Test ID: POC
Chromosome Analysis, Autopsy, Products of Conception, or Stillbirth

Autopsy:

-Second-tier testing for chromosomal abnormalities

-Follow-up testing when chromosomal analysis and other studies on peripheral blood are inconclusive or when peripheral blood quality is poor or sampling is not possible

Products of Conception or Stillbirth:

-Diagnosing chromosomal causes for fetal death

-Determining recurrence risk for future pregnancy losses

If the chromosome study fails to produce dividing cells, this test will be resulted at no charge, and FPOCR/29924 Aneuploidy Detection, Products of Conception (POC) Reflex, FISH will be performed.

• Final Disposition of Fetal/Stillborn Remains
• Informed Consent for Genetic Testing

POC/8887: Includes 2 banded karyograms analysis of 20 or more metaphases, and other techniques when required.
FPOCR/29924: Fluorescence In Situ Hybridization (FISH) with DNA Probes

Provide a reason for referral with each specimen. The laboratory will not reject testing if this information is not provided, but appropriate testing and interpretation may be compromised or delayed.

In POC specimens, maternal cell contamination can interfere with the interpretation of chromosome analysis. To reduce this difficulty, attempt to identify and send only fetal tissue for analysis. If multiple specimen types are sent, send each specimen in a separate container. Multiple specimens received (eg, placenta and fetal thigh) will be ordered under 1 test. All specimens will be processed separately.

Forms:

1. New York Clients-Informed consent is required. Please document on the request form or electronic order that a copy is on file. An Informed Consent for Genetic Testing (Supply T576) is available in Special Instructions.

2. If not ordering electronically, submit a Cytogenetics/AFP Congenital Disorders Request Form (Supply T238) with the specimen.

Advise Express Mail or equivalent if not on courier service.

Preferred:

Specimen Type: Products of conception or stillbirth

Container/Tube: Sterile container with sterile Hank's balanced salt solution (Supply T132), Ringer's solution, or normal saline

Specimen Volume: 1 cm(3) of placenta (including 50-mg chorionic villi) and 1 cm(3) biopsy specimen of muscle/fascia from the thigh

Collection Instructions: If a fetus cannot be specifically identified, collect 50-mg villus material or tissue that appears to be of fetal origin.

Additional Information:

1. Do not send entire fetus.

2. While fresher specimens prepared as described above are preferred, we can attempt analysis on specimens that have been in less-than-ideal conditions.

Forms: Final Disposition of Fetal/Stillborn Remains (if fetal specimen is sent) in Special Instructions.

Acceptable:

Specimen Type: Autopsy

Container/Tube: Sterile container with sterile Hank's balanced salt solution (Supply T132), Ringer's solution, or normal saline

Specimen Volume: 4 mm diameter

Collection Instructions:

1. Wash biopsy site with an antiseptic soap.

2. Thoroughly rinse area with sterile water.

3. Do not use alcohol or iodine preparations.

4. Biopsy specimens are best taken by punch biopsy to include full thickness of dermis.

Alternate:

Specimen Type: Chorionic villus

Container/Tube: 15-mL tube containing 15 mL of transport media

Specimen Volume: 50 mg

Collection Instructions:

1. Collect chorionic villus specimen (CVS) by transabdominal or transcervical method.

2. Transfer CVS to a Petri dish containing transport medium.             

3. Using a stereomicroscope and sterile forceps, assess the quality and quantity of villi and remove any blood clots and maternal decidua.

Chromosomal abnormalities may result in malformed fetuses, spontaneous abortions, or neonatal deaths. Estimates of the frequency of chromosome abnormalities in spontaneous abortuses range from 15% to 60%.

Chromosome studies of products of conception (POC) may provide useful information concerning the cause of miscarriage and, thus, the recurrence risk for pregnancy loss and risk for having subsequent children with chromosome anomalies.

Chromosome analysis of the stillborn infant or neonate (autopsy) may be desirable, particularly if there is a family history of 2 or more miscarriages or when malformations are evident. For neonatal cases, peripheral blood is the preferred specimen for chromosome analysis (CMS/8696 Chromosome Analysis, for Congenital Disorders, Blood).

46,XX or 46,XY. No apparent chromosome abnormality.

An interpretive report will be provided.

The finding of a chromosome abnormality may explain the cause of a miscarriage or stillbirth, particularly when the chromosome results show aneuploidy or an unbalanced structural rearrangement.

Some of the chromosome abnormalities that are detected in these specimens are balanced (no apparent gain or loss of genetic material) and may not be associated with birth defects, miscarriage, or stillbirth.

For balanced chromosome rearrangements, it is sometimes difficult to determine whether the chromosome abnormality is the direct cause of a miscarriage or stillbirth. In these situations, chromosome studies of the parents' peripheral blood may be useful to determine if an abnormality is familial or de novo.  

De novo, balanced rearrangements can cause miscarriages or stillbirth by producing submicroscopic deletions, duplications, or gene mutations at the site of chromosome breakage.

A normal karyotype does not rule out the possibility of birth defects, such as those caused by submicroscopic cytogenetic abnormalities, molecular mutations, and environmental factors (ie, teratogen exposure).

Due to bacterial contamination or nonviable cells, we are unable to establish a viable culture 20% of the time. In these cases, the specimen cannot be used for chromosome analysis, so the FISH aneuploidy test is automatically initiated. While the FISH test is not as comprehensive as a chromosome analysis, it can provide information with regard to many of the most common numeric abnormalities in spontaneous miscarriage and stillbirth.

Interfering factors

Technical:

-Lack of viable cells or bacterial contamination (this occurs in approximately 20% of spontaneously aborted products of conception)

-A long delay between fetal death and the miscarriage

-Excessive transport time

-Exposure of the specimen to temperature extremes

Biological:

-Subtle structural chromosomal abnormalities can occasionally be missed

-Culturing of maternal cells rather than fetal cells

-Chromosome mosaicism may be missed due to statistical sampling error (rare)

Dewald GW, Michels VV: Recurrent miscarriages: cytogenetic causes and genetic counseling of affected families. Clin Obstet Gynecol 1986;29:865-885

Autopsy:

The specimen is cleaned and cut into small pieces and treated with enzymes. The tissue is then placed into a dish with a coverslip. Cells are cultured with Chang and MEM-alpha-medium containing 20% fetal bovine serum and antibiotics to establish a fibroblast culture. After 5 to 14 days, the fibroblasts are exposed to colcemid, ethidium bromide, and hypotonic solution, and fixed with glacial acetic acid and methanol. Metaphase cells are dropped onto microscope slides and are routinely stained by G-banding, but other staining methods are frequently employed as needed. At least 20 metaphases are examined for structural and numeric chromosome abnormalities. Minimal evidence for the presence of an abnormality is defined as 2 or more metaphases with the same structural abnormality or chromosome gain (trisomy), or 3 or more metaphases lacking the same chromosome. Five to 10 metaphases are captured using a computer-based imaging system and karyograms are prepared from 2 or more representative metaphases. (Dewald GW: Chromosome study of autopsy tissue. In Current Methods of Autopsy Practice. 2nd edition. Edited by J Ludwig. Philadelphia, WB Saunders Company, 1979, pp 155-159)

Products of Conception or Stillbirth:

Fetal versus maternal tissue is identified whenever possible. This tissue is cut into small pieces and treated with enzymes. The tissue is then placed into a Petri dish with a coverslip. Cells are cultured with Chang and MEM-alpha-medium containing 20% fetal bovine serum and antibiotics to establish a fibroblast culture. After 5 to 14 days, the fibroblasts are exposed to colcemid, ethidium bromide, and hypotonic solution, and fixed with glacial acetic acid and methanol. Metaphase cells are dropped onto microscope slides and are routinely stained by G-banding, but other staining methods are frequently employed as needed. At least 20 metaphases are examined. Minimal evidence for the presence of an abnormality is defined as 2 or more metaphases with the same structural abnormality or chromosome gain (trisomy), or 3 or more metaphases lacking the same chromosome. Five to 10 metaphases are captured using a computer-based imaging system and karyograms are prepared from 2 or more representative metaphases.  (Dewald GW: Chromosome study of autopsy tissues. In Current Methods of Autopsy Practice. 2nd edition. Edited by J Ludwig. Philadelphia, WB Saunders Company, 1979, pp 155-159; Spurbeck JL, Carlson RO, Allen JE, Dewald GW:  Culturing and robotic harvesting of bone marrow, lymph nodes, peripheral blood, fibroblasts, and solid tumors with in situ techniques. Cancer Genet Cytogenet 1988;32:59-66, Lindor NM, Ney JA, Gaffey TA, et al: A genetic review of complete and partial hydatidiform moles and nonmolar triploidy. Mayo Clin Proc 1992;67:791-799)

Samples processed Monday through Sunday. Results reported Monday through Friday, 8 a.m.-5 p.m. CST.

88233-Tissue culture for skin/biopsy

88291-Interpretation and report

88299-Unlisted cytogenetic study (Refer to patient report to apply the appropriate CPT code below in place of this unlisted cytogenetic study CPT code)

Based on the total number of cells analyzed and counted, MML would recommend the following:

Chromosome analysis with less than 5 cells; CPT Code 88261 w/ modifier 52

Chromosome analysis with 5 to 14 cells; CPT Codes 88261, 88285

Chromosome analysis with 15 to 19 cells; CPT Code 88262

Chromosome analysis with 20 to 25 cells; CPT Code 88264

Chromosome analysis with more than 25 cells; CPT Codes 88264, 88285