Ra Risdon

Clinicopathological features of paediatric deaths due to myocarditis: an autopsy series

Introduction: Myocarditis is a recognised cause of cardiac failure in childhood but the frequency of myocarditis as a cause of sudden unexpected death across the paediatric age range is uncertain. Methods: A structured review of the results of all autopsies carried out in a single paediatric centre over a 10-year period, including the results of all investigations performed as part of the centre’s policy for the post-mortem investigation of paediatric deaths. Results: During the study period there were 1516 autopsies of children aged 0–18 years. Histologically proven myocarditis was present in 28 cases (1.8%, age range 10 days to 16 years, median age 10 months), of which 16 (57%) presented as sudden death. More than half of all cases (54%) occurred in infants less than 1 year of age, accounting for 2% of infant deaths referred for autopsy, compared with around 5% of childhood deaths over the age of 5 years. In almost 40% of cases there were no macroscopic cardiac abnormalities, the diagnosis being entirely dependent on routine histological examination of the heart, and post-mortem heart weight was normal in the majority of cases. Virus was detected in nine (36%) of the 25 cases in whom virological analyses were performed. The histological features were similar in all cases, with an interstitial inflammatory cell infiltrate, predominantly lymphocytic, with focal myocyte necrosis and interstitial oedema. Conclusions: Myocarditis is a rare cause of death in infancy and childhood, and the majority of cases present as sudden unexpected deaths, which require routine histological sampling of the heart for its detection.

Aberrant immunohistochemical expression in nonrhabdomyosarcoma soft tissue sarcomas of infancy: retrospective review of clinical material.

Malignant soft tissue tumors other than rhabdomyosarcoma (RMS) are uncommon in infancy, representing approximately 5% of pediatric sarcomas. The pathological categorization of non-RMS soft tissue malignancies from these young patients is complicated by variation in both morphologic and immunohistochemical features. A search covering an 11-year period identified 19 patients presenting at birth or in infancy with a clinical or referral diagnosis of soft tissue sarcoma. After histologic and immunohistochemical review, nine of these tumors were classified as primitive neuroectodermal tumor (PNET), three as infantile hemangiopericytoma (HPC), two as infantile fibrosarcoma (FS), and five as undifferentiated sarcoma. Those identified as undifferentiated sarcomas showed an atypical spindle and ovoid cell morphology, with cellular pleomorphism and high mitotic rate, but lacking the fascicular growth pattern of classic infantile fibrosarcoma. Immunohistochemical staining in this group showed variable weak positivity for a range of markers (desmin, smooth muscle actin, Myo-D1, PGP, NSE, S100, CO56, cytokeratin, and CD99), and did not fit readily into any distinct diagnostic category. In this series, tumors classified as soft tissue PNETs had a poor prognosis despite aggressive treatment. However, once RMS, PNET, and other rare specific lesions are excluded, the remaining undifferentiated sarcomas, despite their unusual morphology and immunohistochemistry, appear to behave in a similar favorable manner to infantile fibrosarcoma.

Changes in computed tomography features following preoperative chemotherapy for nephroblastoma: relation to histopathological classification

The objective of this study is to assess computed tomography (CT) changes, both volume estimates and subjective features, following preoperative chemotherapy for nephroblastoma (Wilms’ tumour) in patients treated on the United Kingdom Children’s Cancer Study Group Wilms’ Tumour Study-3 (UKW-3) protocol and to compare CT changes and histopathological classification. Twenty-one nephroblastomas in 15 patients treated on UKW-3 were included. All patients were examined by CT before and after preoperative chemotherapy treatment. CT images were reviewed (estimated volume change and subjectively assessed features). CT changes were compared to histopathological classification. Of the 21 tumours, all five high-risk tumours decreased in volume following chemotherapy (median −79%; range −37 to −91%). The sole low-risk tumour decreased in volume by 98%. Ten intermediate-risk tumours decreased in volume (median −72%; range −6 to −98%) and five intermediate-risk tumours increased (median +110%; range +11 to +164%). None of the five high-risk tumours, compared to 15/16 intermediate or low-risk tumours, became less dense and/or more homogeneous, or virtually disappeared, following chemotherapy. Volume change following chemotherapy did not relate to histopathological risk group. Changes in subjectively assessed qualitative CT features were more strongly related to histopathological risk group.

Intravascular inflammatory myofibroblastic tumors in infancy.

Inflammatory myofibroblastic tumor (IMT), previously described as inflammatory pseudotumor, can occur at any age but is a recognized soft tissue tumor of childhood. Less than 10 previous cases have been described of IMT affecting the heart, in patients ranging from 5 months to 17 years of age. We present three unusual, but similar, cases of IMT in infants, which were all predominantly intravascular in location, one of which was associated with death due to angiodestructive lesions of the coronary and cerebral arteries. These cases demonstrate an apparently distinct phenotype, with a predominant intravascular location of the tumor. Furthermore, this series highlights the difficulty in categorizing such lesions as benign versus malignant on histological grounds alone. IMT should be considered in the differential diagnosis of unusual pediatric intravascular spindle cell lesions.

ISOLATED UNILATERAL TUBEROUS SCLEROSIS-ASSOCIATED RENAL CYSTIC DISEASE IN A NEONATE

We present a male infant with antenatally detected, focal, unilateral apparently isolated renal cystic disease with morphological features of renal involvement in tuberous sclerosis. Only one previous case with similar presentation has been described. Most affected children present with either diffuse bilateral renal cystic disease or extrarenal manifestations. The major genes involved in tuberous sclerosis are now well described, and early onset of severe renal cystic disease in affected children often is related to the presence of a contiguous gene deletion syndrome involving TSC2 and PKD1 on chromosome 16.

Epstein-Barr Virus–Associated Lymphoproliferative Disorder Presenting as Apparently Isolated Gastrointestinal Lesions in Childhood

We present an unusual case of post-transplant lymphoproliferative disorder (PTLD) presenting as apparently isolated gastrointestinal lesions in a pediatric renal transplant recipient. The multiple bowel lesions were related to Epstein-Barr virus and demonstrated the appearance of a monomorphic PTLD that was morphologically indistinguishable from diffuse large B-cell lymphoma. The patient responded to therapy with targeted anti-CD20 immunotherapy. PTLD may manifest as apparently isolated gastrointestinal tract lesions in childhood.

Pathology teach and tell: pediatric gastrointestinal stromal tumor.

A14-year-old boy, with no signi¢cant past medical or family history, presented with a 3-month history of vomiting and epigastric discomfort. There was no dysphagia or hematemesis and no systemic symptoms were present. Review of systems was otherwise unremarkable. On physical exmination, he was a well-nourished adolescent with no stigmata of chronic disease but a ¢rm mass was palpable in the epigastrium. Gastroscopic examination demonstrated macroscopically normal mucosa overlying a smooth polypoid lesion with associated gastric wall distortion by a mass arising from the posterior stomach wall. Computerized tomography con¢rmed the presence of a soft tissue mass within the posterior inferior aspect of the gastric wall, which also appeared to extend into the surrounding transverse mesocolon. Modi¢ed partial gastrectomy was carried out that revealed an umbilicated polypoid nodule arising from the posterior gastric wall, 4 cm in maximum extent, with numerous further nodules present extending into the transverse mesocolon. Several nodules were adherent to transverse colon, a portion of which had been resected (Figure 1). The nodules showed a homogeneous soft, cream-yellow cut-surface throughout. The gastric mucosa was macroscopically unremarkable. Histological sections demonstrated a tumor, apparently originating within the muscularis propria of the stomach, composedpredominantly of interlacing fascicles of plump spindle cells with minimal cellular pleomorphism (Figure 2).The overlyingmucosawas not ulceratedbut showedmoderate nonspeci¢c gastritis.The tumor cells show strong positive immunostaining for CD117 in a membranous pattern (Figure 3) and also were focally positive for CD34.Tumor cells did not express desmin, smooth muscle actin, or S100 protein.