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CASE REPORT
Ahead of print publication  

Gastric signet ring cell carcinoma presenting with widespread osteoblastic metastases


1 Department of Radiology, Ondokuz Mayis University, Faculty of Medicine, Samsun, Turkey
2 Department of Radiation Oncology, Samsun Education and Research Hospital, Samsun, Turkey
3 Department of Pathology, Ondokuz Mayis University, Faculty of Medicine, Samsun, Turkey

Date of Submission06-Dec-2018
Date of Decision15-Apr-2019
Date of Acceptance15-May-2019
Date of Web Publication30-Jan-2020

Correspondence Address:
Ayşegül İdil Soylu,
Department of Radiology, Faculty of Medicine, Ondokuz Mayis University, 55139 Samsun
Turkey
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jcrt.JCRT_834_18

 > Abstract 


Gastric cancer infrequently metastasizes to the bone. These metastases are generally osteolytic. On the other hand, osteoblastic metastases are very rare. In this case report, a patient with signet ring cell gastric carcinoma presenting with diffuse osteoblastic bone metastases who had no laboratory abnormalities at the time of diagnosis is described. To our knowledge, our patient represents the longest surviving case compared with the similar cases in literature.

Keywords: Gastric carcinoma, osteoblastic metastasis, signet ring cell



How to cite this URL:
Soylu A&, Odabaşı E, Gün S, Selçuk MB. Gastric signet ring cell carcinoma presenting with widespread osteoblastic metastases. J Can Res Ther [Epub ahead of print] [cited 2020 Feb 29]. Available from: http://www.cancerjournal.net/preprintarticle.asp?id=277362




 > Introduction Top


Many advanced-stage malignancies cause bone metastases. Metastases are mostly osteolytic and rarely osteoblastic. A variety of mediators released from tumor cells activate osteoclasts and osteoblasts, leading to the formation of bone lesions.[1] Although prostate cancer is the first leading cause of osteoblastic metastases, lung, pancreatic, breast, colon, thyroid, and urinary bladder cancers may also cause osteoblastic metastases.[2] Rare cases with osteoblastic metastases accompanying gastric cancer are also reported in literature.[3],[4],[5]

In this case report, we present a case followed for osteoblastic bone metastases for a long time before he had the primary diagnosis of signet ring cell gastric carcinoma.


 > Case Report Top


A 74-year old male patient was referred to our hospital with dyspeptic complaints. He had no abnormal findings in his physical examination. Complete blood count and routine biochemistry results were normal, except for elevated alkaline phosphatase (ALP) (910 IU/L). Parathyroid hormone (PTH) was borderline high (74.1 pg/mL). Free triiodothyronine (fT3), free thyroxine (fT4), thyroid-stimulating hormone (TSH), prostate-specific antigen (PSA), free PSA, Ca, 19-9 and carcinoembryonic antigen were normal. Alpha-fetoprotein was negative. Gastroscopy showed a suspicious malignant lesion completely encircling the lumen in prepyloric antrum without pyloric involvement. Colonoscopy revealed no pathology other than Grade 2–3 external hemorrhoids. A contrast-enhanced thoracic and abdominopelvic computed tomography demonstrated wall thickening of the gastric antrum completely encircling and narrowing the gastric lumen, minimal stranding in the surrounding fat tissue and diffuse density areas in all bony structures within the image area [Figure 1]. There was no lymphadenopathy or solid organ metastasis. Furthermore, there was no increased uptake in the technetium 99m bone scintigraphy. A tru-cut biopsy of the pelvis was performed to rule out metastasis.
Figure 1: A contrast-enhanced abdominal computed tomography demonstrated wall thickening of the gastric antrum completely encircling and narrowing the gastric lumen (arrow) (a). Coronal (b) and Sagittal (c) thoracoabdominal computed tomography imaging demonstrated diffuse sclerotic bone lesions

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Histopathology of the gastric biopsy indicated signet ring cell gastric carcinoma, and signet ring cells were also found in the bone biopsy samples. In the immunohistochemical study, the cells were positive with pancytokeratin (Clone AE1/AE3, Thermo Scientific) and negative with PSA (Clone 140, Genemed) and Napsin A (Clone TMU-Ad2, Biocare) [Figure 2]. In the light of these findings, oncological medical therapy was initiated for our case of signet ring cell gastric carcinoma presenting with bone metastases. Six months after neoadjuvant chemotherapy, subtotal gastrectomy and lymph node dissection were performed. Histopathological examination of the surgical specimen also showed the presence of signet ring cell gastric carcinoma. Of the 16 lymph nodes, 10 had metastatic signet ring cells.
Figure 2: Signet ring cells are seen in the bone biopsy samples (H and E, ×200) (a), (pancytokeratin antibody-DAB, ×100) (b)

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The patient's history showed that he referred to a hospital due to low back pain 1.5 years ago. His physical examination was normal. Furthermore, magnetic resonance imaging and bone X-ray screening were performed at the time of his first admission to the hospital. They showed sclerotic lesions in his lumbar vertebrae and pelvic bones [Figure 3]. Routine laboratory parameters such as blood calcium, ALP, PTH, PSA, and Ca 19-9 were normal, and the results of99m Tc bone scintigraphy were suggestive of Paget's disease. His breast examination and prostate biopsy were normal as well as his gastroscopy and colonoscopy. It was decided to follow-up the patient closely because laboratory parameters such as calcium, PTH, and ALP were normal and the bone lesions were inconsistent with any metastatic or metabolic bone disorders. Furthermore, there was no primary malignancy that could be associated with bone metastases.
Figure 3:Diffuse sclerotic metastatic lesions in vertebrae (a) and pelvic bones (b) are seen bone X-ray screening

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During his follow-up, a99m Tc bone scintigraphy showed accumulation of heterogeneous tracer uptake bilaterally in the ribs, thoracic vertebrae, and the sternum. It was considered as degenerative inflammatory changes. Breast and abdominal ultrasound examination were normal. His ALP level was elevated (500 IU/L). A subtype analysis for ALP showed osseous origin, and other laboratory parameters were in the normal range.

He had no history of alcohol use or smoking. Furthermore, he had no bone pain during follow-up except lower back pain when he referred to a hospital for the first time 1.5 years ago.


 > Discussion Top


Osteoblastic metastases most prominently occur in prostate cancer. Other malignancies such as lung, pancreas, breast, colon, thyroid, and urinary bladder cancer rarely lead to osteoblastic metastases. Infiltrative blood disorders such as lymphoma or leukemia, fluorosis, renal dystrophy, or metabolic conditions such as Paget's disease can cause sclerotic bone lesions.[2],[6] Other clinical and laboratory findings of the condition associated with the bone lesions may be helpful for differential diagnosis. In our case, gastroscopy and laboratory tests performed for the diagnosis of primary malignancy revealed no specific result at his first admission to the hospital. Although there was no specific diagnosis, it was thought to be inconsistent with malignancy. Hence, it was decided to follow-up the patient closely.

Gastric cancers are generally diagnosed at an advanced stage with distant organ metastases. The reported frequency of bone metastasis in gastric cancer patients is 2% to 20%. Many cases also have concomitant liver or lung metastases.[7] In early-stage gastric cancer characterized by only mucosal or submucosal involvement, the hematogenous metastasis incidence is <1%.[8],[9] Kato et al. reported six cases of early gastric cancer with distant metastases, and all were found to have signet ring cell carcinoma.[10]

Metastases associated with gastric carcinoma are frequently osteolytic and osteoblastic metastases are unlikely.[2] To our knowledge, until now, only 12 cases of osteoblastic bone metastases associated with signet ring cell gastric carcinoma have been reported in the literature. Except for a single case, bone metastases were identified simultaneously with gastric carcinoma. Furthermore, patients had elevated ALP and tumor markers at the time of the diagnosis. On the other hand, Anagnostopoulos et al.[4] reported a patient with early-stage gastric cancer who had mucosal involvement. The patient had normal ALP and tumor markers, but he had osteoblastic bone metastases 3 weeks after gastrectomy. The authors underlined the importance of the fact that cancer may be associated with bone metastases even at early stages.

Our patient represents the first case with osteoblastic bone metastases who had no detectable primary tumor for a long time. The longest duration of time reported for such patients in the literature is 3 weeks. To our knowledge, he also represents the longest surviving signet ring cell gastric carcinoma patient. Similar to the patient reported by Anagnostopoulos et al.,[4] our patient also has normal ALP and tumor markers. In other reported gastric carcinoma patients with synchronous osteoblastic bone metastases, ALP and tumor markers are elevated at the time of diagnosis. Despite the detection of bone metastasis, the delay in the diagnosis of our patient is associated with the absence of lesion in gastroscopy and colonoscopy, no laboratory findings suggestive of malignancy and the silent clinical course.


 > Conclusion Top


Diffuse sclerotic bone metastases may be the only sign in patients with early-stage signet ring cell gastric carcinoma. Despite bone metastases, tumor markers may not be elevated during the early stages of cancer. A gradual increase in ALP level may be the only detectable finding. In patients with sclerotic bone lesions of unknown etiology, it should be kept in mind that gastroscopy and bone biopsy may allow an early diagnosis.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
 > References Top

1.
Guise TA, Mohammad KS, Clines G, Stebbins EG, Wong DH, Higgins LS, et al. Basic mechanisms responsible for osteolytic and osteoblastic bone metastases. Clin Cancer Res 2006;12:6213s-6s.  Back to cited text no. 1
    
2.
Resnick D, Niwayama G. editors. Skeletal metastasis. In: Diagnosis of Bone and Joint Disorders. Vol. 6. 2nd ed. Philadelphia: Saunders; 1988. p. 3945-4010.  Back to cited text no. 2
    
3.
Ermiş F, Erkan ME, Besir FH, Oktay M, Kutlucan A, Aydın Y. Osteoblastic metastasis from signet ring cell gastric cancer in a young male. Turk J Gastroenterol 2014;25 Suppl 1:284-6.  Back to cited text no. 3
    
4.
Anagnostopoulos G, Sakorafas GH, Kostopoulos P, Margantinis G, Tsiakos S, Pavlakis G. Early (mucosal) gastric cancer with synchronous osteosclerotic bone metastases: A case report. Eur J Cancer Care (Engl) 2010;19:554-7.  Back to cited text no. 4
    
5.
Link Y, Romano A, Bejar J, Schiff E, Dotan Y. Widespread osteoblastic metastases and marked elevation of CA19-9 as a presentation of signet ring cell gastric carcinoma. J Gastrointest Oncol 2016;7:E1-5.  Back to cited text no. 5
    
6.
Carstens SA, Resnick D. Diffuse sclerotic skeletal metastases as an initial feature of gastric carcinoma. Arch Intern Med 1980;140:1666-8.  Back to cited text no. 6
    
7.
Yoshikawa K, Kitaoka H. Bone metastasis of gastric cancer. Jpn J Surg 1983;13:173-6.  Back to cited text no. 7
    
8.
Baba H, Maehara Y, Okuyama T, Orita H, Anai H, Akazawa K, et al. Lymph node metastasis and macroscopic features in early gastric cancer. Hepatogastroenterology 1994;41:380-3.  Back to cited text no. 8
    
9.
Lawrence M, Roselli A. Early gastric carcinoma. Twenty-eight years experience. Ann Surg 1991;85:171-6.  Back to cited text no. 9
    
10.
Kato Y, Inoshita N, Yanagishawa A, Ota K, Nakajima T. Clinicopathological features of gastric carcinoma in stage IV (in Japanese). Gastroenterol Surg 1997;20:1333-6.  Back to cited text no. 10
    


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  [Figure 1], [Figure 2], [Figure 3]



 

 
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