Pediatric and Developmental Pathology

This review summarizes the general histologic features of acute and chronic hepatitides and highlights those morphologic findings that may suggest or be diagnostic of a specific agent or etiology. The main epidemiologic, clinical, and pathologic features of the hepatotropic viruses are discussed, with an emphasis on pediatric studies and the differential diagnosis of hepatitis in childhood.

The pathogenesis of renal dysplasia is a matter of debate. Recent theories have conceptualized the role of extracellular matrix proteins in the genesis of renal dysplasia. During normal nephrogenesis, collagen type I and III and fibronectins are lost and laminin and syndecan appear once proper induction has occurred. Any deviation from the normal pattern is said to lead to dysplasia. In this study, the expressions of adhesive glycoproteins, laminin, and fibronectin were studied immunohistochemically in 25 autopsy cases of renal dysplasia and normal age-matched control cases. These cases of renal dysplasia were categorized into 3 groups based on the period of gestation: 20 to 26 weeks, 27 to 33 weeks, and 34 to 40 weeks. The immunohistochemical findings were graded from 0 to 4+ based on the visual intensity. Chi-square analysis was used to calculate the difference in expressions of laminin and fibronectin in cases and controls as a whole and within and between age groups. Immunostaining for laminin in all age groups showed a significant difference in expression between dysplastic kidneys (less expression) and normal controls (greater expression). In the case of fibronectin expression, all but 1 group showed a significant difference, with dysplastic kidneys showing more and normal controls showing less expression. The inference derived is that laminin expression decreases and fibronectin expression increases in renal dysplasia compared with normal nephrogenesis.

The confident diagnosis of renal spindle cell tumors in children is often difficult. An immunohistochemical study of WT-1, Bcl-2, and CD34 was performed to determine their expression profiles and to assess the potential utility of these immunohistochemical markers in the differential diagnosis of 36 cases of renal spindle cell tumors of childhood. The cases included 11 stromal predominant Wilms tumors, 12 cellular mesoblastic nephromas, 9 clear cell sarcomas of the kidney (CCSK), and 4 monophasic synovial sarcomas. WT-1 was uniformly positive in primitive undifferentiated stromal Wilms tumors (6 of 6) and negative in the differentiating and differentiated stromal elements of Wilms tumors (0 of 5). WT-1 was also negative in cellular mesoblastic nephromas (0 of 12), CCSKs (0 of 12), and synovial sarcomas (0 of 4). Bcl-2 was expressed in all stromal Wilms tumors (11 of 11), all synovial sarcomas (4 of 4), some CCSKs (4 of 9), and none of the cellular mesoblastic nephromas (0 of 12). Although CD34 was absent in the tumor cells of all the tumors studied (0 of 36), CD34 immunohistochemistry nicely demonstrated the evenly distributed septal capillaries characteristic of CCSK in all 9 cases of this tumor. We conclude that a combination of WT-1 and Bcl-2 immunohistochemistry may aid in the distinction of stromal Wilms tumor, monophasic synovial sarcoma, cellular mesoblastic nephroma, and CCSK.

In recent reports, investigators have described a variant of adult sclerosing rhabdomyosarcoma (RMS) that is characterized by a hyalinizing, matrix-rich stroma. To determine whether this variant occurs in children, we investigated this phenomenon in a recent series of 1207 pediatric patients who had RMS accessioned by the Intergroup Rhabdomyosarcoma Study Group, now part of Children's Oncology Group. Thirteen patients had features of sclerosing RMS; 9 had been diagnosed with alveolar RMS (ARMS), 3 with embryonal RMS (ERMS), and 1 with a spindle cell RMS. Primary sites included head and neck (6 patients), extremities (5 patients), scrotum (1 patient), and retroperitoneum (1 patient). Patients' ages ranged from 0.3 to 16 years. All tumors showed positivity for myogenin, MyoD, and desmin, but only 2 patients demonstrated the strong myogenin staining typically seen in ARMS. Three patients diagnosed with ARMS demonstrated embryonal-appearing foci, and 3 of 4 patients who had nonalveolar tumors had ARMS-like foci. Standard reverse transcriptase–polymerase chain reaction performed on RNA isolated from frozen sections showed 1 ARMS with a positivity for PAX3-FKHR with four patients classified as having ARMS and 1 as having spindle cell RMS were negative for both ARMS fusion transcripts (PAX3- and PAX7-FKHR). Cytogenetic testing in 2 patients who had ARMS-like foci demonstrated mild hyperdiploidy in both patients and a near-tetraploid clone in 1 patient. Sclerosing RMS may arise in children, have mixed ERMS-ARMS histology, originate from the head and neck, and lack strong myogenin staining.

We investigated whether it is possible to accelerate the examination of a pediatric brain at autopsy and thus facilitate its return to the body before a funeral without compromising the quality of the neuropathologic examination. Accelerated fixation and next-day dissection of the brain was performed in selected cases over a 2-year period by using a microwave histologic tissue processor (MicroMed T/T MEGA, Milestone, Sorisole, Italy). Direct comparison of the histologic appearance and immunohistochemical reactivity of 2 cases, 1 fixed by conventional methods and 1 fixed with the accelerated method, was performed in a blinded fashion by a specialist neuropathologist. Examination of rapidly fixed brain by conventional thin coronal sections was readily achieved. There was no appreciable difference between tissue sections stained with hematoxylin and eosin and prepared from conventional formalin-fixed cortical and cerebellar brain tissue and that fixed by rapid heat acceleration. Immunocytochemical studies were not adversely affected by the accelerated heat-fixation process of tissue. Heat-accelerated fixation is a potential method of speeding up the examination of the brain at autopsy without unduly compromising the quality of the neuropathologic examination.

Anencephaly is a designation for congenital absence of the cranial vault with cerebral hemispheres completely missing or decreased to small masses attached to the base of the skull. The etiology is unknown. Whether the bony tissue or soft brain tissue is a primary factor is also unknown. The present study has focused on the posterior cranial fossa in anencephaly. The goal is to determine whether differences in the posterior cranial fossa could provide a basis for subclassification of anencephalic fetal skeletons. Twenty-three human anencephalic fetuses, at gestational ages 13 to 22 weeks, were studied. Radiologic and cephalometric analyses, including measurements of bone sizes and different angles, were performed. Permission for autopsy of the central nervous system was not available. For comparison of anencephalic findings with normal conditions, standards from a recent publication were used. Foot length served as a parameter for age comparison. The study showed 2 morphologic types of the posterior cranial fossa. One type had a fossa cranial morphology close to normal morphology, whereas the other had a malformed and much smaller posterior cranial fossa. The latter condition was presumed to be due to a primary error in chondral and cranial development. The current skeletal subgrouping might be essential for clinicians' or pathologists' future assessment of the autopsy results. The skeletal subgrouping should, if possible, be associated with karyotyping and analysis of the central nervous system. The goal is to distinguish between congenital conditions resulting in anencephaly and acquired conditions resulting in anencephaly.

Langerin is a recently identified lectin for which antibodies can be used as immunohistochemical markers of Langerhans cells (LCs). We describe the distribution of staining in autopsy pediatric tissues, dermatopathic and other reactive lymph nodes, and childhood histiocytic lesions using the 12D6 antibody (Novocastra). We also correlate CD1a (antibody O1O) staining to these factors. Langerin on epidermal LCs has a coarsely granular cell membrane and a cytoplasmic staining pattern that is always associated with CD1a expression. All 6 skin samples had Langerin⁺/CD1a⁺ LCs within the epidermis. Six of 8 thymuses showed single scattered dendritic-shaped cells in the medulla and rare cells within Hassall corpuscles that coexpressed Langerin and CD1a. Cortical thymocytes were CD1a⁺/Langerin^-. Four of 8 livers examined showed a sinusoidal lining pattern of Langerin+/CD1a^-. All 15 autopsy lymph nodes showed a similarly strong Langerin⁺/CD1a^- sinus pattern of staining on fixed tissue elements, mostly in medullary sinuses. All 12 dermatopathic lymph nodes showed accumulation of Langerin⁺/CD1a⁺ cells in the pale paracortical nodules. All 24 instances of LC histiocytosis (LCH) were Langerin⁺/CD1a⁺. All 12 non-LCH histiocytic disorders are negative for Langerin in the histiocytes of interest. We conclude that Langerin is coexpressed with CD1a on LCs and LCH. Lymph node sinuses and hepatic sinusoids show Langerin⁺/CD1a^-cells, indicating that, when used alone to confirm LCH infiltration, the 12D6 antibody should be used with caution. At other sites, its diagnostic accuracy is similar to that of CD1a.

Systemic form of juvenile xanthogranuloma with involvement of liver and bone marrow is reported in a 2-month-old female infant who presented with hepatosplenomegaly, severe anemia, and thrombocytopenia. There was no skin lesion, nor bone lesion. The enlarged liver has generalized yellowish spots. The diagnosis of juvenile xanthogranuloma was made by pathologic findings of marrow and portal tract infiltration by S-100 negative, CD1a negative, CD68 positive, and Factor XIIIa positive large pale to foamy histiocytes with Touton giant cells, and lack of Langerhans cell granule by electron microscopic examination. The patient was treated with Vinblastine and Etoposide, and experienced slow and gradual disease regression in one year. To the best of knowledge, this is the first documented case of bone marrow involvement in systemic juvenile xanthogranuloma.

We present the case of a 28-h-old female infant born at 37 weeks of gestation with a rare congenital malformation consisting of a pentad of findings: ectopia cordis, a midline supraumbilical wall defect, a defect of the lower sternum, absent pericardium, and an anterior diaphragmatic defect. This constellation of defects is known as the pentalogy of Cantrell. Additional autopsy findings included a bilateral cleft lip and palate, bilateral pulmonary hypoplasia, an atrial septal defect, and a patent ductus arteriosus. We present this case because of its rarity and discuss the pathologic findings.

We report a case of a benign solitary fibrous tumor that occurred in the right shoulder of a 9-year-old girl. This case is remarkable due to the unusual location of its occurrence and the young age of the patient. In addition, cytogenetic analysis revealed a karyotype unreported in this neoplasm: 46,XX,der(4)t(4;9)(q31.1;q34), del(9)(p22p24),der(9)t(4;9)(q31.1;q34)ins(9;?)(q34;?) (17 cells)/46,XX (3 cells).

Congenital pulmonary airway malformation, or congenital cystic adenomatoid malformation, is postulated to be a disorder of pulmonary airway morphogenesis and encompasses 5 different types with distinct levels or stages of tracheobronchial development. We present a unique case of type 2 congenital pulmonary airway malformation with a previously undocumented combination of multiple extrapulmonary anomalies, featuring ipsilateral multicystic renal dysgenesis, contralateral renal agenesis, and ovarian germ cell hypoplasia, diagnosed in a 19-week gestational age fetus by autopsy. Epithelial cells comprising the pulmonary lesions were positive for thyroid transcription factor-1, surfactant protein-B, and cytokeratin-7 but negative for cytokeratin-20 immunostainings, with the pattern seen in normal terminal bronchioles. Chromosomal analysis showed a normal female karyotype, despite a high estimated risk for Down syndrome suggested by the low maternal serum α-fetoprotein level.