Pediatric and Developmental Pathology

The objective of the study was to examine the causes of stillbirth in the district of Southwest Finland and to assess the importance of postmortem examination and the selection of a suitable classification system for classifying stillbirths. This study is a cohort study where the fetal autopsies were performed in the Department of Pathology at Turku University Hospital, Finland, 2001–2011. Stillbirths from singleton pregnancies at the gestational age of ≥ 24 + 0 weeks (if unknown, gestational weight ≥ 500 g) (n = 98) were selected. In addition, stillbirths from multiple gestations (n = 6) were also analyzed. The causes of stillbirths were classified according to the Relevant Condition at Death classification system. Maternal risk factors and the role of fetal gestational age and weight for the causes of stillbirth were assessed. The most common causes of singleton stillbirth were lethal congenital anomalies, placental insufficiencies, and constricting loops and knots of the umbilical cord. The cause of singleton stillbirth could be determined for 78% of the cases, leaving 22% unclassified. There were no significant differences in the causes of stillbirth by gestational age or weight. Smoking may increase the incidence of placental abruption (P < 0.01). The most common causes of stillbirth in Turku, Finland, are consistent with findings from other high-income countries. With careful postmortem examination and ancillary studies, it is possible to find the cause of stillbirth for most of the cases. Even if the stillbirth is left unexplained, many other harmful conditions can be excluded thus benefiting both the parents and the health care unit.

Neuroblastoma is a common malignant tumor of childhood. Accurate bone marrow (BM) evaluation for metastatic tumor is essential; however, no standardized pathologic workup exists for staging BMs. We examined the diagnostic yield of various BM components and optimal core biopsy (CB) length as part of developing evidence-based recommendations for BM evaluation. After obtaining institutional review board approval, 160 BM biopsies from 50 neuroblastoma patients were retrospectively selected. Hematoxylin and eosin-stained CB and Wright-stained aspirates were scored as positive, negative, or indeterminate. Total/trabecular CB lengths were measured using cellSens software and a DP71 camera (Olympus). Of the 160 BMs, 72 were positive for tumor in any component. Of these, 33 (45.8%) were positive in a single portion of the specimen: 19 CBs and 14 aspirates. Compared with overall diagnosis, sensitivities were as follows: CB 76.3%; aspirate 67.1%; core/aspirate combined 94.7%. Diagnostic CBs had significantly longer trabecular length than nondiagnostic CBs (6.74 mm vs 4.03 mm, P = .006). Positive CBs had longer trabecular space than negative marrows (7.91 mm vs 6.25 mm, P = .002). Nearly 50% of our positive specimens showed diagnostic discordance among the various components examined. However, combining CB and aspirate examination improved sensitivity for tumor detection. We therefore recommend bilateral CBs (>1 cm each) and aspirates for the optimal evaluation of BM for metastatic neuroblastoma.

Decidual vasculopathy (DV) is a general term for a number of lesions involving uteroplacental vessels. It is often seen in preeclamptic placentas and indicates a disorder of uteroplacental malperfusion and is associated with placental ischemia and infarction. Although some have advocated submitting special sections in order to better document DV, it is unclear which placental sections have the highest yield in demonstrating these abnormal vessels. Seventy-six consecutive cases of decidual vasculopathy were identified and evaluated for location of DV, as well as presence of other lesions of ischemic change, infarcts, and retroplacental hematomas. Sections reviewed were the membrane roll (MR), full thickness (FT) sections of the placental disc, and sections specifically of the basal plate (BP). DV was found in the MR in 67.1% of cases, in FT sections in 32.9%, and in the BP in 25.0% of cases (P value = .004). DV was exclusive to the MR in 53.9%, the FT in 14.5%, and the BP in 9.2%. DV was present in 2 locations in 19.7% and in all 3 locations in 2.6%. The presence of DV in any location (MR, FT, and BP) was associated with placental ischemic change but not specifically with infarcts or retroplacental hematomas. The specific location of DV showed no difference in the presence of placental lesions. Our findings indicate DV is often present in 1 location and is associated with lesions of malperfusion. It is recommended that when clinically indicated, additional sections are submitted to demonstrate decidual vasculopathy.

Abnormal muscularization of acinar arteries is the hallmark of persistent pulmonary hypertension of newborn (PPHN), an uncommon disease with high rate of morbidity and mortality. PPHN presents with signs of respiratory distress immediately following birth. We herein report 2 cases presenting as a witnessed sudden unexpected death in the late neonatal period, preceded by respiratory deterioration and in whom the presence of abnormal muscularization of the acinar pulmonary arteries was reminiscent of PPHN. The significance of this report is twofold: to increase the awareness among pediatricians and pathologists of this feature that can present in some cases of Sudden Unexpected Death in Infancy/Sudden Infant Death Syndrome, and to highlight the importance of performing a thorough autopsy in order to identify the abnormality.

Mutations in PIK3CA are associated with overgrowth spectrum disorders including excessive growth in some areas of the body and the central nervous system. Alterations in PIK3CA occur as somatic, postzygotic events and confer a mosaic genotype with variability in phenotypic expression being commonly observed. We describe the second reported prenatal diagnosis of a PIK3CA-related overgrowth spectrum disorder. The prenatal ultrasound features in this case enabled the presumptive, prospective diagnosis to be made which was then confirmed by genetic testing. Subsequent parental testing for mutations in PIK3CA demonstrated normal genotypes. Identification of this mutation prenatally enabled prospective information to be provided to the family and facilitated multidisciplinary perinatal management.

Chronic myelogenous leukemia, BCR-ABL1 positive (CML) is a rare myeloproliferative neoplasm in children and presents even less often as a secondary malignancy in the pediatric population. Below, we report a patient with Philadelphia-negative B-lymphoblastic leukemia/lymphoma, who developed CML several years after achieving complete remission, and summarize the existing literature on the clinical and pathologic features of CML as a secondary pediatric malignancy.

Meckel’s diverticulum is a congenital anomaly present in about 3% of the population and usually asymptomatic. Rarely, a mesodiverticular band extends from the tip of a Meckel’s diverticulum to the mesentery, thought to be due to lack of involution of the left vitelline artery. The presence of this band creates a closed loop through which loops of bowel can become entrapped. Rare case reports have described incarceration of bowel and sudden death in children. We present such a case and discuss this entity.

Bilateral agenesis of the diaphragm is a very rare congenital diaphragmatic defect. Bilateral congenital diaphragmatic hernia (CDH) is much more frequently associated with other anomalies compared with unilateral CDH (70% vs 30%–40%). These include cardiovascular, respiratory (other than lung hypoplasia), gastrointestinal, renal, and genital malformations. We report a case of complete bilateral agenesis of the diaphragm associated with a horseshoe kidney and an imperforate anus. These additional malformations have not previously been reported in association with complete bilateral agenesis of the diaphragm. We also present a review of previous cases of total diaphragm agenesis published in the English language and provide some insights about pathogenesis.

Cystinosis is the most common cause of inherited renal Fanconi syndrome in young children, and typically presents with laboratory findings of a proximal tubulopathy and corneal crystals by one year of age. We describe here renal biopsy findings in a 20-month-old patient with an atypical presentation of distal renal tubular acidosis, diabetes insipidus, and the absence of corneal crystals. Although renal biopsy is usually not necessary to establish the diagnosis of cystinosis, when the patient presents with atypical signs and symptoms, a renal biopsy may be extremely valuable. A 20-month-old boy presented with failure to thrive, polyuria, polydipsia, and rickets. He initially showed evidence of a renal tubular acidosis, mild renal insufficiency, and nephrogenic diabetes insipidus. His initial ophthalmologic examination did not demonstrate corneal crystals. His subsequent workup revealed phosphaturia, suggesting a partial proximal tubulopathy. Concomitantly, a renal biopsy revealed prominent podocytes with an immature glomerular appearance, and electron microscopy analysis showed numerous intracellular crystals within tubular epithelial cells. Subsequent laboratory and genetic testing confirmed a diagnosis of infantile nephropathic cystinosis. This case highlights the variability in the clinical presentation of cystinosis, resulting in an uncommon clinical picture of a rare disease. Given that treatment is available to prolong renal function and minimize the extra-renal manifestations of this disorder, early diagnosis is essential. It is important to raise the index of suspicion of cystinosis by recognizing its subtle morphological changes in young patients, and that nephrogenic diabetes insipidus can be secondary to this disorder.