Maternal malignant melanoma with placental metastasis: a case report with literature review

Histologic detection of micrometastatic melanoma in the placenta led to the clinical diagnosis in the mother. Metastases were present in the intervillous space and in villous stroma. The infant has survived and has no evidence of disease at one year of age. The mother died of metastatic disease 6 months post-partum. Literature review shows that only 25% of infants with placental metastatic melanoma succumb to the disease. In a review series of 16 cases, there are some maternal clinical factors which seem to have some bearing on the likelihood of fetal metastasis and death from disease. Features that are associated with an unfavorable fetal/infant prognosis are: maternal age less than 30 years, primiparity, leg primary site, disease onset greater than 3 years prior to pregnancy, node-1 metastatic status prior to pregnancy, M4 status in third trimester, birth at greater than 36 weeks' gestation, male sex. Extent of penetration of metastases into the villi does not have prognostic significance.     

Simultaneous choriocarcinoma in mother and newborn infant

A male infant, born following an uncomplicated pregnancy, was severely anaemic at birth following significant foeto-maternal haemorrhage. At three weeks of age a tumour was found in the liver with evidence of metastatic disease in the lungs. The infant died before treatment could be started. Postmortem revealed choriocarcinoma which led to subsequent diagnosis in the mother who also had pulmonary metastases. The mother has been successfully treated. The case is described in detail and followed by a discussion and a literature review of reported cases of simultaneous choriocarcinoma in infant and mother. © 1995 Wiley-Liss, Inc.     

Congenital renal rhabdoid tumor with placental metastases: immunohistochemistry, cytogenetic, and ultrastructural findings.

Malignant congenital tumors of fetal origin are rare lesions, the most common type being congenital neuroblastoma. Although prenatal diagnosis is possible in large tumors, occasionally the tumor will be diagnosed first by its metastatic involvement of the placenta. Placental metastases can reflect either maternal or fetal primary sites, and each has relatively specific patterns of placental involvement. We describe the clinical and pathologic features of a widely metastatic congenital renal rhabdoid tumor with its placental and autopsy findings, and include the immunohistochemical, cytogenetic, and ultrastructural features. The pathologic features of the placenta in congenital renal rhabdoid tumor with placental metastasis have not been previously described. The examination of the placenta in this case led to the initial diagnosis and obviated the need for additional diagnostic procedures.     

Female pseudohermaphroditism with phallic urethra in the offspring of a mother with an adrenal tumor

BACKGROUND: Female pseudohermaphroditism is a disorder in which 46,XX females with ovaries do not develop as normal women. This disorder is caused by overexposure of a female fetus to androgens during intrauterine life. We describe a masculinized female infant who was born to a mother who had virilizing signs. PATIENT REPORT: The patient had a normally formed phallus and a completely fused scrotum. Baseline as well as stimulated adrenal hormones and testosterone values were in the normal range in the infant. No androgens were given to the mother during pregnancy. Serum 17-OHP, DHEA-S, and testosterone levels were all elevated in the mother. Imaging studies revealed a tumor mass over the left kidney pole. Histologically it was an adrenal tumor. CONCLUSIONS: Although a maternal adrenal tumor is a rare cause of female pseudohermaphroditism, the physician must bear this in mind when confronted with a newborn or infant with 46,XX karyotype and cryptorchidism with a phallic urethra.     

High-grade osteosarcoma of the extremity: differences between localized and metastatic tumors at presentation

BACKGROUND: In osteosarcoma, as in other tumors, the presence of metastases at presentation is generally considered a consequence of late diagnosis. To verify this, the authors investigated whether there was a relationship between the stage of the disease at presentation and several clinical and pathologic characteristics, including the interval between the onset of first symptoms or signs and the final diagnosis. PATIENTS AND METHODS: One thousand seventy-one patients with high-grade osteosarcoma of the extremity were observed between 1980 and 1999. Of these, 891 had a localized tumor and 180 had metastases at the time of diagnosis. RESULTS: Compared with patients with localized disease, patients with detectable metastases at the time of diagnosis had higher serum levels of alkaline phosphatase, larger primary lesions, and tumors often located in the femur and humerus. In terms of time to diagnosis, the interval between the onset of first symptoms and the final diagnosis was significantly shorter in patients with metastases than in patients with localized tumor. This surprising finding probably reflects a more rapid growth of the tumor. CONCLUSIONS: These results suggest a different biologic phenotype and aggressiveness of the tumor in a subgroup of patients and that the stage of the disease at presentation depends more on the properties of these tumors than on late diagnosis.     

MATERNAL PULMONARY ADENOCARCINOMA METASTATIC TO THE FETUS: FIRST RECORDED CASE REPORT AND LITERATURE REVIEW

We report the first maternal pulmonary adenocarcinoma metastatic to the fetus, as well as an updated literature review. Review of the literature revealed that there have been only 67 cases of maternal malignancy metastatic to the products of conception. These were mostly malignant melanoma and hematopoietic tumors. A 46-year-old multiparous woman with metastatic pulmonary adenocarcinoma, diagnosed at 23 weeks gestation, delivered a male infant who appeared normal at birth. The mother died 2 days after delivery. The child developed multiple scalp tumors at 2 weeks of age. The tumors recurred rapidly after initial resection. Wide local excision of the involved scalp and skin graft coverage was performed at 14 weeks of age. Histopathology of these tumors was identical to that of the maternal tumor. The maternal origin of these tumors was confirmed by fluorescence in situ hybridization (FISH). The child is now 5 years old and free of disease.     

Angiotensin converting enzyme activity in infancy is related to birth weight

AIMS: (a) To measure infant angiotensin converting enzyme (ACE) activity in healthy term infants at birth and during the first three months of life. (b) To determine the relation between serum ACE activity and infant feeding practice during this period. (c) To investigate the relation between serum ACE activity and birth weight and other potential contributing factors including acid-base status at birth, gestation, and maternal ACE genotype. METHODS: Prospective study of term infants, with clinical and feeding data collected from parents and medical records, and serum ACE measured in the infant at birth and 1 and 3 months of age, and in the mother at the time of birth and one to three months after birth. RESULTS: At birth and 1 and 3 months of age, infant serum ACE activity was twice that of maternal ACE activity. Infant ACE activity at birth and 1 and 3 months did not significantly differ between breast and formula fed infants. There was a highly significant negative correlation between infant ACE activity at 3 months and birth weight (r = -0.52; p < 0.001). This persisted after the conversion of birth weights to z scores (r = -0.34; p = 0.03). ACE activity at 3 months was also related to placental weight (r = -0.30; p = 0.02) and maternal age (r = -0.30; p = 0.05). The strong correlation between serum ACE activity and birth weight z score persisted after adjustment for maternal age and placental weight (r = -0.34; p = 0.03). CONCLUSION: As ACE is increasingly identified as a risk factor for cardiovascular disease, serum ACE activity in infancy may contribute to the link between low birth weight and later cardiovascular events.     

Inflammatory bowel disease in mother or father and neonatal outcome

Even a minor decrease in birthweight predisposes to adult disease. Inflammatory bowel disease (IBD) in the mother is a risk factor for low birthweight and preterm infants. This study investigated the effect of IBD in the mother or father, adjusting for confounders, on the newborn infant, with the focus on birthweight and pregnancy duration. A total of 10399 single-birth mother-infant pairs was prospectively enrolled within the ABIS project (All Babies In Southeast Sweden). Outcome measures included birth week, preterm birth (<37 wk), birthweight, low birthweight (<2500 g), birth length, caesarean section and neonatal hospital care. Ulcerative colitis (UC) in the mother was associated with lower birthweight in the infant (adjusted difference: -330 g, adjusted 95% confidence interval: -509 to -150 g, p < 0.001), and with even lower birthweight when the mother was treated with Mesalazine or steroids. No decrease in birthweight was seen in infants whose mother suffered from Crohn's disease (CD) (adjusted difference: -65 g, adjusted 95% confidence interval: -354 to 224 g, p > 0.05). Maternal UC or CD did not affect the pregnancy duration. The neonatal outcome of infants whose father suffered from UC and CD did not differ from the control group. CONCLUSION: UC in the mother affects the birthweight of the infant, which may predispose to future disease in the infant. Most women and men with UC and CD can, however, expect a healthy child with neither preterm birth nor low birthweight.     

The role of bone marrow evaluation in the staging of patients with otherwise localized, low-risk neuroblastoma

BACKGROUND: Bone marrow aspirations and biopsies are standard staging procedures for neuroblastoma because the tumor frequently metastasizes to the bone marrow. The presence of bone marrow metastases indicates stage 4 or 4S neuroblastoma by International Neuroblastoma Staging System (INSS) criteria; these stages are also associated with other metastatic sites of disease. We questioned whether bone marrow studies changed the staging or treatment of children with localized, completely resected tumors if there was no other evidence of metastatic spread. If stage of disease rarely changed with bone marrow results, it might be possible to avoid this procedure in a subset of patients with neuroblastoma. PROCEDURE: The staging studies of patients with INSS stage 1 (n = 29), 4 (n = 60), and 4S (n = 13) neuroblastoma from two institutions were reviewed. RESULTS: There were no patients upstaged from stage 1 to 4 or 4S by bone marrow metastases alone. Fifty-nine of 60 stage 4 patients had other sites of metastases on imaging studies, the remaining patient had an unresectable primary tumor and marrow disease. All subjects with stage 4S disease had liver metastases. CONCLUSIONS: Bone marrow studies did not contribute data that changed the stage of patients who had surgically resectable tumors and no evidence of metastatic spread on imaging studies. When present, metastatic spread to the marrow was associated with advanced local tumors or other sites of metastatic disease. Given the relatively small size of our study population, further studies are warranted that investigate the utility of bone marrow studies for patients who otherwise have INSS stage 1 neuroblastoma.     

Neonatal Choriocarcinoma of Liver

Neonatal choriocarcinoma associated with a seemingly normal gestation is rare. A total of 20 cases of either primary or metastatic choriocarcinoma in infancy have been reported until 1992. We report an additional case of a huge choriocarcinoma of the liver in a 2-month-old boy, who died of tumor hemorrhage. This baby was born to a 19-year-old unmarried mother. The placenta was thought to be normal and was not examined histologically. The liver mass was first noted 2 weeks after birth, and he was admitted because of poor feeding and pallor. Before any therapy was instituted, he died of massive tumor bleeding. Autopsy revealed a huge hemorrhagic tumor mass with massive necrosis in the left lobe of the liver. Several nodular metastases were found only in the lung. The remainder was unremarkable except for bilateral cleft lip and palate. It is presumed that the choriocarcinoma in the liver could be either a primary tumor in the absence of any primary focus in the mother or the infant or a metastatic lesion from an occult choriocarcinoma of the placenta.     

Intraplacental Choriocarcinoma Associated with Viable Pregnancy: Pathologic Features and Implications for the Mother and Infant

Choriocarcinoma arising in the placenta, or intraplacental choriocarcinoma, has seldom been reported, particularly in the absence of maternal metastases. Reluctance to diagnose choriocarcinoma in the presence of chorionic villi can delay diagnosis; however, timely diagnosis of choriocarcinoma is prognostically important, both for the mother and infant. We report the clinicopathologic findings in five mothers and infants in whom choriocarcinoma was identified in the placenta. None of the mothers had a history of gestational trophoblastic disease in previous pregnancies. Three placentas were similar with a single small lesion grossly suggesting a small infarct; microscopically these consisted of infarcted areas surrounded by choriocarcinoma. These three mothers were unusual in that none had metastatic choriocarcinoma; two were treated with chemotherapy and remained disease-free; the third was lost to follow-up shortly following delivery. The remaining two mothers had known pulmonary metastases at time of delivery. One of these latter two placentas contained a large marginal lesion microscopically identified as choriocarcinoma. The fifth placenta had rare microscopic foci of choriocarcinoma, and sheets of necrotic choriocarcinoma were identified in “blood clot” submitted with the placenta. In four of the five cases the choriocarcinoma appeared to be arising from otherwise normal chorionic villi, and in no case was there invasion of the villous stroma. All of the infants survived, and none had evidence of choriocarcinoma. These cases support the concept that choriocarcinoma associated with otherwise normal pregnancy arises in the placenta and may be more common than reported. Received August 11, 1997; accepted December 8, 1997.     

ACID-BASE AND ELECTROLYTE BALANCE IN NEWBORN INFANTS OF DIABETIC MOTHERS

The acid-base and electrolyte balance was studied in 8 diabetic and 8 healthy mothers and their infants at caesarean section near term. Microliter methods were used for determination of pH, total CO₂, potassium, sodium, chloride, calcium, total protein, inorganic phosphorus, glucose and lactate. The acid-base and electrolyte balance of the newborn infant of a well-controlled diabetic mother did not differ significantly from that of a newborn infant of a healthy mother. The infant of a diabetic mother seemed to be able to correct for an excess load of glucose and to maintain a “normal” level in the blood in the umbilical artery. Earlier observations that intense maternal hyperventilation is associated with a changed uterine and placental circulation and results in fetal acidosis were not confirmed in the present study.     

Transient neonatal hypothyroidism in a neonate born of a mother with Hashimoto's thyroiditis

Transient neonatal hypothyroidism was found in a boy whose mother was treated for hypothyroidism due to Hashimoto's thyroiditis. During the neonatal period the infant had antithyroid microsomal and antithyroglobulin antibodies and immunoglobulins inhibiting cyclic AMP production by thyroid cells in vitro. After one year of treatment, all antibodies disappeared. Thyroid scintiscan and fixation in the neonatal period was negative and became positive 2 months after stopping treatment with normal fixation and cervical thyroid picture. The mother's serum contained the same antibodies: they crossed the placental barrier and were responsible for neonatal pathological manifestations.     

Short-term hyperthyroidism followed by transient pituitary hypothyroidism in a very low birth weight infant born to a mother with uncontrolled Graves' disease

Transient hypothyroxinemia in infants born to mothers with poorly controlled Graves' disease was first reported in 1988. We report that short-term hyperthyroidism followed by hypothyroidism with low basal thyroid-stimulating hormone (TSH) levels developed in a very low birth weight infant born at 27 weeks of gestation to a noncompliant mother with thyrotoxicosis attributable to Graves' disease. We performed serial thyrotropin-releasing hormone (TRH) tests in this infant and demonstrated that TSH unresponsiveness to TRH disappeared at 6.5 months of age. The maternal thyroid function was free triiodothyronine (FT(3)), 21.1 pg/mL; free thyroxine (FT(4)), 8.1 ng/dL; TSH, <0.03 microU/mL; thyroid-stimulating hormone receptor antibody, 52% (normal: <15%); thyroid-stimulating antibody, 294% (normal: <180%); and thyroid-stimulation blocking antibody, 9% (normal: <25%) on the day of delivery. A nonstress test revealed fetal tachycardia >200 beats per minute, and a male infant weighing 1152 g was born by emergency cesarean section. Thyroid-stimulating hormone receptor antibody was 16% and thyroid-stimulating antibody was 370% in the cord blood. We administered 10 mg/kg per day of oral propylthiouracil from day 1. Tachycardia along with elevated FT(4) and FT(3) levels in the infant decreased from 200/minute to 170/minute, 4.7 ng/dL to 2.9 ng/dL, 7.0 pg/mL to 4.8 pg/mL, respectively, in the first 33 hours. At 5 days, FT(4) and FT(3) were 1.1 ng/dL and 2.9 pg/mL, respectively, and we stopped propylthiouracil administration. Although FT(4) decreased to 0.4 ng/dL, TSH was quite low and did not respond to intravenous TRH by 14 days of age. We began daily levothyroxine 5-micro/kg supplementation. The responsiveness of TSH to TRH did not become significant until 4 months old and normalized at 6.5 months old. At this time, levothyroxine was stopped. We conclude that placental transfer of thyroid hormones may cause hyperthyroidism in the fetal and early neonatal periods and lead to transient pituitary hypothyroidism in an infant born to a mother with uncontrolled Graves' disease.     

Le choriocarcinome infantile : une tumeur exceptionnelle et curable

Choriocarcinoma is a malignant growth of trophoblastic cells characterized by secretion of human chorionic gonadotropin (hCG). Infantile choriocarcinoma is a very rare tumor, which is a complication of gestational choriocarcinoma and usually had very poor prognosis before chemotherapy was used. We report 1 new case as well as a review of the literature since 1945. Our case report describes the successful treatment by chemotherapy of a newborn with cerebral metastasis. Several features are important: Infantile choriocarcinoma occurs in infants aged 0 to 6 months. Anemia, hepatomegaly and hemorrhagic syndromes are the main symptoms with sometimes cerebral, cutaneous or ear-nose and throat localisations. But diagnosis can be difficult when clinical symptoms are poor. The main diagnostic criterion is a very high plasmatic or urinary level of hCG or beta-hCG in the newborn. Histological pattern is not mandatory for diagnosis. Thoracoabdominal CT scan and cerebral MRI are necessary to find metastases. Recommended treatment is chemotherapy and surgery is discussed when a tumoral residue remains. Post-treatment surveillance is based on clinical and radiological examination as well as negativation of beta-hCG. Choriocarcinoma occurring simultaneously in mother and child have been reported. Therefore it is necessary to assay maternal serum beta-hCG when infantile choriocarcinoma is disclosed and to assay serum beta-hCG in the newborn when the mother has gestational choriocarcinoma. Infantile choriocarcinoma is a very chemosensitive tumor and is thereby potentially curable. Early diagnosis is the most important prognostic factor.     

Placental weight and its ratio to birthweight in a Ukrainian city

BACKGROUND: Placental weight and its ratio to birthweight have recently been reported to predict later chronic disease. These fetal growth indicators have been measured in the west for over a century with consistent results when methods of preparation were comparable. We investigated whether recent difficult conditions in the former eastern bloc have altered placental weight or its relationship to other fetal size measures from what has historically been reported. METHODS: Placentas were obtained from 1621 singleton births of at least 28 weeks gestation in a Ukrainian city during 1993-1994, using a systematic protocol. Maternal characteristics were obtained from questionnaires. Pregnancy complications and birth size measures (infant weight, length, crown-rump length, and head circumference) were abstracted from medical records. We examined relationships of placental weight and ratio to these variables. RESULTS: Placental weight ranged from 100 to 1000 g, with a mean of 470 g. Mean placental ratio was 13.9%. Placental weights increased and ratios decreased with gestational age. Larger ratios were related to larger maternal BMI. Absolute measures of infant size and placental weight were mutually positively correlated. Placental ratio, infant length, and ponderal index (PI) were nearly uncorrelated. CONCLUSIONS: Absolute and relative weights of Ukrainian placentas were similar to historical reports, as were their relationships to other infant size indicators. Placental weight ratio (PWR), ponderal index, and infant length measured different birth size dimensions. Placental availability, consistency of placental measurements, and placental ratio's reflection of an independent facet of fetal growth make the placenta a useful research tool.     

Dysmorphic Villi Mimicking Partial Mole in a Case with del(18)(q21)

In this article, we report the histopathologic findings in a placenta from an early second trimester abortion. The placental villi showed prominent scalloping with many intravillous trophoblastic pseudoinclusions and mild trophoblastic hyperplasia, mimicking the morphology of partial hydatidiform mole. The placental karyotype was 46,XY,del(18)(q21). These histopathologic changes have been previously described in numerical chromosomal aberrations like triploidy, tetraploidy, and trisomies, but not in structural chromosomal abnormalities.     

Salivary gland neoplasms in children: the experience of the Istituto Nazionale Tumori of Milan

BACKGROUND: Epithelial salivary gland tumors are very uncommon in pediatric age. We report a series of 52 cases treated at the Istituto Nazionale Tumori of Milan, Italy, over a 30-year period. These results are presented in conjunction with a literature review of salivary tumors with a view to providing an up-to-date overview of the clinical course, prognosis, and treatment options for this rare tumor. PROCEDURE: Fifty-two cases of epithelial salivary tumors were reviewed and the clinical-pathological information concerning tumor characteristics, therapy, and follow-up were collected. Patients' age ranged between 4 and 18 years. RESULTS: The major salivary glands were the main site of tumor occurrence (79% of cases arose in parotid glands); 37 patients had benign tumors (pleomorphic adenoma), 15 had malignant tumors (12 mucoepidermoid carcinoma, 9 low grade). All the patients were treated by surgery; local relapses after parotidectomy were 4% and 25%, in benign and malignant tumors, respectively. When tumor enucleation was performed, recurrences occurred in 50% of benign neoplasms. At the time of the report, all patients with benign tumors were alive, 35(95%) without evidence of disease; only one patient with malignant tumor died of disease. CONCLUSIONS: Epithelial salivary glands tumor in children had different characteristics compared with their adult counterpart with respect to the frequency of histotypes and site of occurrence, but their prognosis seems to be similar. Parotidectomy (total or superficial) is the best choice for achieving good cure rates in both benign and malignant tumors.