Pancreatic Cancer with a Skeletal Muscle Metastasis-A Case Presentation and Literature Review

Abstract

One-half of patients with newly diagnosed pancreatic cancer will have metastatic disease at the time of diagnosis, mainly due to its non-specific initial clinical presentation which includes abdominal pain, dyspepsia, weight loss, bowel habit changes, jaundice and pruritus. The signs, symptoms and stage of the disease at initial diagnosis depends on the origin of the primary tumor, with tumors of the head presenting earlier with obstructive symptoms while tumors of the body/tail are often diagnosed at an advanced stage due to their non-specific presentation. The most common sites of metastasis are the lymph nodes, liver, lung, and peritoneum. The presence of metastatic disease in the skeletal muscles is a rare manifestation of pancreatic cancer and has been described in a limited number of cases. We report the case of a pancreatic cancer patient with a solitary muscle lesion as the only site of extra-nodal metastasis upon initial presentation.

1. Background

Pancreatic cancer is the 11th most commonly diagnosed malignancy in the United States and accounted for an estimated 48,220 deaths in 2021. The aggressive nature and high mortality of the disease are underlined by an average 5-year relative survival rate of 10.8%.1 The most common sites of metastasis are non-regional lymph nodes, liver, lung and peritoneum.2 Skeletal muscle metastases are rarely present in patients with pancreatic cancer.

2. Objective

To report a patient with pancreatic cancer who presented with a rare skeletal muscle metastasis.

3. Case presentation

A 61-year-old Caucasian male with a past medical history of GERD presented to the emergency room with three weeks of left upper quadrant abdominal pain associated with dyspepsia, unintentional weight loss of approximately 30 pounds, and non-specific loose brown bowel movements which were non-watery and not suggestive of steatorrhea. The abdominal pain radiated to his ipsilateral ribcage, back, and left leg; the pain worsened with ambulation and awakened him from his sleep. He denied blood in his stool, nausea, vomiting, fever, chills, night sweats and pruritus. He had a routine screening colonoscopy three years ago without abnormal findings. He was a current smoker (20 pack-years), reported moderate alcohol consumption and a history of recreational cocaine and marijuana use.

On presentation, his vital signs were: blood pressure 140/91 mmHg, heart rate 122/minute, respiratory rate 18/minute, temperature 99.7 °F, and oxygen saturation 99% on room air; he weighed 68 kg and a body mass index of 17.43 kg/m². He was frail-appearing without jaundice or temporal wasting. His abdomen had tenderness and dullness to percussion in the epigastrium and left upper quadrant, without palpable masses; bowel sounds were present. Tenderness was also noted over the left sacroiliac joint, the left paraspinal region and the left rib cage. Straight leg raise test was positive on the left side, while no focal motor or sensory deficits were appreciated. The remainder of the physical examination was unremarkable.

Initial laboratory findings were notable for WBC 11.41 k/uL, hemoglobin 15.7 g/dL, platelets 203 k/uL, total bilirubin 1.8 mg/dL, direct bilirubin 0.8 mg/dL, ALP 175 U/L, AST 45 U/L, ALT 18 U/L, and lipase 40 U/L. A CT of the abdomen and pelvis with contrast revealed: a 9.8 cm × 12.1 cm heterogeneous necrotic left upper quadrant mass (Fig. 1), most likely originating from the pancreas, completely obscuring the pancreatic body and tail and also infiltrating the spleen and the gastric fundal wall; a splenic vein thrombosis was also present; and the pancreatic head was grossly unremarkable. Furthermore, a 5.6 cm × 4.7 cm heterogeneous hypodense left iliac intramuscular mass was found (Fig. 2). The patient was admitted for further work-up of the abdominal mass and was started on anticoagulation for the thrombosis.

Fig. 1.

CT abdomen and pelvis with contrast demonstrating a necrotic 9.8 cm × 12.1 cm left upper quadrant mass which completely obscures the pancreatic body and tail and infiltrates the spleen and gastric fundal wall (arrows). a. Axial Image; b. Coronal Image.

Fig. 2.

CT abdomen and pelvis with contrast demonstrating a heterogeneous hypodense 5.6 cm × 4.7 cm mass within the left iliac muscle (arrows). a. Axial Image; b. Coronal Image.

CT scans of the brain and lumbar spine, and CT angiography of the chest, were negative for any significant pathology. Carcinoembryonic antigen (CEA) and CA 19-9 were 11.3 ng/mL and 159 U/mL, respectively. A subsequent MRI of the abdomen with and without contrast confirmed the presence of the abdominal mass and favored a pancreatic primary. An MRCP revealed no evidence of intrahepatic or extrahepatic biliary dilatation and the pancreatic duct was normal in caliber. MRI of the brain with and without contrast showed no significant abnormal findings. A percutaneous CT-guided core biopsy and aspiration of the left iliac muscle mass was performed. Cytologic examination of the aspirate revealed abundant necrotic debris and sparse significantly atypical cells, suspicious for a neoplastic process. Pathologic examination of the core biopsy specimen demonstrated poorly differentiated carcinoma with necrosis (Fig. 3a). On immunohistochemistry studies the specimen was positive for pancytokeratin (Fig. 3b), Cam 5.2 (Fig. 3c), Vimentin, and CK7; the sample was negative for leukocyte common antigen, HMB45/MART-1, S-100, SOX10, prostate specific antigen, ERG, CK7, CK20, thyroid transcription factor-1, CDX-2, p40, PAX-8, synaptophysin and desmin. The primary site could not be established from histopathologic and immunohistochemistry studies.

Fig. 3.

Pathologic examination of the muscle mass biopsy specimen. a. Hematoxylin and eosin stain (100× magnification): poorly differentiated carcinoma with necrosis; b. Immunohistochemistry stain for Pancytokeratin (100× magnification) positive; c: Immunohistochemistry stain for Cam 5.2 (100× magnification) positive.

The remainder of his hospital course was unremarkable and the patient was discharged with oncology follow-up. An outpatient fluorodeoxyglucose positron emission tomography (F18-FDG PET) scan showed FDG-avid masses in the left abdomen (representing the primary pancreatic tumor) and left gluteal muscles with areas of necrosis as well as enhancing pelvic nodes. He was subsequently referred to radiation oncology for palliative therapy.

4. Discussion

Skeletal muscle metastasis is a rare entity per se, with post-mortem studies reporting a varying incidence of 0.03–17.5%, while the incidence in clinical studies ranges between 0.01 and 0.16%.3–5 From a retrospective review of the literature and the authors’ institutional database, Surov et al reports a cohort of 461 patients with muscle metastases. The most common primary sites of origin for these lesions were lung (25.1%), gastrointestinal (21.0%) and urological tumors (13.2%). This study is in line with two case series of 15 and fewer patients, in which lung and gastrointestinal tumors were more likely to be the primary sites.6,7

Metastatic disease to the skeletal muscles originating from the pancreas has been previously reported. To our knowledge, after an extensive review of the literature, a total of 10 cases have been described since 1894, including cases found either only on autopsy or with clinical involvement of skeletal muscles by the disease.8 These cases include metastasis to the right gluteus maximus muscle,8 metastases to the peroneal muscles in the calf and the anterior compartment muscles in the thigh and shoulder.9 A case of thoracic wall metastasis has been described, with lesions located in the trapezius, teres minor, and infraspinatus muscles10 as well as a rare case of metastasis to the medial masseter and pterygoid muscles.11

As reported in a systematic review of imaging characteristics found in skeletal muscle lesions, among 281 patients with skeletal muscles metastases, the majority presented on CT with intravenous contrast as abscess-like lesions with central low-attenuation and rim-enhancement, followed by homogeneous contrast-enhanced lesions, hypodense lesions (as in our case), and more infrequently isodense.12 Interestingly, between the four studies reviewed in this systematic review that described skeletal muscle metastases as hypodense, two are focused on lesions in the iliopsoas muscle as reported in our case.13,14

The pathophysiologic mechanism of distant metastatic spread in pancreatic cancer is mainly hematogenous, via the arterial or venous route, and through the lymphatic system. The abundant vascular supply of skeletal muscles may account for a possible arterial or venous dissemination and homing of cancer cells to the muscle tissue, although this process is mainly governed by endogenous factors such as the cancer cells’ driver gene mutations as well as transcriptional and posttranscriptional changes. This is depicted by the rare presentation of skeletal muscle metastases in pancreatic cancer. Venous spread, via the portal vein, leads to liver metastases which is the most common presentation of metastatic disease in pancreatic cancer.10,15 Pelvic and abdominal tumors have also been described to spread via the vertebral venous (Batson’s) plexus, which communicates with the inferior vena cava and the mesenterial venous system.4 Lymphatic spread has been considered an early event in tumor development and may be implicated in skeletal muscle metastases, with initial involvement of the sentinel lymph node. Infiltrated lymph nodes may act as a “first stop” for cancer cells preparing to migrate to other organs.15 Perineural invasion has been hypothesized as a possible explanation of muscle metastasis in a patient with bladder cancer; however, in this case, the involved nerves were evident on MRI and PET scans.16

In our case the exact route of dissemination cannot be definitively determined. Histopathologic findings do not include vascular or perineural invasion of the tumor in the microscopic level. Imaging findings (CT scan and PET/CT) do not prove gross invasion of an arterial structure, nerve or direct invasion of the left iliac muscle. The splenic vein thrombosis seen on CT scan may be indicative of likely venous spread of the tumor or may be a result of the hypercoagulable state caused by the cancer itself. The FDG-avid pelvic lymph nodes may be significant for lymphatic spread of the cancer to the skeletal muscle. However, the presence of enlarged and FDG-avid intra-abdominal lymph nodes would be expected on conventional imaging and PET/CT scan indicative of this process. We may hypothesize, given the limitations described above, that the tumor metastasized hematogenously via the venous route or via the lymphatics.

Primary pancreatic tumors most commonly arise from the head of the pancreas (approximately 70%), while differences in clinical presentation and prognosis have been noted between tumors arising from the head and the body/tail of the pancreas. Pancreatic head masses cause obstructive phenomena and manifest early upon the progression of the disease with characteristic signs and symptoms such as nausea, vomiting, jaundice, and abdominal pain. Head/tail tumors are commonly identified at a more advanced stage of the disease and therefore were historically considered to have a worse prognosis.17,18 Notably, a recent retrospective study identified an association between location of the tumor in the body/tail of the pancreas and worse prognosis, irrespective of stages and other prognostic factors, thus concluding that there may be a biologic difference between these two cancer types.18 In our case the primary tumor completely obscured the body and tail of the pancreas while the head appeared unremarkable on conventional imaging. This presentation is in line with the advanced disease stage on diagnosis and the aggressive nature of the disease.

Our patient’s presentation, with only a skeletal muscle metastasis as evidence of extra-nodal metastatic disease, is unique for pancreatic cancer. On histopathology, the skeletal muscle lesion appeared poorly differentiated with marked necrosis, while immunohistochemistry revealed the epithelial component, in line with the radiologic diagnosis of an intra-abdominal malignancy originating from the pancreas. The absence of frank histologic confirmation of pancreatic adenocarcinoma as the primary malignancy in our case is a limitation of this report. Given the aggressive potential of the tumor which drove such an unusual distant spread route, a poorly differentiated phenotype of the metastatic lesion was expected. Nonetheless, the pancreatic origin of the tumor evidenced in CT and MRI as well as the epithelial markers detected in the metastatic site sample allow for a safe interpretation of the disease as adenocarcinoma with the pancreas as the primary site.

5. Conclusion

We report a rare case of a patient diagnosed with pancreatic cancer, with a solitary muscle lesion as the only extra-nodal metastatic site of the disease upon initial presentation. Conventional imaging with CT proved adequate in the characterization of the lesion. Importantly, a highly aggressive malignancy such as pancreatic cancer may present with metastatic lesions to rarely reported sites. Therefore, it is imperative for physicians to familiarize themselves with the various presentations of non-obstructive pancreatic cancer and to investigate any suspicious clinical findings with imaging and further histopathologic workup.