Molecular identification of metastatic cancer to the skin using laser capture microdissection: a case report.
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.
Milchgrub
S
S
Department of Pathology, The University of Texas Southwestern Medical Center, Dallas, Texas 75235-9073, USA.
Wistuba
I I
II
Kim
B K
BK
Rutherford
C
C
Urban
J
J
Cruz
P D
PD
Gazdar
A F
AF
D000483:Alleles; D002276:Carcinoid Tumor / Q000175:diagnosis* / Q000556:secondary*; D002469:Cell Separation; D004379:Duodenal Neoplasms / Q000473:pathology*; D005260:Female; D005819:Genetic Markers; D006801:Humans; D007834:Lasers; D019656:Loss of Heterozygosity; D008207:Lymphatic Metastasis; D018895:Microsatellite Repeats / Q000235:genetics; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012535:Scalp; D012878:Skin Neoplasms / Q000175:diagnosis* / Q000556:secondary*
D005819:Genetic Markers