Abstract Approximately 20% of all twin pregnancies are monochorionic. Between 9% and 15% of all monochorionic twin gestations are complicated by severe chronic twin-to-twin transfusion syndrome (TTTS), characterized by a gradual shift of blood volume from the donor twin to the recipient twin through placental vascular connections 1-3. The prognosis of severe, untreated chronic TTTS diagnosed in mid-trimester fetuses is extremely poor, with mortality rates exceeding 70% 4. Following publication of the Eurofoetus trial results in 2004, laser photocoagulation of the intertwin anastomoses has become accepted as the optimal first-line therapy for severe TTTS diagnosed before 26 weeks of gestation. While laser treatment of vascular communications was initially limited to selected fetal treatment centers, its increasingly widespread use has resulted in exposure of more pathologists, even in less specialized institutions, to laser-treated placentas. Furthermore, the surge in laser coagulation has revived the general medical, scientific and public interest in the placental and choriovascular findings in monochorionic twin placentas. The pathologist's understanding of the pathophysiology of TTTS and of the TTTS-associated placental pathology, including the findings related to laser ablation of the anastomoses, can be of great benefit to the involved obstetrical/neonatal/surgical team and, ultimately, to the patients. In this review, we summarize the current knowledge of the placental contributions to TTTS and other complications of monochorionic twinning, and describe the strengths and limitations of placental examination in these settings. This overview may serve as a template to generate consensus guidelines for standardized and evidence-based pathologic evaluation of monochorionic twin placentas.

Abstract

Objectives:

(1): To determine if there is an increased prevalence of vitamin D deficiency (VDD) in cases of sudden death in infancy and childhood; (2): to establish if there is a link between VDD and infection; and (3): to assess if the level of Vitamin D can be related to abnormalities in the skeletal survey and rib histology in our cohort. Material and methods: The post mortem reports of cases in which vitamin D levels were measured in 2009 and 2010 were retrieved. In those cases where parental consent for audit had been granted, rib histology and the skeletal survey were reviewed.

Results:

Plasma 25-hydroxyvitamin D levels were measured in 41 post mortem cases. 10/41 cases (24.5%) had adequate levels, 5/41 (12%) had sub-optimal levels, 16/41 (39%) had moderate deficiency and 10/41 (24.5%) had severe deficiency. We had only 4 cases with VDD and infection. There were 25 cases of unexplained death in our cohort, 76% of these had inadequate vitamin D levels. The rib histology was abnormal in 69% of cases that had inadequate vitamin D levels, while the radiology was abnormal in 19% of cases.

Conclusions:

A significant proportion of infants and children who died suddenly and unexpectedly had inadequate levels of vitamin D. We were unable to confirm or exclude an association between VDD and infection.Further multi-centre studies are needed to confirm our findings and explore possible associations between VDD and other known risk factors for sudden infant death syndrome (SIDS).

Abstract

Background:

Eosinophilic/T-cell chorionic vasculitis (ETCV) is characterized by mixed T-cell, eosinophilic, and histiocytic infiltrates within the chorionic vessel wall. We sought to better characterize this lesion both with respect to other pathological correlates and the T-cell populations involved.

Methods:

Epidemiological data and other pathologic diagnoses, including concurrent chronic villitis (CV), were tabulated for each case of ETCV diagnosed at our institution over a 6 year period. CD3, CD25, FOXP3, and dual FOXP3-CD3 immunostains were used to identify regulatory T-cell populations in ETCV and CV. Cells positive for CD3, FOXP3, and CD25 were quantitated by manual counts of 40x fields at the sites of ETCV and CV and FOXP3:CD3 and CD25:CD3 ratios were calculated. Digital analysis of ETCV and CV using the dual FOXP3-CD3 immunostain was also performed on select cases.

Results:

Of 31 ETCV cases, 10 (32%) were accompanied by chronic villitis and 13 (42%) by a thrombus in the vessel affected by ETCV. The mean Treg cell marker:CD3 ratios in ETCV ranged from 0.18 to 0.26 by manual count and digital analysis but the counts did not statistically differ by method. The mean Treg cell marker:CD3 ratios in CV ranged from 0.37 to 0.39 by manual count and 0.19 by digital analysis, but these counts also did not statistically differ by method.

Conclusions:

Chronic villitis was seen in a third of ETCV cases. FOXP3-positive and CD25-positive regulatory T-cells represent a significant subpopulation of T cells in ETCV and CV, suggesting that they may play a role in these entities.

ABSTRACT

The Accreditation Council for Graduate Medical Education (ACGME) has provided guidance for specialty and subspecialty fellowship training programs by defining 6 core competencies that must be met. Furthermore, the ACGME has defined several program requirements for pathology training, including those applicable to several pathology subspecialties. However, the requirements are broad and lack specific details, particularly as they pertain to the unique nature of pediatric pathology. The Fellowship Committee of the Society for Pediatric Pathology examined the ACGME requirements and interpreted the guidelines with respect to their application to training in pediatric pathology. The Committee worked within the ACGME guidelines to provide an expanded and more comprehensive set of guidelines for use by pediatric pathology fellowship directors and trainees. The resultant document lists the educational goals, core competencies, and program requirements with specific application to pediatric pathology. In addition, methods for assessing and documenting the progress of the individual trainees as they progress through each requirement are provided. It is to be emphasized that many of the guidelines set forthwith are flexible, and allowances should be made for individual differences of each training program.

ABSTRACT

Similar to nephrogenic adenomas in adults, those in children are rare benign lesions that often occur in the setting of previous surgery or chronic irritation of the urinary tract. These lesions often present with hematuria and/or as polypoid or papillary lesions on cystoscopy, which may indicate malignancy. We sought to evaluate the various patterns of nephrogenic adenoma occurring in the pediatric population and better characterize the immunophenotype of these lesions. We reviewed 21 cases of nephrogenic adenomas from urinary bladder biopsies of 16 patients. Most patients had a history of urinary bladder augmentation with recurrent urinary stones and urinary tract infections. Many cases presented as a papillary or polypoid mass on cystoscopy. The most common morphologic patterns are papillary, tubulocystic, and a mixed pattern of papillary and tubulocystic, followed by cystic and tubular. On immunostaining, PAX-2, PAX-8, CK7, and MUC-1 provided the most diffuse and intense positive reactivity for nephrogenic adenoma, whereas CD10 and P504S were focal and lesser in intensity when positive. p63 and PAX-5 were consistently negative. We conclude that, although rare in children, nephrogenic adenoma should be included in the differential diagnosis of papillary/polypoid lesions in the urinary tract, especially in the context of previous surgery, chronic irritation from recurrent urinary tract infections, or stones. The immunohistochemistry profile of nephrogenic adenomas in our study also provides evidence that these are derived from distal renal tubular cells. In difficult cases, an immunohistochemical panel consisting of cytokeratin 7, PAX-2, PAX-8, and MUC-1 may be useful.

Abstract

Background:

a proportion of antepartum/intrapartum stillbirths (IUD), with normal or elevated body weight (BW) centile also show an elevated brain/liver weight ratio. We postulate that this may be an indication of intrauterine malnourishment/incipient intrauterine growth restriction (IUGR), which may have a bearing on the cause of death.

Design:

searching our departmental database, we identified 331 IUD/intrapartum deaths (254; 77%) or early neonatal deaths (77; 23%), {greater than or equal to}37/40 weeks gestation in a four year period. The customised BW centile, brain/liver weight ratio (BLR), brain/thymus weight ratio (BTR) fetus/placenta weight ratio (FPR) and maternal BMI were calculated. BLR of >4.0 and BTR of >60 was regarded as abnormal.

Results:

Of the 331 cases, the BLR was >4.0 in 71 (21.4%). 19 (26.7%) of the 71 had a BW above the 25th centile and these were all IUD's. 8 deaths were explained. In the 11 unexplained deaths, the BTR was raised in 5 and FPR was elevated in 7. 3 of these 11 mothers had impaired glucose tolerance and 7 were overweight or obese.

Conclusion:

In the absence of a definitive cause, a raised BLR in an IUD with a normal body weight centile, is likely to indicate nutritional impairment/incipient IUGR. The majority of these deaths are associated with maternal obesity, with or without impaired glucose tolerance. Recognition of features of IUGR in IUDs of normal birth weight may help to understand the death. In these cases, placental growth may be insufficient to support a macrosomic fetus, leading to late nutritional impairment and death.

Abstract

Background:

Beckwith-Wiedemann Syndrome (BWS) is an imprinting disorder characterized by overgrowth, congenital malformation and tumor predisposition. Children with BWS have a higher incidence of tumors, commonly intra-abdominal tumors such as Wilms tumor, hepatoblastoma and adrenal cortical carcinoma. Here, we describe the first case of a rare hepatic malignancy of nested stromal epithelial tumor (NSET) of the liver in a child with BWS. Case Report: A 22-month old girl with BWS had a new incidental liver mass. Her alpha-feto protein levels were normal. She underwent a liver segmentectomy.

Results:

Histopathological features combined with immunohistochemistry results (positivity for pan keratin (AE1/3), CD56, CK19, CD117 and CD99 (weak membranous pattern), β-catenin and WT1-COOH (focal)), were diagnostic of NSET of the liver.

Conclusions:

This is the first case of NSET of the liver associated with BWS. Its occurrence at such an early age is consistent with the tumor predisposition of BWS.

Abstract Giant cell tumor of bone is a neoplasm rarely seen in children. Goltz syndrome is a disorder that affects multiple ectodermal and mesodermal tissues and has occasionally been associated with giant cell tumors of bone. Our case of giant cell tumor in a five-year-old girl with Goltz syndrome suggests that this syndrome provides a unique situation, wherein the practitioner should consider giant cell tumor of bone even in a pediatric setting.

Abstract Glypican-3 (GPC3) is a proteoglycan thought to play an important role during development. Germline GPC3 mutations are seen in the rare Simpson-Golabi-Behmel syndrome (SGBS), which predisposes patients to Wilms tumor, hepatoblastoma, and neuroblastoma. While numerous adult tumors have been evaluated by immunohistochemistry (IHC) for GPC3, no comprehensive assessment has been done in pediatric tumors. We investigated GPC3 expression in 143 pediatric central nervous system (CNS) tumors and 271 non-CNS tumors. Among non-CNS tumors, GPC3 expression was seen in 9/9 (100%) hepatoblastomas, 4/6 (67%) malignant rhabdoid tumors, 5/13 (38%) Wilms tumors, 11/37 (30%) alveolar rhabdomyosarcomas, and 8/45 (18%) embryonal rhabdomyosarcomas. All 136 neuroblastomas, 14 Ewing sarcoma/primitive neuroectodermal tumors and 11 synovial sarcomas were immunonegative for GPC3. Among CNS tumors, GPC3 had restricted expression with positivity in 6/6 (100%) AT/RTs and 1/4 (25%) craniopharyngiomas. The remaining 136 CNS tumors, including 23 medulloblastomas, 21 pilocytic astrocytomas, 13 gangliogliomas, 12 ependymomas, 12 glioblastomas, 11 choroid plexus neoplasms, 10 diffuse astrocytomas (grade II/III), 10 meningiomas, 8 dysembryoplastic neuroepithelial tumors, 8 oligodendrogliomas, 3 craniopharyngiomas, 3 germinomas, and 2 neurocytomas, were entirely negative for GPC3. These results showed GPC3 positivity in a number of non-CNS tumors with no consistent discrimination between tumors that are or are not associated with SGBS. Within the CNS, GPC3 positivity was limited to a small subset of CNS neoplasms and may serve as a useful positive diagnostic biomarker (P value <0.0001) in addition to negative INI1/BAF47/SMARCB1 staining to differentiate AT/RT from other high-grade pediatric brain tumors.

Abstract Not applicable.