Pathology

Various techniques can be utilized to examine fetal and placental tissues:

 

Gross Examination

 

The foremost task is to visually inspect the fetus or its individual parts. Ideally, a comprehensive examination of an intact fetus provides the most valuable insights, but even scrutinizing fetal components can yield valuable information.

 

The presence of significant physical irregularities can frequently hint at potential chromosomal anomalies or syndromes. These anomalies may sometimes be quite subtle, especially in cases of early gestational age.

 

To assess the findings, consultations are sought from clinical geneticists. A detailed description of the observations is documented in a report, which can be either a surgical pathology report or an autopsy report.

 

Examining the placenta holds great significance since fetal loss may be attributed to issues with the placenta itself.

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Microscopic Examination

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Microscopic observations are typically less informative than a macroscopic assessment when it comes to examining the fetus. However, it's crucial to conduct microscopic examinations of the placenta. Microscopy can assist in assessing gestational age (maturity of the lungs and kidneys), detecting infections, identifying neoplastic growths, and detecting any abnormalities in organ development referred to as "dysplasia."

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Radiography

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The utilization of standard anterior-posterior and lateral radiographic perspectives is crucial for the examination of the fetal skeleton. Radiographic imaging serves as a valuable tool for making comparisons with prenatal ultrasound when there are restrictions on obtaining autopsy consent. It aids in identifying anomalies and pinpointing specific areas for microscopic examination. Postmortem radiography can be instrumental in diagnosing various conditions, including:

 

• Abnormalities in the skeletal structure (such as dwarfism, dysplasia, sirenomelia, etc.).

• Neural tube defects (like anencephaly, iniencephaly, spina bifida, etc.).

• Osteogenesis imperfecta-related issues (such as osteopenia and fractures).

• Alterations in soft tissues (including hydrops, hygroma, etc.).

• The presence of teratomas or other types of neoplasms.

• Growth retardation.

• Verification and assessment of fetal body parts (particularly with D&E specimens).

• Evaluation of catheter or therapeutic device positioning.

 

Microbiologic Culture

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Culture can assist in the diagnosis or verification of congenital infections. Instances of congenital infection encompass:

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    T - toxoplasmosis

    O - other, such as Listeria monocytogenes, group B Streptococcus, syphilis

    R - rubella

    C - cytomegalovirus

    H - herpes simplex or human immunodeficiency virus (HIV)

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Serologic testing is an available option for diagnosing many of these infections, and it can be conducted using maternal serum. These tests can detect both IgM antibodies, indicating recent infections that might affect the fetus, and IgG antibodies, suggesting past infections. Higher antibody titers indicate a higher likelihood of potential fetal involvement.

 

To accurately diagnose agents like E. coli or group B streptococcus, proper cultures must be obtained using the correct media and submitted with the appropriate requisitions. The term "routine" includes testing for aerobic and anaerobic bacteria, while fungal and viral cultures must be specifically requested.

 

Viral cultures are challenging and costly, often requiring separate media and collection procedures based on the specific virus being targeted.

 

Contamination by bacteria can pose a significant issue.

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Karyotyping

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Tissues should be acquired in their freshest state possible and without any contamination when intended for culture. A valuable approach involves rinsing postmortem tissue samples in sterile saline before introducing them into cell culture media. Tissues that are less macerated, such as the placenta, lung, and diaphragm, tend to offer the highest likelihood of successful growth. To enhance yield and prevent contamination or detect mosaicism, obtaining tissue from multiple sites can be beneficial.

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FISH (performed on fresh tissue or paraffin blocks)

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Besides karyotyping, fluorescence in situ hybridization (FISH) offers another valuable option. Numerous types of probes are at one's disposal, making it a valuable tool for identifying aneuploid conditions such as trisomies and monosomies.

 

Although it is preferable to work with fresh cells, this method can also be applied to fixed tissues stored within paraffin blocks. However, dealing with paraffin blocks is considerably more time-consuming, and the interpretation of results can pose challenges. The capacity to employ FISH with paraffin blocks enables the examination of archived tissues in situations where karyotyping wasn't conducted or when cell cultures failed to develop.

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• FISH technique, diagram

• FISH abnormalities, diagram

 

DNA Probes

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Fetal cells acquired through amniocentesis or CVS can undergo DNA sequence analysis. In certain instances, when the DNA sequence of a gene is known, it is feasible to utilize a probe specific to a genetic marker's DNA sequence, and the polymerase chain reaction (PCR) technique can be employed for diagnostic purposes.

 

While there are numerous types of birth defects, only a minority of them have had specific genes identified, with tests developed for some of them. Consequently, it is not always feasible to identify a particular genetic anomaly for all birth defects. Additionally, the testing process can become more intricate due to the potential presence of various mutations within the same gene.

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Biochemical Analysis

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Tissues can be procured for cell cultivation or for the extraction of substances that may assist in detecting inborn metabolic disorders. Instances include:

• long-chain fatty acids (adrenoleukodystrophy)

• amino acids (aminoacidurias)

 

Flow Cytometry

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Flow cytometry is exclusively valuable for quantifying DNA content and cannot provide insights into individual chromosomes affected by aneuploidy. Consequently, flow cytometry reliably identifies triploidy as the sole detectable condition. It demands a minimal sample size of just 0.1 grams and is adaptable for use with preserved tissues within paraffin blocks.

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Electron Microscopy (EM)

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Electron microscopy (EM) is infrequently employed and necessitates immediate attention without any tissue softening. Instances of conditions that can be identified through EM consist of:

• mitochondrial myopathies

• viral infections