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PATHOLOGY OF CHILDHOOD PATHOLOGY OF PREGNANCY Institute of Pathological Anatomy FM CU Wilms‘ tumor, neuroblastoma, ALL, hyaline membrane disease, remnants after pregnancy, extrauterine gravidity, hydatiform mola, choriocarcinoma
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Page 1: PATHOLOGY OF CHILDHOOD PATHOLOGY OF PREGNANCY

PATHOLOGY OF CHILDHOODPATHOLOGY OF PREGNANCY

Institute of Pathological Anatomy

FM CU

Wilms‘ tumor, neuroblastoma, ALL, hyaline membrane disease, remnants after

pregnancy, extrauterine gravidity, hydatiform mola, choriocarcinoma

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Disclaimer

Please note, that the following information is intended just

for educational purposes of the medical students at Faculty of Medicine, Comenius

University.

All copyrights belong to their owners and

are used here for educational purposes only.

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PATHOLOGY OF CHILDHOOD

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CASE NO. 1

• 4-year-old boy was admitted to the hospital for palpableresistance on the right side of the abdomen

• previously, there were episodes with intermittent hematuria with blood clots, and the child cried with each urination

• the boy was the second child of three siblings, pregnancy and childbirth without complications

• the child has never been admitted to a neonatal intensive care unit, was without neonatal sepsis or jaundice. The boy was breastfed for one year.

• developmental milestones were appropriate to his age, vaccinated according to the vaccination calendar

• the first symptom occurred on the right side of the abdomen; small palpable resistance, which stareted to increase rapidly, asymmetrically positioned

➢ Suggested examinations?

➢ Your diagnosis?

➢ Complications?

➢ Describe the histological finding.

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Large solitary mass that compresses the renal parenchyma; soft consistency, lobular appearance with areas of necrosis and bleeding.

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Nephroblastoma

Immature mesenchymal

component - spindle-

shaped sarcomatoid cells

Nephroblastic tissue - small

blue cells

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Nephroblastic tissue - small

blue cells

Immature mesenchymal

component - spindle-

shaped sarcomatoid cells

Immature epithelial

component - primitive

tubules and glomeruli

Nephroblastoma

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NEPHROBLASTOMAWILMS' TUMOR

• 4. most common malignancy of childhood (1-4 years)

• sporadic occurrence

• pathogenesis is unknown - genetically determined (p53, WT2 and gene on chromosome 11 WT1)

• microscopically three-phasic appearance

Undifferentiated blastema - primitive embryonic nephroblastic tissue

Differentiating epithelial structures - primitive tubules and glomeruli

Mesenchymal structures - muscle, adipose, fibrous tissue, cartilage, bone

➢ the presence of anaplastic changes is a sign of a worse prognosis regardless of staging

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CASE NO. 2

• 7-year-old boy was sent to a hospital due to persistent back pain for two months. The pain increased as he walked, but disappeared as he rested. Lately he is more sleepy and tired, you find petechiae on the skin of the chest.

• breathing, TT and heart rate corresponded to age (26 breaths / min, TT - 37°C, heart rate 96 / min)

• conjunctivae were pale, you notice enlarged lymph nodes in the inguinal region, LN were mobile to the base, painless

• without hepatosplenomegaly, without rash and swelling of the limbs

• blood count – leukocytosis (for a month)

➢ Suggested examinations?

➢ Your diagnosis?

➢ Complications?

➢ Describe the histological finding.

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Small to medium cells, scarce cytoplasm, high N: C ratio, diffuse granular chromatin,

unrecognizable nucleoli, mitotic figures

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ACUTE LYMPHOBLASTIC LEUKEMIA

• group of clonal disorders characterized by proliferation and accumulation of lymphoblasts (T and B lymphoblasts)

• the most common cancer in children under 4 years

• massively affects the bone marrow with releasing into the peripheral blood

• possible formation of extramedullary mass - lymphoblastic lymphoma

• B-ALL: (90%) KD, peripheral blood (preschool age, good prognosis)

• T-ALL: (10%) thymus (young adults, men, worse prognosis)

Etiology

• associated with EBV and HIV infection

Diagnostics

• peripheral blood and bone marrow smear, immunophenotyping and molecular analysis

➢ the presence of the Philadelphia chromosome is a negative prognostic feature

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CASE NO. 3

• at the regular gynecological examination you performed a USG of the fetus with an oligohydramnios

• at week 36, the pregnancy was terminated by caesarean section

• after birth, motor insufficiency of the lower limbs and constant leaking of urine were noted

➢ Suggested examinations?

➢ Your diagnosis?

➢ Complications?

➢ Describe the histological finding.

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NEUROBLASTOMA

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• The tumor responded well to chemotherapy, but the neurological deficit improved only slightly and the bladder dysfunction remained unchanged.

• At the age of 2 years, the patient is able to walk with leg orthoses, suffers from chronic constipation requiring daily medication and has a neurological bladder requiring repeated daily catheters.

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Neuroblastoma

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Neuroblastoma - streaks of cells separated by a fibrovascular stroma

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*

differentiating

ganglion cell

immature

neuroblasts

Neuroblastoma - small round cells, little cytoplasm, hyperchromasia

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NEUROBLASTOMA• tumor from primitive cells derived from the neural crest

• the most common extracranial solid tumor in children (up to 5 years)

• clinical signs are non-specific (failure to thrive, fever, anemia, limb pain, increased blood pressure)

• 2/3 of children have metastases at the time of diagnosis

Localisation

• adrenal medulla, along the paraaortic sympathetic nervous system (retroperitoneally)

Variants according to the degree of differentiation

1. Undifferentiated neuroblastoma

2. Low differentiated neuroblastoma

3. Differentiating neuroblastoma

➢ prognosis depends on tumor differentiation, genetic changes (amplificationof N-MYC gene, DNA ploidy in tumor) and biochemical symptoms (elevatedLDH and ferritin levels)

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↑ n-myc amplification (FISH detection)

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CASE NO. 4

• 25-year-old woman, primigravida, gave birth in the 29th week

• mother has no known diseases, the major perinatal factors affecting pregnancy are unknown

• child 2.05 kg, Apgar score 8/10, weaker neonatal reflexes, respiratory rate 40 / min

• crying weakened after a few minutes, the baby began to be cyanotic, the Moro reflex gradually disappeared, breathing is irregular

• auscultatively crepitations, irregular breathing with apnoeic pauses are present

➢ Your diagnosis?

➢ Complications?

➢ Describe the histological finding.

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On the second day of life, a premature baby in the 29th week of pregnancy develops progressive respiratory distress.

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HYALINE MEMBRANE DISEASEINFANT RESPIRATORY DISTRESS SYNDROME

• occurs in immature neonates who do not have sufficiently developed type 2 pneumocytes producing surfactant (surface active factor - antiatelectic effect)

• surfactant synthesis is reduced by maternal DM, cesarean delivery

• the most significant disorder of postnatal adaptation

• in the absence of surfactant there is a decrease in the functional capacity of the lungs with hypoventilation and hypoxia -> vasoconstriction and hypoperfusion of the lungs ->damage to the endothelium of capillaries with damage to the alveolar lining (necrosis) -> formation of the hyaline membrane

Prognosis

• death (20 - 30%), resolution, interstitial pneumonia, interstitial fibrosis

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PATHOLOGY OF PREGNANCY

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CASE NO. 5

• 26-year-old primigravida, 18th week, regularlyattends a counseling center, without complications, genetic screening turned out to be negative.

• came to the hospital for vaginal bleeding and cramping abdominal pain

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villus

Deciuda cells:

Puffed endometrial stromal cells rich in light

cytoplasm resembling epithelia

villi

decidua

Remnants after miscarriage

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Remnants after miscarriage

decidua

Hypersecretory endometrium

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REMNANTS AFTER MISCARRIAGE

➢ Abortion = early termination of pregnancy

Abortion classification: induced / spontaneous• anembryomola• complete / incomplete abortion• missed abortion• imminent abortion• recurrent abortion

EtiologyMaternal factors: inflammatory and circulatory disorders of the placenta, toxic, mechanical and mental insults, endometrial, hormonal and immune diseases Fetal factors: predominantly chromosomal aberrations

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CASE NO. 6

• 33-year-old patient was admitted to a gynecological clinic forprolonged vaginal bleeding without abdominal pain.

• last period was 42 days ago

• did not use any form of contraception. The patient had no IUDs in thepast, did not take any fertility drugs, and did not have pelvic surgery

• physical examination - 107/55 mmHg and pulse frequency 88 / min,abdomen soft, without pain on palpation

• the serum p-HCG level was 6993.1 IU / l and the progesterone levelwas 13.40 μg / l

➢ Suggested examinations?

➢ Your diagnosis?

➢ Complications?

➢ Describe the histological finding.

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Extrauterine pregnancy

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• Based on β-HCG and USG, you assume a diagnosis of ectopic pregnancy and yourpatient has been admitted to the gynecology department

• When being admitted to hospital, her serum p-HCG level increased to 13721.3 IU/l

• A wedge resection of the right uterine horn and a partial (isthmus) resection of theright fallopian tube were performed.

• Her serum β-HCG level was 7373.5 IU / l the first day after surgery and increasedto 10522.3 IU / l the next day.

• The levels of β-HCG and progesterone continued to increase over the next few days

➢ Next approach?

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Extrauterine pregnancy

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Tube lumen

Chorionic villi with trophoblast

Extrauterine pregnancy

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EXTRAUTERINE PREGNANCY

• embryo implantation outside of the uterine cavity• makes up about 1-2% of pregnancies• 1 in 1580 extrauterine pregnancies are bilateral

Localisation90% tube, uterine horns, ovary, cervix, abdominal cavity

Etiologyobstacle during the transfer of a fertilized egg to the uterus - inflammatorydiseases of the small pelvis, chronic salpingitis, adhesions, endometriosis, previous surgery of the fallopian tubes, intrauterine contraceptives, congenitalanomalies of female genitals, ...

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CASE NO. 7

• 29-year-old patient comes for regular check-up, complains of unusual menstrual bleeding lasting 3 days, abdominal cramps, nausea, vomiting and low back pain, last menstruation 5 weeks ago.

• lives with a partner as they use the calendar method of contraception

• active smoker, without allergies, does not drink alcohol

• physical examination - TT 37 ° C, BP 119/64 mmHg, heart rate 123 / min, respiratory rate 16 / min, O2 saturation 98%, peripheral filamentous pulse, hands sweaty, cold.

• cervical dilatation, with bleeding and excretion of brown-colored material and blood clots

• laboratory hemoglobin 8.6 g / dl, hematocrit 7.5%, white blood cell count 16,000, platelets 123,000, β-HCG was 360,514 mIU / ml.

➢ Your diagnosis?

➢ Complications?

➢ Describe the histological finding.

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Complete hydatidiform mole - cystically degenerated villi filled with fluid reaching a diameter of 1 - 30 mm

(appearance of bundles of grapes)

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Cystically dilated avascular villus

Circular proliferation of trophoblast

Complete hydatidiform mole

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Avascular villus

with hydropic

degeneration

Trophoblast

proliferation with

HCG production

Complete hydatidiform mole - HCG

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MOLA HYDATIDOSAGESTATIONAL TROPHOBLASTIC DISEASE

• part of gestational trophoblastic disease - a group of pathological units characterized by abnormaltrophoblast proliferation

• non-tumor proliferation of the villous trophoblast due to impaired ovarian fertilization

• 1: 1000 (mainly before the age of 20 and after the age of 40)

Types

• Complete - 46 XX, 46 XY - diploid, without maternal set of chromosomes

• Partial -69 XXX, 69 XXY, 69 XYY (rare) - triploid, both maternal and paternal set of chromosomes

• Invasive - based on complete or partial mola with the ability of infiltration of chorionic villi into themyometrium

Diagnostics

• USG without evidence of fetus in the uterus, elevated urinary hCG levels

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23X

23X/Y

23X/Y

23X/Y

23X/Y

Complete mole:

Partial mole:

dispermy

dispermy

23X

Empty ovum

Empty ovum

46XX

Duplication of

chromosomes Homozygous

complete mole

46XX

46XY

69XXX

69XXY

69XYY

Heterozygous

complete mole

Triploid partial

mole

rare

(46YY is not

compatible with

life)

MOLA HYDATIDOSAGESTATIONAL TROPHOBLASTIC DISEASE

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Invasive hydatidiform mole - infiltration into myometrium

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myometrium

myometrium

Hydropic villus with

trophoblast proliferation

growing into myometrial

structures

Invasive hydatidiform mole - infiltration into myometrium

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CASE NO. 8

• 29-year-old woman, after 2 childbirths; 4 months after giving birth was admitted to hospital for massive vaginal bleeding, severe anemia, high feverand a cough

• Lung X-ray confirmed tumorous changes, whole-body CT confirmed metastases in the lower thirds of the vagina

• the βHCG score was 31030 IU / ml

➢ Your diagnosis?

➢ Complications?

➢ Describe the histological finding.

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Choriocarcinoma

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Bizarre trophoblast

cells without villi

Hemorrhages

Choriocarcinoma - without villi, bizarre syncytio- and cytotrophoblast, bleeding, necrosis, invasive growth into the myometrium,

invasion into blood and lymphatic vessels

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Bizarre trophoblast

cells without villi

Choriocarcinoma

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Choriocarcinoma – IHC for presence of HCG

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• Four chemotherapy courses were started postoperatively.

• The development of the case was favorable, with normalization of βHCG levels two months after surgery and complete remission of metastases six weeks after surgery.

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GESTATIONAL CHORIOCARCINOMAGESTATIONAL TROPHOBLASTIC DISEASE

• malignant tumor arising from syncytiotrophoblast and cytotrophoblast cells without the presence of

chorionic villi with the development of distant metastases to the brain, lung and liver

• anaplastic tumor with marked cytological atypia and high mitotic activity with atypical mitoses

Etiology

• Hydatiform mole (50 %)

• Spontaneous abortion (25%)

• Normal pregnancy (20%)

• Ectopic pregnancy (5%)

Prognosis: with hysterectomy and chemotherapy, 70% of patients are cured, death occurs due to bleeding

from sites of metastasis to the CNS or lungs

➢ gestational choriocarcinoma is characterized by high sensitivity to chemotherapy in contrast to germinal

choriocarcinoma

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SUMMARY

• childhood tumours make up more than 2/3 of cancers

• the most common tumours of childhood grow from undifferentiated tissues (0-5 years), connective tissue and bones (adolescence)

• Acute lymphoblastic leukaemia (ALL) is the most common malignancy in children

• neuroblastoma is the most common extracranial solid tumour in children

• they are often part of genetic syndromes

• choriocarcinoma is a trophoblast-based tumour

•choriocarcinoma can be a germinal tumour or as part of a gestational trophoblastic disease

•hydatidosis occurs when the fertilization of the egg is impaired


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