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AMP case report: NGS panel aids in diagnosis of rare collision tumor, August 2017

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Jonas J. Heymann, MD; Mahesh M. Mansukhani, MD; Anthony N. Sireci, MD; Hui-Min Yang, MD; Pokala R. Kiran, MD; Antonia R. Sepulveda, MD, PhD

August 2017—CAP TODAY and the Association for Molecular Pathology have teamed up to bring molecular case reports to CAP TODAY readers. AMP members write the reports using clinical cases from their own practices that show molecular testing’s important role in diagnosis, prognosis, and treatment. The following report comes from Columbia University Medical Center. If you would like to submit a case report, please send an email to the AMP at amp@amp.org. For more information about the AMP and all previously published case reports, visit www.amp.org.

Collision tumors are thought to represent the chance encounter and temporospatial interaction of independent tumors, and their accurate classification may have significant prognostic and therapeutic implications. Here we showcase a next-generation sequencing panel used to analyze both components of a potential collision tumor and render the correct diagnosis.

Fig. 1. Ileocolectomy specimen with (A) grossly identifiable fungating mass—outlined in white—extending into pericolic adipose tissue and centrally located firm, white area.

Fig. 1. (A) Ileocolectomy specimen with grossly identifiable fungating mass—outlined in white—extending into pericolic adipose tissue and centrally located firm, white area.

Case presentation and history. The patient was an 87-year-old woman and former smoker who presented with hematochezia and dyspnea on exertion. She denied a history of gynecologic malignancy, uterine fibroids, or vaginal bleeding. Computed tomography of the abdomen and pelvis demonstrated a 6-cm right colonic mass without mesenteric lymphadenopathy. She was found to be severely anemic, with a plasma hemoglobin level of 5.5 g/dL, and to have serum carcinoembryonic antigen level elevated at 46.7 ng/mL. Diagnostic colonoscopy was aborted after the patient developed atrial fibrillation with a rapid ventricular response. Therefore, the patient underwent ileocolectomy.

Fig. 1. (B) Microscopically, an adenocarcinoma interdigitates with a malignant spindle cell proliferation. Photomicrograph was taken at 200× (inset, 400×).

Fig. 1. (B) Microscopically, an adenocarcinoma interdigitates with a malignant spindle cell proliferation. Photomicrograph was taken at 200× (inset, 400×).

Results. Gross examination showed a single 6.6-cm fungating mass extending through the muscularis propria into pericolic adipose tissue. Sectioning revealed an ill-defined firm, white area measuring approximately 3 cm. Histologically, the tumor was a composite of two interdigitating patterns. First, an adenocarcinoma with well-to-moderate differentiation and mucinous features arose from an adenoma with focal high-grade dysplasia. Immunohistochemical analysis demonstrated that adenocarcinoma cells expressed pan-cytokeratin (CK), CK20, and caudal-related homeobox protein-2 (CDX2) but not CK7. Second, the firm, white area identified grossly consisted of a spindle cell proliferation with fascicular architecture, focal necrosis, and high mitotic rate (up to 17 mitoses in 10 high-power fields). IHC analysis demonstrated that malignant spindle cells expressed desmin and smooth muscle actin but not pan-CK, CK7, CK20, CDX2, or markers of gastrointestinal stromal tumor, gynecologic malignancy, and neural and mesothelial origin, suggestive of smooth muscle differentiation. The differential diagnoses included carcinosarcoma and collision of adenocarcinoma and leiomyosarcoma. The carcinoma and sarcoma were staged separately as pT3N0 and pT1bN0, respectively.

IHC analysis also demonstrated loss of expression of MLH1 and PMS2 in the adenocarcinoma component, consistent with a DNA mismatch repair-deficient tumor, whereas expression of all mismatch repair proteins (MLH1, MSH2, MSH6, and PMS2) was preserved in the sarcomatous component. Accordingly, microsatellite instability testing demonstrated high-frequency MSI in the adenocarcinoma but not in the sarcoma.

Mutational analysis was performed separately on the two tumor components by next-generation sequencing with a cancer gene panel. The area of carcinoma demonstrated the following mutations in cancer genes:

  • c.1799T>A missense mutation (NM_004333.4, p.Val600Glu) in the BRAF gene with 22 percent variant allelic fraction;
  • c.451delC frameshift deletion (NM_000546.4, p.Pro151fs) in the TP53 gene with 22 percent allelic fraction;
  • c.3062A>G missense mutation (NM_006218.2, p.Tyr1021Cys) in the PIK3CA gene with 24 percent allelic fraction;
  • c.1624delA frameshift deletion (NM_000368, p.Lys542fs) in the TSC1 gene with 15 percent allelic fraction; and
  • 80 nucleotide variants of uncertain significance.

The sarcomatous component demonstrated a c.2629_2647del frameshift deletion (NM_001042492.2, p.Met877fs) in the NF1 gene with 19 percent allelic fraction, as well as six variants of uncertain significance.

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