Pathology

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Survey of Congenital Tumors in Perinatal Necropsies Peter Werb, James Scurry, Andrew Östör, Denys Fortune & Harold Attwood To cite this article: Peter Werb, James Scurry, Andrew Östör, Denys Fortune & Harold Attwood (1992) Survey of Congenital Tumors in Perinatal Necropsies, Pathology, 24:4, 247-253 To link to this article: https://doi.org/10.3109/00313029209068876

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Pathology (1992), 24, pp. 247-253

SURVEY OF CONGENITAL TUMORS IN PERINATAL NECROPSIES JAMESSCURRY,* ANDREW &TOR, DENYSFORTUNE AND HAROLD ATTWOOD

PETER W E R B , t

Department of Anatomical Pathology, The Royal Women’s Hospital and *Department of Pathology, The Mercy Hospital for Women, Melbourne, Victoria ?Deceased

Summary In an audit of 17,417 necropsies from 1939 to 1989 at the Royal Women’s Hospital, Melbourne, Victoria, 46 congenital tumors comprising 24 teratomas, 8 vascular tumors, 6 neuroblastomas, three rhabdomyomas, two mesoblastic nephromas, one thyroid adenoma, one hepatic adenoma and one cerebellar medulloblastoma were found. The teratomas were generally large tumors and, because of their size and location, incompatible with extrauterine life. Ten teratomas were associated with polyhydramnios, three with obstructed labour, five of the fetuses were hydropic and four had malformations at sites distant to the tumor. Twenty teratomas occurred in stillbirths, half of whom were macerated. The vascular tumors were associated with polyhydramnios in three cases and hydrops fetalis in two. The neuroblastomaswere all incidental findings. Four were intra-adrenal, one was an adrenal tumor which had metastasized to the liver and the remaining case was a small paravertebral lesion. Two of the three rhabdomyomaswere multiple and one of these occurred in a case of tuberous sclerosis. One of the mesoblastic nephromas occurred in a hydropic fetus who had the Arnold-Chiari malformation. The thyroid and hepatic adenomas were small incidental lesions. The cerebellar medulloblastoma had led to marked hydrocephalus. Congenital tumors have different incidence, presentation and behaviour than those in childhood or adult life. The association of congenital tumors with congenital malformations and hydrops fetalis should always be remembered. Key words: Congenital tumors, teratomas, vascular, neuroblastomas,

rhabdomyomas, mesoblastic nephromas, thyroid adenoma, cerebellar rnedulloblastoma, stillbirths. Accepted 20 July, 1992

INTRODUCTION Congenital tumors are defined as those present at birth. In addition, Berry has stated that any tumor presenting in the first three months of life can be regarded as congenital.’ They may be incidental findings, symptomatic or fatal, depending on their size and location. Certain tumors are associated with polyhydramnios, obstructed labour, pre-eclampsia, hydrops fetalis or fetal malformations. Classification may be difficult, as it is debatable whether some lesions are true neoplasms, malformations or hamartomas. For unknown reasons, congenital tumors usually behave differently than similar tumors in older children. Although congenital tumors are rare, their

unique features make them worthy of study. In this audit, we document the experience of congenital tumors in a large obstetric teaching hospital over 5 decades. MATERIALS AND METHODS The necropsy records of the Royal Women’s Hospital, Melbourne, Victoria, between the years 1939 and 1989, were searched for congenital tumors and tumor-like conditions such as cysts, nodules or masses. Congenital tumors were defined as macroscopic tumors present at birth or presenting in the first three mths of life.’ Forty-six cases of congenital tumors were found in 17,417 neonatal necropsies. During the period of the study there were approximately 340,000 births at the hospital. The following data were collected from the necropsy records: 1. whether liveborn or stillborn, 2. if liveborn, the duration of life, 3. if stillborn, whether macerated or not, 4. complications of pregnancy, 5 . macroscopic and microscopic descriptions of congenital tumors, 6 . presence of co-existent developmental abnormalities. All cases had the original hematoxylin and eosin sections avaiIable for study and/or paraffin blocks available for recutting further sections. Photographs of the macroscopic specimens had been taken in many cases and these were reviewed.

RESULTS The distribution of congenital tumors is given in Table 1.

Teratomas The sites of origin of 24 teratomas are given in Table 2. All but two of the teratomas came from 3 sites, the head and neck, mediastinum and sacrococcygeal region. Table 3 summarizes the clinicopathological findings of the teratomas. Thirteen teratomas caused complications of pregnancy: 10, polyhydramnios and three, obstructed labour. In the cases of obstructed labour, one required needling of hydrocephalus due to intracranial teratoma, in another, a large sacrococcygeal teratoma was avulsed during delivery (Fig. I), and in a third, the fetus exsanguinated due to tearing of a sacrococcygeal teratoma. Twenty teratomas occurred in stillbirths, half of whom were macerated. Four teratomas were associated with developmental anomalies at sites away from the teratoma. Case 2 had atrioseptal and ventriculoseptal defects, Case 4 had cleft lip and bilateral cleft palate, Case 13 had anencephaly, ventriculoseptal defect, pyloric stenosis and a single umbilical artery (Fig. 2), and Case 15, partial malrotation of the gut.

Pathology (1992), 24, October

Number

rypc _ _ _ I

T eratomas

24

Vaxular tumoi \ Neut oblastomai Rhabdomyoinata Mesoblastic n c p h r o m a s Thyroid a d e m m a \ Hepatic adenorn't Medulloblasioma Total

8 6 3 2 1

I 1

46

Head and neck 1 ntracranial Extracranial Sacrococcygeal Mediastinurn Retroperitoneurn Tesris Total

4

1 6 5 1 1

24

The teratomas were generally large, cystic and solid lesions with an average greatest dimension of 9 cm (Fig. 3). Histologically, the most common tissue components were neuroepithelium, skin, smooth muscle, respiratory epithelium, cartilage and mucous cysts. Although all teratomas, except the testicular teratoma, contained immature elements, principally neuroepithelial rosettes and immature neuroglia, none had metastasized. No other germ cell elements such as yolk sac were seen.

Vuscular rurnors Clinicopathological details of 8 cases with vascular tumors are given in Table 4. Four cases were associated with polyhydramnios, one with polyhydramnios and hydrops fetalis and one with hydrops alone. There were also three cases with malformations. T \iii

findings in 24 congenital teratomas -3 Cliiii~opathoiogtcal Size Sex

No

Ge\t

I

31

28 32

5

41 22

6

28

7

2' 29 29 ?

8 9 10 11

3.1

It

2X

13

33 25 31 29 40 33 24 34 23

14 15 16 17 18

1') 20 21

72 2.3 24

Neuroblastoma Four of the neuroblastomas were confined to the adrenal gland, Table 5. The other 2 neuroblastomas were an adrenal tumor with metastases and an extraadrenal neuroblastoma. The case of metastatic neuroblastoma occurred in a 42 wk gestation female infant who died at

L

3

3 4

Fig. 1 Sacrococcygeal teratoma. Large pedunculated tumor, the same size as the placenta, avulsed during delivery in a macerated fetus.

Age

F F F F F F F F F $1

51 F F t. I' 51 Yl

F F I-

MSR

SB MSB MSB

SB 1 hr MSR '/j hr SB hisn SB SB MSH 1 hr MSB MSB

MSB

33

MSB MSB MSR SB

44

>I

4 hrs

7 i

lntracranium Intracranium Intracranium Intracranium Extracranium Extracranium Extracranium Extracraniurn Extracranium Extracranium Extracranium Sacrococcygeus Sacrococcygeus Sacrococcygeus Sacrococcygeus Sacrococcygeus Sacrococcygeus Mediast inum Mediastinurn Mediastinum Mediastinum Mediastinurn Ret roperi t oneu m Testis

SB SB

I. 51 F

I_

1 Site

18 cm Large Large 3 cm 6 cm 9 cm I 1 cm 10 cm 15 cm 10 cm 14 cm 15 cm 6 cm 25 ern 14 cm 12 cm 19 cm 6 cm 2 ern 2 cm 37 g 4.5 ern 10 cm 2 cm

Preg comp

Fetal comp

PH PH

Malf

PH Vir hep PH PH PH

Malf Hydrops, Malf

Hydrops

PH PH Malf Ob lab Ob lab PH Hydrops Hydrops Hydrops Ob Lab

~

N o =case numbei , Cirat :-gestation (wks), Age = age of death, SB = stillbirih. hlSB =macerated stillbirth, Preg comp =pregnancy complications, Fetal comp = Feral complications. PH = polyhydramnios. O h lab = obstructed labour. Vir hcp = viral hcpatiiis, malf ---rnalformaiioii5.

CONGENITAL TUMORS IN PERINATAL NECROPSIES

Fig. 2 The coexistence of tumor and developmental anomalies is illustrated in this anencephalic fetus with a sacrococcygeal teratoma.

249

Fig. 3 Cervical teratoma. This tumor illustrates the typically large size and consequent deformity of most neonatal teratomas.

Fig. 4 Neuroblastoma. Haemorrhagic adrenal tumor associated with numerous small pale hepatic metastases.

250

Pathology (1992), 24, October

\%L R B c( rrl

T ZBLL 4 Clinicopathological findings in 8 congenital vascular tumors __

No

Preg comp

Fetal findings

Preeclampsia PH PH O b lab

Peripheral hemangiomas lower limbs, buttocks Retroperitoneal 1ymphangioma Hydrops, diffuse hemangioma of skin, muscle, mesentery, adrenals, thorax, lower neck Liver hemangiorna, 4 cm exomphalos Angiomas of floor of mouth, neck, kidney and brain cysts Liver hemangioma x 2, anencephaly, rachischisis, partial gut rnalrotation and single umbilical artery Hydrops, hemangiomas of skin and mesentery Cystic hygrorna of right axilla and chest

Gest

Sex

28

M

15 min

37

F

SB

32

M

MSB

33

M

MSB

37

F

SB

PH Rubella

33

M

MSB

PH

34

F

MSB

PH

29

M

MSB

6 hrs of age of respiratory failure due to extensive pulmonary hemorrhage. At autopsy the left adrenal gland (70 g) was replaced by neuroblastoma, the liver contained numerous metastases and there was microscopic neuroblastoma in the right adrenal, (Figs. 4,5). The extraadrenal neuroblastoma occurred in a 5 day old male infant who died of respiratory failure with evidence of meconium aspiration prior to and during delivery, resulting in hypoxic cerebral hemorrhages. The tumor was a 1 cm diameter nodule situated on the anterior surface of the body of the first lumbar vertebra.

Rhabdotnyonia The clinicopathological features of three rhabdomyomas are given in Table 6. Case 1 had stigmata of tuberous sclerosis, viz. cerebral tubers, renal cysts, hepatic fibrosis and splenic nodules. This case has been previously reported as the first case of tuberous sclerosis presenting as hydrops fetalis.* The malformations in the third case were meningoencephalocele, extroversion of the bladder, imperforate anus, cystic disease of the left kidney and talipes. All three cases showed the characteristic histological features of rhabdomyomas, viz. non-encapsulated tumors of large vacuolated cardiac muscle cells containing glycogen (Fig. 6). The multifocal nature of the tumor was evident in Cases 1 and 2. Meso blast ic nephroma Both mesobiastic nephromas occurred in stillbirths. One case occurred in a stillborn female of 33 wks gestation with hydrocephalus, Arnold-Chiari malformation and thoracolumbar meningomyelocele. The renal tumor measured 2 cm and was located in the lower pole of the

left kidney. The other case occurred in a stillborn male infant of 30 wks gestation. Delivery followed the development of acute polyhydramnios. The left kidney was replaced by an 8 x 6 x 4 cm fibrous tumor (Fig. 7). Both cases demonstrated the classical pattern of interlacing bundles of bland spindle-shaped cells merging at the periphery with renal parenchyma (Fig. 8). Islands of benign tubules were enclosed within the tumor. Neither case had cardiomegaly .

Thyroid adenoma, hepatic adenoma and rnedulloblastoma The thyroid tumor was a small Hurthle cell adenoma, discovered incidentally in an immature female infant who died of hypoxia following antepartum hemorrhage. The hepatic adenoma occurred in a term female stillbirth. Labour was induced following development of eclampsia. The baby died approximately 2 hrs before delivery and showed the effects of intrauterine hypoxia. The adenoma was a 0.5 cm round, tan, circumscribed, but not encapsulated, nodule of cords of hepatocytes without portal tracts or bile ducts. The medulloblastoma was cerebellar in origin and occurred in a hydrocephalic term male infant who survived 6 hrs. Hydrocephalus was diagnosed by ultrasound at 34 wks gestation. The tumor was a 1.2 cm diameter polypoid lesion arising from the midline of the upper part of the cerebellum and the roof of the 4th ventricle, obstructing the fourth ventricle. DISCUSSION As this study is a necropsy audit, any congenital tumor which was non-lethal in the neonatal period is excluded,

TABLE 5 Clinicopathological features of 6 congenital neuroblastomas No

Gest

Site

TABLE 6 Clinicopathological features of 3 congenital rhabdomyomata

I

Size ~~

1 7 *

3

31 40 34 26 42 ?

1nt ra-adrenal

13 hrs 6 hrs 6 hrs

Intra-adrenal I nt ra-adrenal Intra-adrenal Adrenal mass, Hepatic metastases Paravertebral

I cm 1.2 crn ? ? 70 8 I cm

I

I

I

No Gest Sex Age

I Fetal findings Multiple rhabdomyomata, tuberous sclerosis Single rhabdornyoma, incidental finding Multiple rhabdomyomata, multiple malformations, but no tubers

CONGENITAL TUMORS I N PERINATAL NECROPSIES

25 1

Fig. 5 Neuroblastoma. Small round dark nuclei, pale fibrillary matrix and distinctive capillary vasculature. Hematoxylin and eosin x 320.

Fig. 6 Cardiac rhabdomyoma. Microscopic lesion consisting of a circumscribed nest of altered glycogen-rich myocytes. Hematoxylin and eosin x 320.

unless it happens to be an incidental finding in fetuses and infants dying of other causes. Given this limitation, the incidence and distribution of congenital tumors is comparable to other studie~.~'"The overall incidence of congenital tumors was one per 379 neonatal necropsies. The tumors formed a natural division between large tumors incompatible with extrauterine life, particularly teratomas, and small incidental tumors, such as intraadrenal neuroblastomas. The commonest tumors were teratomas, 24/46 (57%) of the total. Teratomas were also the tumors associated with the majority of cases with polyhydramnios, obstructed labour, hydrops and fetal malformations. The first hint of a congenital tumor in pregnancy is often polyhydramnios. In this study 15/46 (33%) of congenital tumors presented with polyhydramnios. Most of these, 10/15 (67%), were in teratomas. Usually, the pathogenesis of polyhydramnios could be related to difficulties in the fetal swallowing mechanism, presumably leading to reduced absorption of amniotic fluid from the gastrointestinal tract. The swallowing problem was due either to central nervous system teratomas affecting the neurological control of swallowing or epignathus causing mechanical obstruction. Hydrops fetalis was present in 8/46 (17%) and was often associated with polyhydramnios. Hydrops occurred

in teratomas, vascular lesions and a case of rhabdomyomata associated with tuberous sclerosis. Hydrops in congenital tumors could theoretically be due to circulatory obstruction, leaky tumor vessels and in the case of the rhabdomyomata, cardiac dysfunction. In only a small minority of congenital tumors was obstructed labour recorded. An important finding was the association of malformations with congenital tumors in 9/46 (20%). The malformations occurred mainly in fetuses and infants with teratomata, but were also found in those with angiomata and rhabdomyomata. They were usually not caused by the tumor and were frequently in another system. Congenital malformations may result from an intrinsically abnormal developmental process or be secondary to extrinsic factors. The same agent may be both a teratogen and a carcinogen. Drugs, toxins, radiation, and infections have produced both malformations and cancers in animal and human embryo^.'^-'^ The known sequence of organogenesis indicates an insult in the first few wks of pregnancy. The large size of teratomas and the rare case where twinning is difficult to distinguish from teratomas supports an early insult. Although virtually all the teratomas contained immature elements, particularly immature neurepithelium, none had metastasized. In fact metastasizing congenital

252

WERE

Pathology (1992), 24, October

Fig. 8 Mesoblastic nephroma. Bland spindle cell proliferation with infiltrating border into renal cortex. Hernatoxylin and eosin x 320.

Fig. 7 Mesoblastic nephroma. Large pale solid tumor greatly expanding the left kidney.

teratoma is extremely are.'^,^^ None of the tumors contained other germ cell elements such as yolk sac tumor or embryonal carcinoma. Neuroblastoma is the commonest solid tumor presenting in infancy. I 6 . l 7 Although histologically similar to tumors in older children, the prognosis is much better as most cases in neonates spontaneously regress. Even with massive hepatic metastases as seen in one of our cases, a common finding in neonatal neuroblastoma, regression is usual. None of our patients died of neuroblastoma; in fact, all the neuroblastomas were incidental findings. Neuroblastomas may be associated with neonatal hypertension due to high circulating catecholamine levels. A case of neonatal hypertensive heart failure has been described with neuroblastoma." None of our Iiveborn cases had hypertension or cardiomegaly. Although a rare condition, mesoblastic nephroma is the commonest neonatal renal t ~ m o r . ' ~ "Poly~ hydramnios, which is a frequent association of mesoblastic nephroma, was noted in one of our two cases.*' Recently, polyhydramnios in a case of mesoblastic nephroma has been shown to be due to increased fetal urine flow.21 Congenital mesoblastic nephroma is also associated with hypertension in which high renin levels have been

recorded.22 Both our cases were stillborn, but neither had cardiomegaly . Rhabdomyoma is virtually the only type of congenital tumor found in the heart23and most are multiple. Infrequently, hydrops fetalis has been reported with rhabdomyoma.2 Depending on the location of the rhabdomyomata, hydrops may be due to poor ventricular contractility or compliance, outflow obstruction or tachyarrhythmia. There is a strong association of cardiac rhabdomyomata with tuberous sclerosis. With echocardiography 50-64% of cases of tuberous sclerosis have been shown to have rhabdomyomata, whilst conversely 50% or more of cases of multiple rhabdomyomata are associated with the stigmata of tuberous sclerosis.24With imaging techniques, asymptomatic relatives of patients with tuberous sclerosis have been shown to have cerebral tubers.25 Given this information, genetic counselling and family investigation are advised if cardiac rhabdomyomata are discovered at autopsy. A recent development has been the accurate prenatal diagnosis of rhabdomyomata with echocardiography .26 Although there are rare reports of congenital thyroid carcinoma, we can find no reference to a congenital thyroid adenoma. Some of the congenital thyroid carcinomas are regarded as possibly dyshormonogenetic goitres. The commonest congenital liver adenomas are vascular tumors, hepatoblastoma and mesenchymal hamartomas. Hepatic adenomas have rarely been reported in children and very rarely in neonates.27 Congenital brain tumors are relatively uncommon in infants compared with those later in childhood. They are more likely to be supratentorial rather than infratentorial and medulloblastoma makes up only a small proportion. Although not seen in our case, congenital brain tumors, including medulloblastoma, are occasionally associated with malformations, which may be within or outside the central nervous system.28 Addressfor correspondence: A.G.O., Department of Anatomical Pathology, The Royal Women's Hospital, 132 Grattan Street, Carlton 3053, Victoria.

CONGENITAL TUMORS I N PERINATAL NECROPSIES

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