L. David Mirkin

Hepatic failure in infants on total parenteral nutrition (TPN): Clinical and histopathologic observations*

Total parenteral nutrition (TPN) is an important adjunct in the care of neonates with surgical disorders. Although cholestasis complicates TPN in 30% of cases, it is usually transient in nature. This report, however, describes 9 instances (8 fatal) of progressive liver failure in surgical neonates who were maintained on prolonged TPN (6 wk-15 mo) and demonstrated distinct hepatic pathologic changes. Diagnosis included complicated gastroschisis, (2) bowel atresia with peritonitis (1), NEC (4), prune belly and antenatal peritonitis (1), and total colonic and ileal aganglionosis (1). Mean gestational age was 35 wk with sexes equally affected. The 8 fatal cases had persistant cholestasis that failed to respond to changes in parenteral protein or glucose concentrations. Enteral feedings were not tolerated. Clinical deterioration was manifested by increasing serum bilirubin (22–35 mg%), clotting dysfunction, enzyme elevations (SGOT), and hepatomegaly. Histologic examination of the liver showed significant distortion of hepatic architecture with hepatocytes arranged in pseudoacini rather than cords and trapped by fibrous tissue. Bile duct proliferation was noted, but ducts contained no bile. Bile plugs were seen in canaliculi only. Hepatocytes showed diffuse vacuolization (+for fat) and contained brown pigment (+for iron). Portal triads were free of inflammation. Ultrastructural examination showed hepatocytes in an acinar array surrounded by collagen. Cystic changes in the endoplasmic reticulum, osmophilic cytoplasmic pigment, lipid droplets, and severe glycogen depletion consisten with acytotoxic insult were seen. Prematurity, immature liver function, and amino acid imbalance with formation of a toxic bile salt are implicated in these findings. Peritonitis, sepsis and inability to tolerate enteral feedings may also play a role. These observations indicate a need to modify TPN application in selected prematures requiring long-term nutritional support.

Mucoepidermoid carcinoma of the bronchus in a 4-year-old child. A high-grade variant with lymph node metastasis

A high‐grade mucoepidermoid carcinoma with lymph node metastasis occurred in the bronchus of a 4‐year‐old child. The tumor was pedunculated, obstructive, and invasive. Squamous and glandular elements were seen on light and electron microscopic examination. This is a very rare tumor in the pediatric age group. This is the first instance of this lesion associated with metastasis.

The leptomeningeal vein. A site of re‐entry of leukemic cells into the systemic circulation

The possible routes of transvascular migration of leukemic cells were studied in guinea pigs with an L2C lymphoblastic cell‐line inoculation leukemia. The leukemic infiltrates were found mostly in and around the superficial leptomeningeal veins, paralleling findings in human leukemia. Reconstructions, based on thin serial sections (Epon blocks), allowed us to conclude: (1) leukemic cells do proliferate under the vascular endothelium; (2) the endothelium when pushed away from its basement membrane degenerates and ultimately disintegrates; (3) junctions between adjacent endothelial cells tend to be preserved, even when the rest of the endothelial cytoplasm has disintegrated; (4) leukemic cells will eventually re‐enter the circulation; (5) leukemic cells, either singly or in groups, cross through endothelial pores in otherwise intact endothelial cells, rather than through opened‐up junctions. It is concluded that leukemic cells cross the endothelium either through endothelial pores, which they in some way engender, or through large gaps left by disintegrating endothelium, the latter possibly intravasation.

Acute Disseminated Aspergillosis During the Neonatal Period: Report of an Instance in a 14-day-old Infant

We describe an infant who died with extensive lesions of disseminated aspergillosis on the 18th day of postnatal life. Aspergillus fumigatus was re covered from blood cultures. Initial clinical manifestations were suggestive of hepatitis, and steroids and antibiotics were used in the treatment. This therapy may have fostered the onset of an opportunistic mycosis. Advanced multi- systemic aspergillotic lesions were seen at autopsy, especially prominent in lungs and gastrointestinal tract. The extent and magnitude of the lesions observed suggest inception of the disease very early in life, although no case of human aspergillosis has been known to be congenital. Neonatal aspergillosis is poorly characterized. Only four previously reported cases came to our notice in which the disease could be diagnosed in the first month of life. The ubiquitous nature of pathogenic Aspergillus, joined to aggressive treatments designed to achieve increased survivals in neonatology, could potentially result in greater numbers of cases of this and other uncommon mycoses.

Angiomatoid Malignant Fibrous Histiocytoma with Extensive Lymphadenopathy Simulating Castleman's Disease

We report the association in a 10-year-old boy of an angiomatoid malignant fibrous histiocytoma (AMFH) of the left thigh with ipsilateral inguinal, pelvic and extensive retroperitoneal lymphadenopathy, and severe systemic manifestations. These include growth retardation, fever, severe anemia, hypergammaglobinemia, and hypoalbuminemia. At ultrastructural level the tumor was characterized by an abundance of myofibroblasts, occasional histiocytes, and small vessels with marked reduplication of the basal lamina. Biopsies of the inguinal and abdominal lymph nodes showed follicular hyperplasia and massive plasmacytosis indistinguishable from Castlemans disease (giant lymph node hyperplasia) of plasma cell type. The radical surgical excision of the primary tumor in the thigh resulted in the disappearance of the abdominal lymphadenopathy and a marked reduction in size of the pelvic lymph nodes with marked decrease of the gammaglobulins, thus proving that the nodal lesions were the expression of a reactive process to the tumor rather than a coincidental independent lymphoproliferative disorder. Retroperitoneal and pelvic node dissection was performed 1 year after the radical excision of the thigh tumor because of persistent pelvic lymphadenopathy and failure of serum immunoglobulins M and A to return to normal level, with a recent peak of IgA to twofolds that of normal value. Metastatic AMFH was found in the three pelvic nodes. One month postoperatively IgA returned to near normal level whereas IgM remained slightly elevated.

Massive congenital mesenchymal malformation of the lung: a case report with ultrastructural study.

An unusual congenital tumorous malformation of mesenchymal tissue caused severe respiratory distress in a premature infant. The solid mass, which replaced almost the entire left lung, was composed of interlacing fascicles of spindle cells that percolated through otherwise well-developed fetal lung tissue. The normal anatomic arrangement of bronchial components was altered, but bronchial cartilages were present. Ultrastructural study of the lesion showed mesenchymal cells with fibroblastic differentation.

Transvascular migration of L2C leukemic cells studied in the liver of the guinea pig

The possible routes of transvascular migration of leukemic cells in the liver were studied in guinea pigs with an L2C lymphoblastic cell-line inoculation leukemia. Invasion of the hepatic parenchyma theoretically can occur in three ways: 1. Through the intact sinusoidal endothelium, utilizing either pre-existent gaps (normal in the liver), or newly created pores, whether interendothelial or intraendothelial. We could not convincingly demonstrate this, but could not wholly exclude this either. 2. After destruction or retraction of the endothelium, either on account of the remarkable sinusoidal engorgement and distension by masses of leukemic cells, or by direct assault on the endothelium by the leukemic cells. We can clearly demonstrate the former, and hold it to be the major cause of hepatic infiltration. Evidence for a direct endotheliolytic effect was not uncovered in our studies. 3. Secondary infiltration from the portal triads. Heavy leukemic infiltration of the triads, whether from the portal or hepatic veins, or from the lymphatics, is indeed and early an consistent feature - but the infiltration of the hepatic lobule shows no peripheral, or any other zonal preference. Through the intact sinusoidal endothelium, utilizing either pre-existent gaps (normal in the liver), or newly created pores, whether interendothelial or intraendothelial. We could not convincingly demonstrate this, but could not wholly exclude this either. After destruction or retraction of the endothelium, either on account of the remarkable sinusoidal engorgement and distension by masses of leukemic cells, or by direct assault on the endothelium by the leukemic cells. We can clearly demonstrate the former, and hold it to be the major cause of hepatic infiltration. Evidence for a direct endotheliolytic effect was not uncovered in our studies. Secondary infiltration from the portal triads. Heavy leukemic infiltration of the triads, whether from the portal or hepatic veins, or from the lymphatics, is indeed and early an consistent feature - but the infiltration of the hepatic lobule shows no peripheral, or any other zonal preference. In both portal and hepatic veins, leukemic cells transverse the endothelium through a cytoplasmic “pore”, adjacent to cell junctions, without obvious damage to the endothelium.

Hyaline Membranes in Postmature Infants

Hyaline membranes in 21 of postmature infant autopsies were studied, using 27 term infant autopsies as the control population. The occurrence of hyaline membranes was much higher in postterm (86%) than term infant autopsies (26%). Seventeen of 21 postmature infants had clinical and microscopic evidence of aspiration, contaminated by meconium in 14, suggesting that meconium and/or amniotic aspiration may be an etiologic factor in postmature hyaline membrane formation. Thirteen infants had severe hyaline membrane formation, microscopically distinguishable from hyaline membrane disease of the premature only by the maturity of the underlying lung. Besides the pulmonary findings, little difference in organ histology was observed between the two groups. This study showed that hyaline membrane formation resulted in asphyxia and respiratory failure in the majority of the postmature infants who were already troubled with hypoxia and a combined respiratory and metabolic acidosis secondary to meconium aspiration, and eventually led to death.Hyaline membranes in 21 of postmature infant autopsies were studied, using 27 term infant autopsies as the control population. The occurrence of hyaline membranes was much higher in postterm (86%) than term infant autopsies (26%). Seventeen of 21 postmature infants had clinical and microscopic evidence of aspiration, contaminated by meconium in 14, suggesting that meconium and/or amniotic aspiration may be an etiologic factor in postmature hyaline membrane formation. Thirteen infants had severe hyaline membrane formation, microscopically distinguishable from hyaline membrane disease of the premature only by the maturity of the underlying lung. Besides the pulmonary findings, little difference in organ histology was observed between the two groups. This study showed that hyaline membrane formation resulted in asphyxia and respiratory failure in the majority of the postmature infants who were already troubled with hypoxia and a combined respiratory and metabolic acidosis secondary to meconium aspiration, and eventually led to death.

Immunohistochemical demonstration of altered functional differentiation of pancreatic tissue in sacrococcygeal teratomas

The finding of teratomas with mature-appearing pancreatic tissue showing abnormal production of immunoreactive amylase appears to contradict earlier suggestions that somatic tissue in teratomas that appears mature also functions normally. It therefore seems judicious to study carefully both morphologic and functional characteristics of tissues in teratomas before utilizing them as experimental models of tissue differentiation, since at least in the case of human amylase, functional differentiation does not always follow morphologic differentiation.

Spinal Malignant Schwannoma in a 5-Year-Old Boy: Ultrastructural Evidence of Its Perineurial Origin

A case of a malignant spinal schwannoma in a 5-year-old boy is reported. Electron microscopic findings permitting the classification of the tumor and its possible origin from the nerve sheath (perineurial cell) are discussed.