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Official Description

In situ hybridization (eg, FISH), per specimen; each multiplex probe stain procedure

© Copyright 2025 American Medical Association. All rights reserved.

Common Language Description

In situ hybridization (FISH) is a sophisticated laboratory technique utilized to identify and localize specific nucleic acid sequences, including DNA and RNA, within fixed tissues or cells. This method provides critical temporal and spatial information regarding gene expression and genetic coding, which is essential for understanding the organization, regulation, and functional roles of genes within biological systems. The process begins with the fixation of sample cells or tissues, which preserves the target transcripts in their original locations. Following fixation, a DNA or RNA probe is introduced, which hybridizes, or binds, to the target nucleic acid sequence at an elevated temperature. This step is crucial as it ensures that the probe specifically attaches to the intended target, allowing for accurate detection. After hybridization, any unbound excess probe is washed away, leaving only the bound probes attached to the target sequences. The remaining DNA or RNA targets are then stained using spectrally distinct fluorophore labels, which facilitate visualization under fluorescent microscopy. The FISH technique is versatile, allowing for the simultaneous use of multiple probes to visualize co-locations of different targets within a single specimen. This capability is particularly valuable in various applications, including gene mutation analysis and the assessment of gene expression patterns. For coding purposes, CPT® Code 88365 is designated for the initial single probe stain per specimen, while CPT® Code 88364 is used for each additional single probe stain. CPT® Code 88366 is specifically reported when multiple probes are employed in the same staining procedure, reflecting the complexity and depth of analysis provided by this technique.

© Copyright 2025 Coding Ahead. All rights reserved.

1. Indications

The in situ hybridization (FISH) technique is indicated for various diagnostic and research purposes, particularly in the following scenarios:

  • Gene Mutation Analysis This procedure is utilized to detect specific mutations in genes, which can be critical for diagnosing genetic disorders or cancers.
  • Gene Expression Studies FISH is employed to assess the expression levels of specific genes within tissues, providing insights into cellular function and regulation.
  • Copy Number Variation Assessment The technique helps in determining the presence and number of gene copies, which is essential in understanding genetic abnormalities.
  • Localization of RNA RNA-FISH is used to visualize the spatial distribution of RNA molecules within cells, aiding in the study of gene expression dynamics.

2. Procedure

The in situ hybridization (FISH) procedure involves several critical steps to ensure accurate localization and visualization of nucleic acid targets:

  • Step 1: Sample Preparation The first step involves obtaining tissue or cell samples, which are then fixed to preserve the cellular architecture and nucleic acid integrity. This fixation process is essential for maintaining the spatial relationships of the target sequences within the sample.
  • Step 2: Probe Hybridization Following fixation, specific DNA or RNA probes are introduced to the sample. These probes are designed to bind to complementary sequences of the target nucleic acids. The hybridization occurs at an elevated temperature, which facilitates the binding of the probes to their respective targets.
  • Step 3: Washing After hybridization, the sample undergoes a washing process to remove any unbound or excess probes. This step is crucial to enhance the specificity of the signal, ensuring that only the probes that are bound to the target sequences remain attached.
  • Step 4: Staining The bound DNA or RNA targets are then stained with spectrally distinct fluorophore labels. This staining allows for the visualization of the targets under fluorescent microscopy, enabling researchers to observe the location and quantity of the nucleic acids within the sample.
  • Step 5: Visualization Finally, the sample is examined using fluorescent microscopy. The distinct colors emitted by the fluorophores indicate the presence and location of the target nucleic acids, allowing for detailed analysis of gene expression and genetic organization.

3. Post-Procedure

After the completion of the in situ hybridization (FISH) procedure, careful analysis of the results is conducted. The expected outcomes include the visualization of specific nucleic acid sequences, which can provide valuable information regarding gene presence, copy number, and expression levels. It is essential to document the findings accurately, as these results may influence further diagnostic or therapeutic decisions. Additionally, proper storage and handling of the stained specimens are necessary to preserve the integrity of the results for future reference or additional testing. Follow-up procedures may be required based on the findings, including further genetic testing or clinical evaluations.

Short Descr INSITU HYBRIDIZATION (FISH)
Medium Descr IN SITU HYBRIDIZATION EA MULTIPLEX PROBE STAIN
Long Descr In situ hybridization (eg, FISH), per specimen; each multiplex probe stain procedure
Status Code Active Code
Global Days XXX - Global Concept Does Not Apply
PC/TC Indicator (26, TC) 1 - Diagnostic Tests for Radiology Services
Multiple Procedures (51) 0 - No payment adjustment rules for multiple procedures apply.
Bilateral Surgery (50) 0 - 150% payment adjustment for bilateral procedures does NOT apply.
Physician Supervisions 09 - Concept does not apply.
Assistant Surgeon (80, 82) 0 - Payment restriction for assistants at surgery applies to this procedure...
Co-Surgeons (62) 0 - Co-surgeons not permitted for this procedure.
Team Surgery (66) 0 - Team surgeons not permitted for this procedure.
Diagnostic Imaging Family 99 - Concept Does Not Apply
APC Status Indicator STV-Packaged Codes
Type of Service (TOS) 5 - Diagnostic Laboratory
Berenson-Eggers TOS (BETOS) T1G - Lab tests - other (Medicare fee schedule)
MUE 2

This is a primary code that can be used with these additional add-on codes.

0850T Add On Code Resequenced Code MPFS Status: Carrier Priced APC N Digitization of glass microscope slides for in situ hybridization (eg, FISH), per specimen; each multiplex probe stain procedure (List separately in addition to code for primary procedure)
26 Professional component: certain procedures are a combination of a physician or other qualified health care professional component and a technical component. when the physician or other qualified health care professional component is reported separately, the service may be identified by adding modifier 26 to the usual procedure number.
XU Unusual non-overlapping service, the use of a service that is distinct because it does not overlap usual components of the main service
XS Separate structure, a service that is distinct because it was performed on a separate organ/structure
59 Distinct procedural service: under certain circumstances, it may be necessary to indicate that a procedure or service was distinct or independent from other non-e/m services performed on the same day. modifier 59 is used to identify procedures/services, other than e/m services, that are not normally reported together, but are appropriate under the circumstances. documentation must support a different session, different procedure or surgery, different site or organ system, separate incision/excision, separate lesion, or separate injury (or area of injury in extensive injuries) not ordinarily encountered or performed on the same day by the same individual. however, when another already established modifier is appropriate it should be used rather than modifier 59. only if no more descriptive modifier is available, and the use of modifier 59 best explains the circumstances, should modifier 59 be used. note: modifier 59 should not be appended to an e/m service. to report a separate and distinct e/m service with a non-e/m service performed on the same date, see modifier 25.
76 Repeat procedure or service by same physician or other qualified health care professional: it may be necessary to indicate that a procedure or service was repeated by the same physician or other qualified health care professional subsequent to the original procedure or service. this circumstance may be reported by adding modifier 76 to the repeated procedure or service. note: this modifier should not be appended to an e/m service.
90 Reference (outside) laboratory: when laboratory procedures are performed by a party other than the treating or reporting physician or other qualified health care professional, the procedure may be identified by adding modifier 90 to the usual procedure number.
GC This service has been performed in part by a resident under the direction of a teaching physician
GW Service not related to the hospice patient's terminal condition
Q1 Routine clinical service provided in a clinical research study that is in an approved clinical research study
TC Technical component; under certain circumstances, a charge may be made for the technical component alone; under those circumstances the technical component charge is identified by adding modifier 'tc' to the usual procedure number; technical component charges are institutional charges and not billed separately by physicians; however, portable x-ray suppliers only bill for technical component and should utilize modifier tc; the charge data from portable x-ray suppliers will then be used to build customary and prevailing profiles
XE Separate encounter, a service that is distinct because it occurred during a separate encounter
XP Separate practitioner, a service that is distinct because it was performed by a different practitioner
Date
Action
Notes
2024-01-01 Changed Guideline added.
2015-01-01 Added Added
Code
Description
Code
Description
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