioma.

Malignant mixed tumor of the parotid is known to have odd sites for metastases. We describe the fine-needle aspiration cytology (FNAC) findings of pleural metastasis from a malignant mixed tumor misdiagnosed as a mesothelioma on cytology at the onset.A 47-year-old man presented to us with breathlessness and a massive pleural effusion with pleural-based nodules. He had been operated 2 years before for a pleomorphic adenoma of the parotid and had a healthy scar at that site. FNAC from the pleural lesions showed myxoid background substance with entrapped cuboidal epithelial cells with atypical nuclei, which were interpreted as mesothelial cells. These cells in contrast to the usual mesothelial cells were not arranged in sheets but rather were huddled in places and formed a pseudoacinar pattern and blended with the myxoid substance.After the diagnosis of a mesothelioma, patient received pemetrexed and cisplatin based chemotherapy with partial response. While on chemotherapy tumor recurred at the primary site in parotid and was confirmed to be a carcinosarcoma on a FNAC and biopsy.To conclude, pleural metastases from a true malignant mixed tumor of the parotid gland can be misdiagnosed as mesothelioma and could occur in the absence of uncontrolled disease at primary site. Both mesotheliomas and pleomorphic adenomas metastatic to the pleura are biphasic tumors, but in a patient with history of pleomorphic adenoma, the latter should be kept as a foremost possibility. Attention to the cytomorphology of tumor cells will also assist in confirming the diagnosis.

Primary anaplastic pleomorphic xanthoastrocytoma with widespread neuroaxis dissemination at diagnosis--a pediatric case report and review of the literature.

We report a 5 year-old boy with primary anaplastic pleomorphic xanthoastrocytoma (PXA) with whole neuroaxis dissemination at diagnosis who experienced the sudden onset of generalized convulsion. Head- and spinal magnetic resonance imaging (MRI) showed widespread gadolinium (Gd)-enhanced lesions extending to the bilateral frontal- and medial temporal lobes and the spinal cord. Subsequent MRI study demonstrated that the lesion size increased without any neurological deterioration. Under a histopathologic diagnosis of anaplastic PXA he underwent adjuvant chemotherapy consisting of 12 cycles of carboplatin and vincristine. The patient is alive without any neurological deficits; follow-up MRI showed that the lesions remained stable during 18 months of chemotherapy. We report a very rare pediatric case of primary anaplastic PXA with dissemination involving the entire neuroaxis at the time of diagnosis.

Intraabdominal desmoplastic small round cell tumor: results of ifosfamide-based chemotherapy.

Intraabdominal desmoplastic small round cell tumor (IDSRT) is a rare neoplasm, which is malignant and typically occurs in young adults. Although IDSRT is chemotherapy-sensitive, most cases do not achieve a complete response (CR). Even if some cases achieve a CR, they often relapse and result in poor prognosis. We report two cases of IDSRT, in a 24-year-old man and a 23-year-old man, who were treated with ifosfamide-based chemotherapy. Case 1, a 24-year-old man, presented with an abdominal mass, and the diagnosis of the biopsy specimen at laparoscopy was IDSRT. He received 7 courses of ifosfamide-based chemotherapy, which obtained a partial response (PR). He had no surgical resection, except for the biopsy procedure, and he underwent a total of 21 courses of chemotherapy. He died 36 months after diagnosis because of tumor regrowth and peritoneal bleeding. Case 2, a 23-year-old man, whose biopsy material allowed a diagnosis of IDSRT, was treated with 18 courses of chemotherapy, using ifosfamide, that resulted in a PR. This was followed by resection of the abdominal lesions, and he received an additional 2 courses of adjuvant chemotherapy. Four months after, completion of these 2 courses, the tumor recurred, and he died of diffuse pulmonary metastasis 36 months after diagnosis. This case report examines the results of ifosfamide-based chemotherapy in our two patients.

Pharmacokinetics of irinotecan and its metabolites SN-38 and APC in children with recurrent solid tumors after protracted low-dose irinotecan.

Irinotecan (IRN), a topoisomerase I interactive agent, has significant antitumor activity in early Phase I studies in children with recurrent solid tumors. However, the disposition of IRN and its metabolites, SN-38 and APC, in children has not been reported. Children with solid tumors refractory to conventional therapy received IRN by a 1-h i.v. infusion at either 20, 24, or 29 mg/m2 daily for 5 consecutive days for 2 weeks. Serial blood samples were collected after doses 1 and 10 of the first course. IRN, SN-38, and APC lactone concentrations were determined by an isocratic high-performance liquid chromatography assay. A linear four-compartment model was fit simultaneously to the IRN, SN-38, and APC plasma concentration versus time data. Systemic clearance rate for IRN was 58.7 +/- 18.8 liters/h/m2 (mean +/- SD). The mean +/- SD ng/ml x h single-day lactone SN-38 area under the concentration-time curve (AUC(0-->6) was 90.9 +/- 96.4, 103.7 +/- 62.4, and 95.3 +/- 63.9 at IRN doses of 20, 24, and 29 mg/m2, respectively. The relative extent of IRN conversion to SN-38 and metabolism to APC measured after dose 1 were 0.49 +/- 0.33 and 0.29 +/- 0.17 (mean +/- SD). No statistically significant intrapatient difference was noted for SN-38 area under the concentration-time curve. Large interpatient variability in IRN and metabolite disposition was observed. The relative extent of conversion and the SN-38 systemic exposure achieved with this protracted schedule of administration were much greater than reported in adults or children receiving larger intermittent doses.