Underestimating the Burden of Disease in Sarcomatoid Carcinoma of The Lung: A Case Report and Literature Review

A B S T R A C T

Background: Sarcomatoid carcinomas of the lung (SCL) are rare, aggressive tumors that feature both mesenchymal and epithelial components and are often diagnosed at advanced disease stages. With a poor prognosis for both primary and metastatic SCL, and due to the lack of effective systemic chemotherapy, patients rely heavily on surgery for treatment.
Case Presentation: A 57 year-old man presented with gastrointestinal symptoms, which include anemia and melena, and was originally diagnosed with a gastric ulcer. Subsequent to a PET scan examination, few suspicious lesions were identified in the left upper lung lobe and small bowel, prompting surgical intervention in attempt to alleviate the patient’s gastrointestinal symptoms. The patient underwent a laparoscopic-assisted small bowel resection and intraoperatively, multiple (>10) foci of hyper-pigmented lesions in the small intestine were found, one of which likely being responsible for the events of intussusceptions identified in the patient. Histopathologic and immunohistochemical analyses of the small bowel segments were consistent with the primary lung biopsies, confirming metastatic sarcomatoid of the lung.
Conclusion: This case report illustrates the atypical nature of GI metastases in SCL, warranting physicians to proceed with caution in underestimating the burden of disease when patients diagnosed with SCL present with GI symptoms. Although efforts have produced promising avenues to treatment, more research needs to be conducted to understand sarcomatoid carcinoma of the lung, which has otherwise been difficult to treat due to its rarity, aggressiveness, and occult nature.

Keywords

Pulmonary sarcomatoid carcinoma, sarcomatoid carcinoma of the lung, gastrointesinal metastasis of pulmonary sarcomatoid carcinoma

Background

Sarcomatoid carcinomas of the lung (SCL) are characterized by a malignant mesenchymal component concurrent with a malignant epithelial component [1]. Sarcomatoid carcinomas are rare, aggressive tumors, accounting for less than 1% of all primary pulmonary neoplasms, often diagnosed at advanced disease stages, portending a poor prognosis [1, 2]. It is not unusual for patients to present with synchronous metastases at the time of initial diagnosis. However, reported rates of gastrointestinal metastases are quite rare but should be considered in this patient population.

Case presentation

In 2017, a locally advanced sarcomatoid carcinoma was diagnosed in a 57-year old man (Figure 1). He presented with anemia and melena and was initially diagnosed with a gastric ulcer. The patient had an elevated Prostate Specific Antigen (PSA) and upon further imaging by Positron Emission Tomography (PET) scan, was found to have three lesions: a largely necrotic PET-avid lesion in the left upper lobe of the lung, and two areas of PET avidity in the small bowel (Figure 1).

Subsequently, the patient was taken to the operating room and found to have multiple (>10) foci of hyper-pigmented lesions in the small intestine (Figure 2). One lesion appeared to be responsible for events of intermittent intussusception, which likely contributed to his anemia and the two larger lesions, which likely correlated with the PET scan findings, were excised via segmental bowel resections. However, multiple other lesions observed intraoperatively were not observed on the PET scan and emphasize how the true disease burden was underappreciated preoperatively. To determine if these lesions were metastases, histopathologic analysis identified a markedly pleomorphic dyshesive neoplasm displaying atypical mitotic figures (Figure 3). Furthermore, immunohistochemistry of the small bowel segments were found to be diffusely positive for p63 and focally positive for pancytokeratin OSCAR, pancytokeratin AE1/AE3, and EMA staining, while negative for caudal-related homeobox 2 (CDX2), cytokeratin 20 (CK20) and desmin. These findings in the staining pattern of the lesions were consistent with the primary lung biopsies, confirming metastatic sarcomatoid carcinoma. Following the surgery, the patient recovered well and was subsequently treated with 3850 cGy of palliative external beam radiation over 2 weeks to his left upper lobe lesion followed by seven cycles of carboplatin and paclitaxel and most recently seven cycles of pembrolizumab. The patient is currently alive with disease and his most recent scan demonstrates stable disease for 13 months after bowel resection.

Discussion

This case highlights the occult nature of gastrointestinal metastases in sarcomatoid carcinomas of the lung (SCL). On the PET scan, there were only 2 areas of observed uptake (Figure 1b); however, following diagnostic laparoscopy, greater than 10 deposits of tumor were evident in the small bowel, with diameters that were certainly large enough for PET to detect (Figure 2). Overall, sarcomatoid carcinomas of the lung compose 0.2-0.4% of all primary pulmonary neoplasms [2, 3]. The tumor most often presents as a solitary mass that sits in the upper lobes [4]. SCLs are generally thought to be more aggressive and have a worse prognosis than ordinary lung carcinomas [5, 6]. In a propensity matched model, 63 patients were compared to 62 patients with non-small cell lung cancer (NSCLC) and the 5-year survival for SARC was 24.5% compared to 46.3% in the NSLC group. After resection the median time to recurrence was 11.3 versus 61.4 month [5]. This poor prognosis persists even in Stage I disease, whereby the 5-year survival in SCL was 16.3%, in NSCLC 81.8% and in squamous cell carcinoma was 70.2% [7].

Table 1: Common Sites of Metastases in SCL Patients.

Study (Author/Year)	Age	Male/Female	Metastasis Locations	Symptoms	Imaging Methods	Resection (Y/N)	Subsequent Treatment (Y/N)
Arshad et al., 2017 [33]	63	M	Spine	Back pain, cough	CT scan, MRI	Spine mass removal and laminectomy, no resection of lung mass	Gemcitabine/Carboplatin; biphosphonates for bone metastasis
Takeda et al., 2016 [34]	65	M	Trachea	Hemosputum	CT Scan, bronchoscopy	Unresectable	Carboplatin, paclitaxel plus radiotherapy
Le et al., 2016 [35]	79	M	Upper lip, two intracranial lesions	1 month persistent cough	X-ray, CT scan	Incisional biopsy	Palliative radiotherapy
Romano et al., 2015 [36]	60	M	Intestinal, omental, liver	Chest pain, hemotypsis	CT scan	Small bowel resection	None
de Oliveira et al., 2013 [37]	61	F	Brain	Cough, hemophtysis, fever	CT scan, x-ray, bronchoscopy	Pulmonary lobectomy, microsurgery for resection of brain lesion	None

In this context and due to the lack of effective systemic therapy and the resistance to radiation, surgery is often the preferred modality for primary SCL [8]. Table 1 presents a summary of case reports that have presented a broad spectrum of metastatic locations, with the most common sites of extrapulmonary metastasis being the brain, bone, adrenal glands and liver [9]. The incidence of gastrointestinal metastases is 5-14%, with the small bowel being the most prominent location [4]. Patients who suffer from gastrointestinal metastases in this disease primarily present with melena, abdominal pain, and signs and symptoms of intermittent obstruction in the context of intussusception [9]. However, SCL patients who suffer from small bowel metastasis particularly may present asymptomatically, with the progression later being revealed through perforation, obstruction, or gastrointestinal bleeding [10]. Incidences of secondary metastasis, especially those that present at later stages due to the lack of initial symptoms, require surgical intervention in almost every case as intestinal intussusception is known to cause bowel obstruction, intestinal necrosis, and bleeding [11]. As demonstrated in this case report, the nature of these metastatic deposits can be often difficult to detect and therefore in the context of symptoms, there should be a particularly low threshold of concern for further imaging or workup. Imaging to detect metastases is most commonly in the form of PET scans or CT scans, however as demonstrated in this case, the burden of disease can be underestimated. In patients with primary carcinoma of the lung with gastrointestinal metastases, McNeill et al have reported an average of 4.8 metastatic sites, which can allow for a substantial underestimation if the burden of disease is not fully appreciated through cross sectional modalities [12].

SCL most often presents with a biphasic histology, concerning both epithelial and mesenchymal characteristics. The biphasic characteristics are comprised of a component of NSCLC that is intermingled with a sarcomatoid component (formerly pleomorphic carcinoma) or with heterologous sarcomatous tissue (formerly described as carcinosarcoma) [7]. Under the umbrella of sarcomatoid carcinoma of the lung, pathological characteristics have further characterized various subtypes of the disease, which are pleomorphic carcinoma, spindle cell carcinoma, giant cell carcinoma, carcinosarcoma, and pulmonary blastoma [13-15]. Staining characteristics of this disease include CK7+ consistent with an epithelial component, and vimentin, signifying mesenchymal differentiation [16]. Tumors can also be positive for TTF-1, alluding to their pulmonary origin [4].

In early stage operable SCL patients, surgical intervention remains the standard of care among candidates and has proven to produce the greatest overall survival benefit [17, 18]. In a retrospective study at the University of Cincinnati Medical Center (UCMC), Karim et al. demonstrated an overall survival of 713.5 days, or 23.5 months in patients that underwent surgery, a sentiment that has been widely consistent with various other institutional studies conducted [17]. Furthermore, the aforementioned study explored overall survival of SCL patients when chemotherapy treatment was accounted for as the study stated that patients who underwent systemic chemotherapy and surgery had an overall survival of 457.5 days, or 15 months, whereas those who underwent chemotherapy only had an overall survival of only 256 days, or 8.4 months [17].

Table 2: Summary of Cross-Sectional Studies on SCL Patients.

Study (Author, Year)	No. of Patients	AJCC Staging	5-year Survival	Recurrence Rate (%)	Recurrence	Median Survival (months)	Resection (Y/N, %)	Chemotherapy (Y/N, %)
Weissferdt et al., 2017 [38]	86	IA: 5 patients (5.8%) IB: 9 patients (10.5%) IIA: 12 patients (14.0%) IIB: 32 patients (37.2%) IIIA: 22 patients (25.6%) IIIB: 3 patients (3.5%) IV: 2 patients (2.3%) NK 1 patient (1.2%)	34.60%	NR	NR	15	Yes, 100%	Yes, 27% neoadjuvant, 60% adjuvant
Roesel et al., 2017 [39]	58	IA: 4 patients (8.7%), IB: 7 patients (15.2%), IIA: 9 patients (19.6%), IIB:15 patients (32.6%), III: 7 patients (15.2%) IV: 4 patients (8.7%)	28.70%	60.90%	Local: 8 patients Distant:12 patients Both: 8 patients	Stage I: 44.9 Stage II: 14.9 Stage III: 10.2 Stage IV: 5.6	Yes, 79.3%	Yes, 31%
Steuer et al., 2017 [40]	7965	I: patients (18%), II: patients (10%), III: patients (24%), IV: patients (48%)	14.40%	NR	NR	6.4	Yes, 38%	Yes, 39%
Lococo et al., 2016 [41]	148	I: 36 patients (24%) II: 69 patients (47%) III: 33 patients (22%) IV: 10 patients (7%)	12.6%	70%	Local: 58% of cases Distant: 81% of cases	19	Yes, 100%	Yes, 67%
Gu et al., 2015 [42]	95	I: patients (24.2%) II: patients (27.4%) III: patients (31.6%) IV: patients (16.8%)	21%	NR	NR	11.54	Yes, 92.6%	Yes, 37.9%
Mochizuki et al., 2008 [43]	70	I: 23 patients (33%) II: 22 patients (31%) III: 20 patients (29%) IV: 5 patients (7%)	36.7%	58.5%	Local: 29% of cases Bone: 29% of cases Brain: 25% of cases Pleura: 17% of cases Liver: 17% of cases Thorax and Neck Lymph Nodes: 8% of cases Adrenal glands: 8% of cases Stomach: 4% of cases Jejunum: 4% of cases Skin: 4% of cases	23	Yes, 100%	NR
Martin et al., 2007 [5]	63	IA: patients (8%) IB: patients (19%) IIA: patients (0%) IIB: patients (30%) IIIA: patients (22%) IIIB: patients (16%) IV: patients (5%)	24.5%	62.5%	Local: 21% of cases Distant: 51% of cases	17.4	Yes, 100%	Yes, 24% pre-operative chemo
Venissac et al., 2007 [44]	39	IB:15 patients (38.5%) IIB:14 patients (35.9%) IIIA: 7 patients (17.9%) IIIB: 2 patients (5.1%) IV: 1 patient (2.6%)	33%	53.8%	Local: 10 cases Brain: 9 cases Bone: 6 cases Lung: 4 cases Bowel: 2 cases Suprarenal Gland: 1 case	11	Yes, 100%	Yes, 43.6%

Despite surgery being the preferred treatment option for SCL patients with early localized disease, high recurrence rates have unfortunately been reported [19]. Recent cross-sectional studies at various institutions have reported recurrence rates greater than 50% in SCL patients who have undergone surgical intervention, with rates ranging from 53.8% to 70% (Table 2). As seen in this case report, the high incidence rate of recurrence may be attributed to the highly aggressive, occult nature of SCL and the underestimation of the burden of disease through cross sectional imaging. Furthermore, the underappreciation of the burden of disease is accentuated by the fact that the majority of recurrences in SCL surgical patients are distant, rather than local (Table 2). Lococo et al. have reported a distant recurrence rate of 81% in 148 consecutive patients across five institutions, even in 62% of patients who possessed pathological stage I tumors and underwent R0 resections [20]. The underappreciation of SCL may have been a contributing factor to hidden metastatic deposits, which unfortunately led to worse prognostic outcome in surgical patients that had been deemed no evidence of disease (NED) after pathological confirmation.

In spite of the potential for recurrent disease in surgical candidates with sarcomatoid carcinoma of the lung, surgical excision remains the preeminent treatment option as current lines of chemotherapy are ineffective and there are not targeted immunotherapeutic drugs or cancer vaccines for SCL, due to the rarity of the disease [19, 21]. In a cohort study of 56 SCL patients who underwent an R0 lung cancer resection, Chaft et al. demonstrated that there was not a significant difference in disease free probability (DFP) of SCL patients that were deemed stage Ib-IIa; however, there was a benefit seen in patients with IIb-IIIa disease [22]. Vieira et al. further explored the efficacy of first-line chemotherapy in a study with 97 SCL patients that possessed advanced or metastatic disease and showed that there was not a statistical difference between the overall survival of patients receiving or not receiving a platinum-based chemotherapy [23]. Thus, there remains an equivocal response seen in SCL patients at various cancer stages and a need to comprehensively understand the carcinogenesis of the SCL.

Due to the rarity of this tumor type, the genetic and molecular characterization of SCL remains to be further elucidated. Recent research efforts, however, have shed light on potential sources of genetic alteration in SCL patients which may be conducive to engineering new cancer drugs. Table 3 summarizes various genetic profiling studies in literature that have identified genetic markers in SCL patients (Table 3). Next generation sequencing analysis of a panel of 26 genes was performed on 49 surgical specimens and has evaluated the prognostic impact and survival implications of the genetic profiles. The findings demonstrated that mutations in KRAS alone or in combination with the tumor protein p53 gene were associated with a decreased survival probability and a higher local and distant recurrence rate [7]. Along the same lines, Mehrad et al. concluded that KRAS mutation is predictive of outcome in SCL patients and is associated significantly with poor survival [24].

Table 3: Common Genetic Markers Associated with SCL.

Study (Author, Year)	No. of Patients	% of Patients with Mutations
Schrock et al., 2017 [45]	125	TP53: 74%, KRAS, 34%, MET: 13.6%, EGFR: 8.8%, BRAF: 7.2%, HER2: 1.6%, RET: 0.8%
Li et al., 2017 [46]	7	TP53: 57.1%, MET: 14.1%, APC: 14.1%, HGF: 14.1%, PIK3CA: 14.1%, EGFR: 14.1%, BRAF: 14.1%
Lococo et al., 2016 [7]	49	TP53: 55%, KRAS: 39%, PIK3CA: 12%, STK11: 8%, APC: 6%, PTEN: 6%, BRAF: 2%. EGFR: 2%
Fallet et al., 2015 [47]	81	KRAS: 27.2%, EGFR: 22.2%, TP53: 22.2%, STK11: 7.4%, NOTCH1: 4.9%, NRAS: 4.9%, PI3KCA: 4.9%
Kaira et al., 2015 [48]	17	EGFR: 18%
Cancer Genome Atlas Research Network, 2014 [49]	230	TP53: 46%, KRAS: 33%, STK11: 17%, BRAF: 10%, PIK3CA: 7%, MET: 7%
Chang et al., 2011 [27]	42	TP53: 28.6%, EGFR: 23.8%
Italiano et al., 2009 [50]	22	KRAS: 38%, EGFR: 0%

Not only do these studies help implicate prognosis of SCL patients, but also convey information that aids in the potential creation of gene regulation drugs. EGFR tyrosine kinase inhibitors, which are commonly used to treat head and neck and lung cancers, have been show to induce a response in approximately 70% of NSCLCs with EGFR mutations [25-27]. However, as seen by the genetic profiling studies, only a small percentage of SCL patients possess the EGFR mutation.

Recent studies have alluded to a potential biomarker-driven target approach for SCL patients in the inhibition of MET-driven oncogenic pathways [24, 28, 29]. The specific alteration of the pathway features a mutation in which exon 14 of the MET gene is spliced. Liu et al. reports 8 (22%) cases of MET mutations leading to exon 14 skipping [28]. In the same study, dramatic response to crizotinib, a small-molecule kinase inhibitor for MET, was seen in a patient with chemotherapy-refractory disease possessing a MET exon 14 skipping mutation [28, 30].

Programmed death-ligand 1 (PD-L1) also provides a promising avenue of immunotherapeutic treatment in SCL patients. In 2013, Velcheti et al. demonstrated a high level of expression of PD-L1 in this disease, approximating 69% of SCL patients that were positive for PD-L1, which is higher than conventional expression in NSCLC patients [31]. Thus, the results from Velcheti et al. provide a rationale for increased emphasis of PD-L1 as a potential immunotherapeutic target. Despite its potential in creating new targeted immunotherapeutic drugs, higher levels of PD-L1 have also been shown to be a worse prognostic factor in SCL patients [32]. However, in light of its correlation to a poorer prognosis, PD-L1 remains to be a target in creating novel immunotherapy strategies in a disease that has otherwise been difficult to treat due to its rarity, aggressiveness, and occult nature.

Conclusion

This case illustrates the atypical nature of GI metastases in SCL, warranting physicians to proceed with caution in underestimating the burden of disease when patients diagnosed with SCL present with GI symptoms. In addition to gastrointestinal deposits, it has been reported in literature the copious amount of locations that SCL may metastasize to, ranging from the spine to upper lip. Because of a lack of response to chemotherapy, understanding the true burden of disease in SCL should be further emphasized as surgical intervention remains the standard of care. Although efforts have produced promising avenues to treatment, more research needs to be conducted to understand sarcomatoid carcinoma of the lung, which has otherwise been difficult to treat due to its rarity, aggressiveness, and occult nature.

Funding

Work reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under award number NIH 5K12CA001727-20. The content is solely the responsibility of Laleh Melstrom and does not necessarily represent the official views of the National Institutes of Health.

Disclosures

None.

Article Info

Article Type

Case Report & Literature Review

Publication history

Received: Fri 20, Sep 2019
Accepted: Thu 10, Oct 2019
Published: Tue 12, Nov 2019

Copyright

© 2023 Laleh Melstrom. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Hosting by Science Repository.
DOI: 10.31487/j.GSCR.2019.01.03

Author Info

Indra M. Newman Jae Kim Laleh Melstrom Massimo D’Apuzzo Paul Wong

Corresponding Author

Laleh Melstrom
Department of Surgery, City of Hope National Medical Center

Figures & Tables

Table 1: Common Sites of Metastases in SCL Patients.

Study (Author/Year)	Age	Male/Female	Metastasis Locations	Symptoms	Imaging Methods	Resection (Y/N)	Subsequent Treatment (Y/N)
Arshad et al., 2017 [33]	63	M	Spine	Back pain, cough	CT scan, MRI	Spine mass removal and laminectomy, no resection of lung mass	Gemcitabine/Carboplatin; biphosphonates for bone metastasis
Takeda et al., 2016 [34]	65	M	Trachea	Hemosputum	CT Scan, bronchoscopy	Unresectable	Carboplatin, paclitaxel plus radiotherapy
Le et al., 2016 [35]	79	M	Upper lip, two intracranial lesions	1 month persistent cough	X-ray, CT scan	Incisional biopsy	Palliative radiotherapy
Romano et al., 2015 [36]	60	M	Intestinal, omental, liver	Chest pain, hemotypsis	CT scan	Small bowel resection	None
de Oliveira et al., 2013 [37]	61	F	Brain	Cough, hemophtysis, fever	CT scan, x-ray, bronchoscopy	Pulmonary lobectomy, microsurgery for resection of brain lesion	None

Table 2: Summary of Cross-Sectional Studies on SCL Patients.

Study (Author, Year)	No. of Patients	AJCC Staging	5-year Survival	Recurrence Rate (%)	Recurrence	Median Survival (months)	Resection (Y/N, %)	Chemotherapy (Y/N, %)
Weissferdt et al., 2017 [38]	86	IA: 5 patients (5.8%) IB: 9 patients (10.5%) IIA: 12 patients (14.0%) IIB: 32 patients (37.2%) IIIA: 22 patients (25.6%) IIIB: 3 patients (3.5%) IV: 2 patients (2.3%) NK 1 patient (1.2%)	34.60%	NR	NR	15	Yes, 100%	Yes, 27% neoadjuvant, 60% adjuvant
Roesel et al., 2017 [39]	58	IA: 4 patients (8.7%), IB: 7 patients (15.2%), IIA: 9 patients (19.6%), IIB:15 patients (32.6%), III: 7 patients (15.2%) IV: 4 patients (8.7%)	28.70%	60.90%	Local: 8 patients Distant:12 patients Both: 8 patients	Stage I: 44.9 Stage II: 14.9 Stage III: 10.2 Stage IV: 5.6	Yes, 79.3%	Yes, 31%
Steuer et al., 2017 [40]	7965	I: patients (18%), II: patients (10%), III: patients (24%), IV: patients (48%)	14.40%	NR	NR	6.4	Yes, 38%	Yes, 39%
Lococo et al., 2016 [41]	148	I: 36 patients (24%) II: 69 patients (47%) III: 33 patients (22%) IV: 10 patients (7%)	12.6%	70%	Local: 58% of cases Distant: 81% of cases	19	Yes, 100%	Yes, 67%
Gu et al., 2015 [42]	95	I: patients (24.2%) II: patients (27.4%) III: patients (31.6%) IV: patients (16.8%)	21%	NR	NR	11.54	Yes, 92.6%	Yes, 37.9%
Mochizuki et al., 2008 [43]	70	I: 23 patients (33%) II: 22 patients (31%) III: 20 patients (29%) IV: 5 patients (7%)	36.7%	58.5%	Local: 29% of cases Bone: 29% of cases Brain: 25% of cases Pleura: 17% of cases Liver: 17% of cases Thorax and Neck Lymph Nodes: 8% of cases Adrenal glands: 8% of cases Stomach: 4% of cases Jejunum: 4% of cases Skin: 4% of cases	23	Yes, 100%	NR
Martin et al., 2007 [5]	63	IA: patients (8%) IB: patients (19%) IIA: patients (0%) IIB: patients (30%) IIIA: patients (22%) IIIB: patients (16%) IV: patients (5%)	24.5%	62.5%	Local: 21% of cases Distant: 51% of cases	17.4	Yes, 100%	Yes, 24% pre-operative chemo
Venissac et al., 2007 [44]	39	IB:15 patients (38.5%) IIB:14 patients (35.9%) IIIA: 7 patients (17.9%) IIIB: 2 patients (5.1%) IV: 1 patient (2.6%)	33%	53.8%	Local: 10 cases Brain: 9 cases Bone: 6 cases Lung: 4 cases Bowel: 2 cases Suprarenal Gland: 1 case	11	Yes, 100%	Yes, 43.6%

Table 3: Common Genetic Markers Associated with SCL.

Study (Author, Year)	No. of Patients	% of Patients with Mutations
Schrock et al., 2017 [45]	125	TP53: 74%, KRAS, 34%, MET: 13.6%, EGFR: 8.8%, BRAF: 7.2%, HER2: 1.6%, RET: 0.8%
Li et al., 2017 [46]	7	TP53: 57.1%, MET: 14.1%, APC: 14.1%, HGF: 14.1%, PIK3CA: 14.1%, EGFR: 14.1%, BRAF: 14.1%
Lococo et al., 2016 [7]	49	TP53: 55%, KRAS: 39%, PIK3CA: 12%, STK11: 8%, APC: 6%, PTEN: 6%, BRAF: 2%. EGFR: 2%
Fallet et al., 2015 [47]	81	KRAS: 27.2%, EGFR: 22.2%, TP53: 22.2%, STK11: 7.4%, NOTCH1: 4.9%, NRAS: 4.9%, PI3KCA: 4.9%
Kaira et al., 2015 [48]	17	EGFR: 18%
Cancer Genome Atlas Research Network, 2014 [49]	230	TP53: 46%, KRAS: 33%, STK11: 17%, BRAF: 10%, PIK3CA: 7%, MET: 7%
Chang et al., 2011 [27]	42	TP53: 28.6%, EGFR: 23.8%
Italiano et al., 2009 [50]	22	KRAS: 38%, EGFR: 0%

Figure 1: PET scan demonstrating PET avidity of nodules in the abdomen on coronal (a) and axial (b) slices.

Figure 2: Laparoscopic findings of surgery demonstrating pigmented nodules on multiple areas of small bowel (a) and resection specimen where hemorrhoage had occurred (b).

Figure 3: H&E slide of tumor specimen.

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