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Molecular identification of metastatic cancer to the skin using laser capture microdissection: a case report
S Milchgrub1, I I Wistuba, B K Kim
1Department of Pathology, The University of Texas Southwestern Medical Center, Dallas, Texas 75235-9073, USA.
Background:
In the current study the authors report a 57-year-old woman with a scalp tumor and cervical lymphadenopathy who had a previously resected duodenal carcinoid. Histologic and immunophenotypic characteristics of the duodenal carcinoid differed from those of the scalp and cervical lymph node tumors, prompting the use of molecular methodologies to make the diagnosis.
Methods:
Paraffin embedded tissues from the duodenal carcinoid, scalp, and lymph node tumors were dissected using microscopic visualization and laser capture microdissection. DNA was extracted and polymerase chain reaction (PCR) was performed to evaluate loss of heterozygosity and microsatellite alterations using primers flanking 22 polymorphic microsatellite markers from 9 chromosomal regions, including genes associated with MEN-1 (11q), CDKN2 (9p), p53 (17p), and bronchial carcinoid (3p). Microdissected lymphocytes from the three tissues were used as source of constitutional DNA (controls).
Results:
Fourteen of the 22 markers were informative (heterozygous in control lymphocytes). A marker on 3p12 showed loss of the same parental allele in the three tumors. A different marker on 3p14.2 showed an identical shifted band in the three tumors indicative of a common microsatellite alteration.
Conclusions:
The shared molecular abnormalities among the three tumors indicated a common clonal origin, leading to a diagnosis of primary duodenal carcinoid with clear cell metastases to the scalp and cervical lymph nodes. These findings led to radiation therapy and immunotherapy rather than chemotherapy. This case illustrates the novel application of laser capture microdissection combined with PCR-based analyses of genomic markers for the identification of the origin of metastatic disease.
Insights
Molecular analysis revealed shared abnormalities in duodenal carcinoid and metastatic tumors. This confirmed a common origin, guiding treatment towards radiation and immunotherapy for metastatic disease.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- A patient presented with a scalp tumor and cervical lymphadenopathy, with a history of a resected duodenal carcinoid.
- Histological and immunophenotypic differences between the duodenal carcinoid and the scalp/lymph node tumors necessitated advanced diagnostic methods.
Observation:
- Laser capture microdissection and PCR-based analysis were used on tumor tissues and constitutional DNA.
- Genomic evaluation focused on loss of heterozygosity and microsatellite alterations at 22 polymorphic markers across 9 chromosomal regions.
Findings:
- Analysis of 22 markers revealed 14 informative markers.
- A shared loss of a parental allele at 3p12 and an identical microsatellite alteration at 3p14.2 were observed in all three tumors.
Implications:
- Shared molecular abnormalities confirmed a common clonal origin for the duodenal carcinoid and its metastases.
- Diagnosis of primary duodenal carcinoid with clear cell metastases to the scalp and cervical lymph nodes was established.
- This led to treatment with radiation therapy and immunotherapy, avoiding chemotherapy, and highlights the utility of molecular techniques in diagnosing metastatic origins.