Is yolk sac tumor related to the pathophysiology of low birthweight?

An 8‐year‐old Japanese girl was admitted with an ovarian yolk sac tumor. Regarding birth history, the patient had been delivered by cesarean section at 25 weeks of gestation with a birthweight of 711g. She had required neonatal intensive care including oxygenation, various medications, and tests. After surgery and chemotherapy, there was no recurrence for 2 years, at the time of writing. Yolk sac tumor, which is a malignant germ cell tumor, is rare in children. Although the cause and risk factors are unclear, it has been reported that malignant germ cell tumors in childhood have been associated with pathophysiology at birth. Given that premature infants are more likely to survive due to advances in perinatal care, it is expected that such cases will increase in the near future. We suggest that children born prematurely require careful follow up.     

Immune profiles of desmoplastic small round cell tumor and synovial sarcoma suggest different immunotherapeutic susceptibility upfront compared to relapse specimens

1 Background

Desmoplastic small round cell tumor (DSRCT) and synovial sarcoma are rare tumors with dismal outcomes requiring new therapeutic strategies. Immunotherapies have shown promise in several cancer types, but have not been evaluated in DSRCT and synovial sarcoma. Because the immune microenvironment can provide indications of the inflammatory nature of tumors, immunohistochemical staining is able to assess the tumor immune infiltrates in both tumor types.

2 Procedure

Using tissue microarrays of DSRCT and synovial sarcoma tumor samples, we detected tumoral HLA‐A/B/C, beta‐2‐microglobulin(B2M), and PD‐L1 expression, and quantified tumor‐infiltrating lymphocytes expressing CD4, CD8, CD56, CD45RO, or FOXP3 by immunohistochemistry. We used staining intensity on a scale of 0–3 and percentage of tumor stained to determine HLA, B2M, and PD‐L1 scores. We calculated the cytotoxic T lymphocyte (CTL) target score as HLA score × B2M score/100.

3 Results

In diagnostic samples, we found high HLA and CTL target scores and low PD‐L1 expression with decreased scores in recurrence for both tumor types. We found an increase in CD56⁺ natural killer cells in DSRCT samples from diagnosis to recurrence.

4 Conclusions

We found similar immunostimulatory profiles in DSRCT and synovial sarcoma. Our findings suggest that DSRCT and synovial sarcoma may be amenable to immunotherapies, albeit there was significant heterogeneity. Interestingly, HLA and CTL target scores decreased at recurrence, possibly reflecting immunoevasion. Our findings suggest both tumor types may be amendable to CTL‐based therapies at diagnosis but less so at relapse. Our results support further investigation into the prognostic and predictive value of these findings in a larger dataset.     

A case of Epstein–Barr virus–associated pulmonary leiomyosarcoma arising five yr after a pediatric renal transplant

Suzuki K, Urushihara N, Fukumoto K, Watanabe K, Wada N, Takaba E. A case of Epstein–Barr virus–associated pulmonary leiomyosarcoma arising five yr after a pediatric renal transplant. Pediatr Transplantation 2011: 15: E145–E148. © 2010 John Wiley & Sons A/S. Abstract: EBV‐associated SMTs in immuno‐compromised patients have recently been reported. We report on a case of EBV‐associated pulmonary leiomyosarcoma arising five yr after renal transplantation. The patient was an eight‐yr‐old girl, who received a living related kidney transplant from her mother. She had had bilateral giant Wilm’s tumors as an infant and underwent bilateral nephrectomy at one and two yr of age. At the age of seven, she suffered from bronchitis several times, and a year later, two nodules were detected in her left lung by X‐ray and computed tomography. We suspected a recurrence of Wilm’s tumor and performed surgical resection. The pathological finding was SMT with moderate mitosis and no evidence of Wilm’s tumor. The fact that the tumors were positive for EBER suggested an association with the EBV. Six months later, there was a recurrence in her left lung. Surgical resection was performed, and immunosuppressive agents were reduced. Two yr after the second operation, she is well with no recurrence. We report the first case of EBV‐associated pulmonary leiomyosarcoma in a pediatric patient after renal transplantation owing to a malignant tumor.     

MRI changes associated with vigabatrin treatment mimicking tumor progression

Vigabatrin has been used as first‐line treatment of infantile spasms. Reversible cerebral MRI signal changes have been reported to be associated with vigabatrin treatments. We report a case of a 5‐month‐old female who, following resection of an anaplastic oligodendroglioma developed, while treated with vigabatrin for seizures, abnormal DWI and FLAIR MRI signal changes worrisome for tumor progression or recurrence. Discontinuation of vigabatrin led to reversal of the MRI changes. This report highlights the fact that vigabatrin treatment can mimic tumor progression on MRI and confound management of tumors associated with seizures in pediatric patients. Pediatr Blood Cancer. 2010;55:1221–1223. © 2010 Wiley‐Liss, Inc.     

Problematic, clinic and treatment of benign bone tumors in childhood and adolescence (author's transl)

Bone tumors in children show a large variety in Kind. Often there is no clear distinction between benign and malignant tumors. So in between according to Zollinger there are semimalignant tumors with potential malignity. Adequate excision of these tumors or resection enbloc inhibit the tumor recurrence and give a good prognosis to semimalignant tumors. 31 children with benign bone tumors were operated between 1972 and 1979. They have been followed up medically and radiologically from 1 to 7 years. Up to now we could neither find a recurrence nor a sign of malignant degeneration.     

Hepatic spindle cell tumors in HIV positive children

Spindle cell tumors (leiomyoma, leiomyosarcoma) have been described in HIV infected children involving the gastrointestinal tract, respiratory tract and liver. The same tumor has been reported in immuno-compromised children following liver and renal transplantation. A case of hepatic spindle cell tumor in an HIV infected child is discussed.     

Angiosarcoma successfully treated with liver transplantation and sirolimus

Malignant liver tumors represent approximately 1% of malignancies in children. HA is a high‐grade tumor of endothelial cells that is even more rare in the pediatric population. HA has a limited response to chemotherapy, radiation and resection with universal tumor recurrence with LT and nearly 100% mortality by 18 months. This is the first reported successful case of hepatic angiosarcoma in a child who was treated by LT in combination with sirolimus. Sirolimus antagonizes the mTOR pathway, which regulates cell proliferation, differentiation, and migration, and is being studied as an anti‐neoplastic agent for solid tumors.     

儿童原发性胸部巨大肿瘤的外科处理

目的 总结儿童原发性胸部巨大肿瘤的治疗经验,探讨更有效的外科治疗方式.方法 对于占据整个胸腔的胸内肿瘤采取胸部正中切口,处理肺门或分离肿瘤;而其他肺肿瘤及后纵隔肿瘤则采取常规后外侧切口行肿瘤根治术.对于前纵隔肿瘤酌情采取胸部正中切口或前外侧切口,锐性加钝性法分离,直至完整切除肿瘤为止.结果 5例术前诊断为肺肿瘤的患儿,2例行左全肺切除,1例行右全肺切除,1例行右中下肺叶切除,病理学诊断均为胸膜肺母细胞瘤;另1例行胸壁肿块大块切除术,免疫组化检查结果显示为＂左胸壁肋骨Ewing肉瘤＂;1例术前诊断为胸腔内巨大肿块患儿行肿块切除后病理报告为软骨肉瘤;4例前纵隔肿瘤中,2例为梭形细胞瘤,另2例来源于胸腺,分别为胸腺瘤和恶性神经鞘瘤,肿瘤均被完整切除;4例后纵隔肿瘤均作肿块切除,病理检查报告均为神经母细胞瘤.结论 手术指征、手术径路的把握及术者的经验直接决定胸部巨大肿瘤患儿的治疗效果.     

Solitary Intestinal Fibromatosis with Perinatal Bowel Obstruction

Three newborn male infants presented with bowel obstruction in the first day of life and at surgery were found to have solitary tumors involving the small or large intestine. Histologic examination in each case showed a transmural infiltrative spindle cell lesion having the morphologic features of fibromatosis. Ultrastructural studies in one case revealed the tumor to be composed of myofibroblasts. The patients are all alive and well without recurrences 26 months to 10 years after surgery. Only 3 previous cases of solitary congenital fibromatosis of the intestinal tract have been reported. Some of the other congenital spindle cell tumors cited in the literature under various names have morphologic and biologic similarities to our cases and may in fact be examples of congenital fibromatosis. The appropriate treatment of this unusual lesion is local excision, and the prognosis is excellent.     

Transmission of clear cell tumor in a graft liver from cadaveric donor: Case report

Backes AN, Tannuri ACA, de Mello ES, Gibelli NEM, de Castro Andrade W, Tannuri U. Transmission of clear cell tumor in a graft liver from cadaveric donor: Case report. Abstract: Neoplasms in children after organ transplantation are related to the type and intensity of immunosuppression and the donor–recipient serostatus, especially in relation to the Epstein–Barr virus. The patient was a two‐yr‐old female child with biliary atresia who underwent a liver transplantation from a female cadaver donor. Two adults received kidney transplants from the same donor. Nine months after transplantation, one of the adult recipients developed an urothelial tumor in the kidney graft. Imaging tests were repeated monthly in the liver‐transplanted child and revealed no abnormalities. However, one yr and two months after the transplantation, the patient developed episodes of fever. At that time, imaging and liver biopsy showed a clear cell tumor of urothelial origin in the graft and the disease was limited to the liver. The patient underwent liver retransplantation, and she is currently free of tumor recurrence. Although rare, the occurrence of tumors in the post‐transplant period from cadaver donors, without previously diagnosed tumors, is one of the many problems encountered in the complex world of organ transplantation.     

Childhood pheochromocytoma in a survivor of central primitive neuroectodermal tumor

Pheochromocytoma and central nervous system primitive neuroectodermal tumor are both neural crest‐derived tumors. The former is usually benign and develops mainly in adulthood and the latter brain tumor mainly occurs in childhood and has a poor prognosis. We report a case of a 15‐year‐old boy who developed pheochromocytoma after more than 10 years of complete remission of central primitive neuroectodermal tumor. Thus far, there have been no reports of childhood cancer survivors who developed pheochromocytoma. This quite rare occurrence of two tumors in a single patient may imply some unidentified linkage or common genetic background.     

Anaplastic sarcoma of the kidney: Case report and literature review

Anaplastic sarcoma of the kidney (ASK) is a relatively newly recognized pediatric renal tumor. The present patient, a 13‐year‐old boy with a large renal mass, underwent surgery. Pathological findings showed proliferation of short spindle‐shaped cells with anaplastic features including multiple foci in hyaline cartilage. Complex chromosomal abnormalities were detected in the tumor cells. Postoperative chemotherapy with the regimen for Ewing's sarcoma achieved complete remission but the tumor recurred and the patient died during re‐induction chemotherapy. Autopsy indicated the cause of death as duodenal hemorrhage. Because there were no viable tumor cells, the recurrent tumor was considered to have been completely cured by chemotherapy. ASK is a very rare tumor, of unknown pathogenesis, and no standard treatment has yet been established, but the tumor cells may be responsive to chemotherapy. Further study is needed to establish the optimal treatment strategy.     

Paraneoplastic opsoclonus myoclonus syndrome associated with inflammatory myofibroblastic tumor in a pediatric patient

Opsoclonus myoclonus syndrome (OMS) is a rare neurological syndrome caused by a paraneoplastic autoimmune process that affects children with neuroblastic tumors. Treatment includes corticosteroids, intravenous gamma globulin (IVIG), rituximab, and other immunosuppressive therapies. Here, we describe a patient diagnosed with OMS associated with a localized inflammatory myofibroblastic tumor. The patient has no evidence of tumor recurrence following surgical resection with 8‐month follow‐up. The neurologic symptoms resolved with corticosteroids and IVIG. This case demonstrates that in children, neoplasms other than neuroblastoma may be associated with this paraneoplastic syndrome, and highlights the importance of evaluating patients with OMS for underlying malignancies.     

Cellular Peripheral Neural Tumors (Neurofibromas) in Children and Adolescents: A Clinicopathological and Immunohistochemical Study

Nine examples of a cellular peripheral neural tumor (CPNT) were identified in a review of 139 peripheral nerve sheath neoplasms in children, which included 60 neurofibromas and 16 malignant peripheral nerve sheath tumors. The mean age at diagnosis of these nine patients was 7 years, with six presenting in the first decade of life and four were noted at birth. The male:female ratio was 0.5. Topographically, the tumors were located in the extremities, 4; head and neck, 3; and trunk, 2. One or another stigmata of von Recklinghausen's neurofibromatosis (VRN) was present in four patients. After initial resection, seven children remained well, but two developed a recurrence; the histology was identical to the original tumor in one case but overt malignant transformation had occurred in the second. This case was the only tumor-related death in this series. The CPN as a circumscribed but nonencapsulated mass measuring 1.8-7.5 cm in greatest dimension in the subcutaneous and deep soft tissues and had a compact spindle cell pattern, occasional mitoses, and minor foci of typical neurofibroma. Immunohistochemical staining revealed vimentin expression in all seven cases, Leu-7 in six, myelin basic protein and S-100 protein in five, desmin in one, and actin in none. In contrast to neurofibroma and malignant peripheral nerve sheath tumors, CPNT tended to occur earlier, either congenitally or in the first decade, and slightly more commonly in females. The anatomical distribution and pattern of immunoreactivity were similar to neurofibroma. However, the cellularity and mitotic activity of these neoplasms were sufficiently disquieting as to raise concerns about the prognosis, and in one case, the tumor behaved in an unequivocally malignant fashion. When a peripheral neural tumor with the pathologic features described in this study is encountered, wide excision and careful clinical follow-up are recommended.     

Ossifying Renal Tumor of Infancy: A Clinicopathologic Study of Nine Cases

We studied nine ossifying renal tumors of infancy (ORTI), including all five previously reported cases. There were eight boys and one girl ranging in age from 6 days to 14 months. Cross hematuria was the presenting sign in all nine patients. Eight tumors arose in the left kidney and six in the upper pole. All seven patients with follow-up information were free of recurrence. All lesions were attached to a renal papilla and presented mainly within the calyceal lumen. Two resembled staghorn calculiclinically. All tumors contained varying proportions of osteoid, osteoblastic cells, and spindle cells. The spindle cell component had features strongly suggesting that they represented hyperplastic intralobar nephrogenic rests (ILNR). The proportion of osteoid and degree of osseous maturation increased with increasing age of the patient. ORTI is a distinctive clinicopathologic entity, possibly representing a distinctive interaction between ILNR in the renal papilla with distal collecting duct or urothelial cells in the developing kidney.     

Effectiveness of chemotherapy in melanotic neurectodermal tumor of infancy

MNTI is an uncommon tumor mainly of infants. Surgery is the primary modality of treatment. Chemotherapy has been tried for recurrent/residual tumors. The chemotherapeutic response of 3 infants treated at a center is discussed here. All 3 infants showed good response to chemotherapy. In 2 of them complete residual tumor resection became possible; 2 of them are alive and tumor regression continues.One child had local recurrence later and was lost for follow-up.     

Gastrointestinal stromal tumors in children and young adults: a clinicopathologic, molecular, and genomic study of 15 cases and review of the literature

Gastrointestinal stromal tumors (GISTs) are mesenchymal tumors of the intestinal tract that typically occur in adults over the age of 40 years. GISTs in younger patients are rare and not well characterized. The objective was to define the characteristics of GISTs in children and young adults (<30 years old). Clinicopathologic and molecular features, including KIT/PDGFRA genotype, in GISTs from 5 children and 10 young adults were analyzed. Gene expression analysis was performed on 5 gastric tumor samples from 2 children, 2 gastric tumors from young adults, and 10 gastric GISTs from older adults using an U133A Affymetrix platform (22,000 genes). All five pediatric GISTs occurred in girls, involved the stomach as multiple nodules, showed predominantly an epithelioid morphology, often involved lymph nodes, and lacked KIT or PDGFRA mutations. Although all five patients developed recurrence (four in the liver, three in the peritoneum, and two in both sites), four are still alive with disease. Of the 10 GISTs in young adults, half occurred in the small bowel and had spindle cell morphology, and one case had lymph node metastasis. KIT mutations were identified in seven cases, four in exon 11 and three in exon 9. Seven patients developed recurrence, and at last follow-up two patients had died of disease. Gene expression analysis showed high expression of PHKA1, FZD2, NLGN4, IGF1R, and ANK3 in the pediatric and young adult versus older adult cases. GISTs that occur in children are a separate clinicopathologic and molecular subset with predilection for girls, multifocal gastric tumors, and wild-type KIT/PDGFRA genotype. In contrast, GISTs in young adults are a more heterogeneous group, including cases that resemble either the pediatric or the older adult-type tumors. The distinct gene expression profile suggests avenues for investigation of pathogenesis and potential therapeutic strategies.     

Sacrococcygeal teratoma

This retrospective study details our experience regarding 72 patients with sacrococcygeal teratoma treated over a period of 17 years. The sex incidence was nearly equal, but there was a high proportion of Altmann type IV tumors. A preliminary colostomy before combined abdominosacral excision of large type III and IV lesions reduced morbidity. Sixty-six percent of the patients presented beyond the neonatal period; 14 had been treated elsewhere for bowel/urinary obstruction. Imaging studies included radiography, abdominal ultrasound, computed tomography, and magnetic resonance imaging (after 1995). In 60 patients the tumor was excised via the sacral route, 11 had a preliminary colostomy, and 1 had a vesicostomy. Eight children (5 with malignant lesions) required abdominosacral excision. After 1990, serial estimation of serum alpha-fetoprotein (AFP) was used to monitor tumor recurrence. There were 34 male and 38 female patients (age range 3 days-12 years); 47 had benign tumors, of which 42 were excised through the sacral route. Three patients underwent a preliminary colostomy and abdominosacral excision of the tumor with subsequent colostomy closure. There were 4 deaths in this group; no recurrence was seen in the surviving children with benign tumors. Twenty-five patients had malignant teratomas. In 18 of these the tumor was excised via the sacral route and 5 underwent abdominal-sacral excision. Eight had a preliminary colostomy and chemotherapy followed by excision of the residual tumor and colostomy closure. None of the initial 14 patients with malignant lesions survived beyond 2 years. Of the latter 11 (who received cisplatinum-based chemotherapy), 10 were alive 1 year after surgery. One patient is currently on preoperative chemotherapy and another developed recurrence of the tumor. The overall follow-up ranged from 3 months to 8 years; there has been no complaint of functional neurological deficit in any of the patients. As intrapelvic tumors tend to have a delayed diagnosis, this can be avoided by performing a rectal examination. There should be no recurrence after excision of a benign teratoma. Cisplatinum-based chemotherapy has improved the survival of patients with malignant tumors.     

Infantile Fibrosarcoma—a Misnomer?

Two cases of congenital or infantile fibrosarcoma are described that were incompletely excised at the time of primary excision and have not recurred or metastasized after 3 years. The tumors were composed of densely cellular spindle cells with a high mitotic index. Immunohistochemical stains were positive for vimentin but negative for desmin and S-100. The tumor cells were grown in vitro, and a karyotype was obtained. Both tumors had normal diploid modal karyotypes. In addition, fragments of the primary tumor from both cases were injected subcutaneously into nude mice; neither tumor could be heterotrans-planted. The clinical course and biologic features of these two tumors suggest that congenital or infantile sarcoma does not have the properties of a malignant neoplasm, and thus the designation of these tumors as a sarcoma may be a misnomer.     

Giant-cell fibroblastoma and dermato fibro sarcoma protuberans: the same tumoral spectrum? Report of two cases of association in children.

We describe two cases of giant-cell fibroblastoma (GCF) with dermato fibro sarcoma protuberans (DFSP) component, occurring in two children in a chest wall localization. One case recurred 1 year later. The two patients were tumor-free 12 and 8 years later. GCF is a rare mesenchymal cutaneous and subcutaneous tumor reported mostly in the first two decades of life. Dermato fibro sarcoma protuberans, occurring preferentially in adults, is a rare skin tumor with a pronounced tendency to local recurrence. Some cases of association of recurrence of GFC under the form of DFSP have been reported, raising the question of a continuum between the two tumors. The treatment of choice of the two tumors is a wide local excision.