PMC4862217_01
Pedigree. The index patient is indicated by the black arrow
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Fig1
His only brother died at age 48 due to an anaplastic T-cell lymphoma and his daughter died due to a lymphoma at age 30 (Fig. 1).
Multiple lipomas of various sizes on the torso (a), limbs (b) and on the left thumb basal joint right (c)
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Fig2
There were multiple lipomas of various size (the largest measuring approximately 6 x 4 cm), on the torso, limbs and on the basal joint of the left thumb (Fig. 2a-c).
Solid, subcutaneous tumor (2.5 x 2.0 cm in size) at the lower leg
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Fig3
In addition, a solid, subcutaneous tumor (2.5 x 2.0 cm in size) was palpable at the lower leg (Fig. 3).
Preoperative colonoscopic views: tumor of the descending colon (a), polyps of sigmoid colon (b) and rectum (c)
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Fig4
Preoperative gastroscopic view: gastric polypoid lesions
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Fig5
Furthermore, the upper-GI endoscopy revealed more than 60 gastric and about 25 duodenal polypoid lesions (Fig. 5).
PMC4862217_02
Adenocarcinoma of the descending colon (20x) (a) and tubular, low-grade dysplastic tubulo-villous colon adenoma with low grade dysplasia (20x) (b)
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Fig6
Histologic examination of the tumor revealed a moderately differentiated adenocarcinoma arising from a tubular adenoma, which infiltrated the lamina muscularis propria without invasion of the pericolonic adipose tissue (Fig. 6a). Additionally, there were two submucosal lipomas in the ascending colon and five tubular adenomas with low-grade dysplasia (Fig. 6b).
Ganglioneuroma in HE (4x) (a) and S 100 (20x) staining (b)
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Fig7
Immunohistochemical staining for S-100 protein was performed and showed strong reactivity in the spindle cell component, confirming the diagnosis of GP (Fig. 7).
Molecular genetic analyses of PTEN on DNA from blood and tumor tissue from a ganglioneuroma and the colon carcinoma. Next-generation sequencing revealed a stop mutation in PTEN, NM_000314(PTEN):c.138C > A;p.Tyr56* in the patient's blood in a heterozygous state indicated by the allele frequency of about 47.5 % (left). This mutation has not been seen in the first Sanger-Sequencing performed in 2010 (upper left), but was confirmed by a second Sanger-Sequencing in 2014 (lower left, indicated by arrow). The ganglioneuroma (middle) and the colon carcinoma (right) showed the mutation NM_000314:c.138C > A only as a small peak in the first Sanger-Sequencing, but in a heterozygous state in the second Sanger-Sequencing, thus indicating allele drop-out in the first Sequencing. The colon carcinoma additionally showed a second somatic mutation NM_000314(PTEN):c.388C > T;p.Arg130* indicating compound-heterozygous mutation of PTEN in the malignant tumor
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Fig8
The Sanger-Sequencing for PTEN Exon 2 was repeated on DNA from patient's blood, as well as from tissue of the ganglioneuroma and the colon carcinoma and this time the mutation NM_000314:c.138C > A was confirmed in all samples in a heterozygous state (Fig. 8). Re-evaluation of the firstly performed Sanger-sequencing data revealed a small second peak at position c.138 in DNA from the ganglioneuroma and the colon carcinoma, but not from the patient`s blood (Fig. 8).