ANTICANCER RESEARCH 28: 407-414 (2008)

Metastatic Adenocarcinoma in the : Magnetic Resonance Imaging with Pathological Correlations to Mucin Content

SHINYA OSHIRO, HITOSHI TSUGU, FUMINARI KOMATSU, HIROSHI ABE, TADAHIRO OHMURA, SEISABUROU SAKAMOTO and TAKEO FUKUSHIMA

Department of Neurosurgery, Faculty of Medicine, Fukuoka University, Fukuoka, Japan

Abstract. Background: Hypointense signal appearance of may manifest as various signal intensities on routine metastatic adenocarcinoma on T2-weighted imaging (T2-WI) conventional MRI (2, 3). T2-weighted imaging (T2-WI) has been infrequently documented. The purpose of this report commonly shows a cerebral as a hyperintense was to evaluate the degree to which mucin content affects signal mass (4), representing a non-specific finding. The finding of manifestations on conventional MR imaging. Patients and hypointensity is unusual for metastases, but may be more Methods: This series of 24 cases with intracerebral metastatic specific for metastatic adenocarcinoma originating from the adenocarcinoma was assessed retrospectively, focusing on the gastrointestinal (GI) tract (2, 5). This hypointense association between hypointense appearance on T2-WI and appearance on T2-WI could be explained by the mucin intratumoral mucin content. Results: Among the 24 metastatic content found in specimens of metastatic adenocarcinoma adenocarcinomas, intratumoral mucin was histopathologically (3, 6). The purpose of this report was to clarify whether a confirmed in 8 lesions. Of these, 4 masses were demonstrated as characteristic signal appearance is identifiable according to hyperintense signal on T2-WI. The other 4 masses were depicted differences in primary and to evaluate the degree to as isointensity. No cases were identified with hypointense signals which mucin content affects signal manifestations on in mucin-containing metastatic adenocarcinoma. Conversely, conventional MR imaging. only 2 metastatic tumors originating from the stomach exhibited hypointense signal lesions on T2-WI. No histological or Patients and Methods magnetic resonance imaging evidence of blood products or other forms of iron were identified as causes of the hypointense Patient selection. We reviewed the medical records of patients with appearance on T2-WI. Conclusion: This hypointense signal intracerebral metastatic adenocarcinoma who had undergone may simply reflect the relatively shorter T2 relaxation time of surgery at our Institution between January 2002 and December the primary tissue from which metastases arose. Intratumoral 2006. The patient population comprised 24 patients (17 men, 7 women) with a mean age of 56.5 years (range, 38-73 years). mucin itself may be considered to demonstrate the masses as Patients with the following conditions were excluded: previous hyper- or isointense signals in the brain. chemo- or radiotherapy, or biopsy for brain lesions before data acquisition. All study protocols were approved by the institutional Although metastatic brain tumors can usually be diagnosed review board and written informed consent was obtained for MR based on clinical information and imaging studies, some examination. metastatic lesions cannot easily be differentiated from high- grade , malignant or brain abscess on Conventional MRI. All MRI was performed using an Intera Achieva 1.5-T system (Philips Medical Systems, Amsterdam, The conventional magnetic resonance imaging (MRI) (1). The Netherlands). The conventional MRI study included precontrast histology of metastatic brain tumors may affect signal axial T1-WI (repetition time: TR, 600 ms; echo time: TE, 11 ms; intensities. In addition, intratumoral components such as field-of-view, 24x24 cm; matrix, 256 ◊ 224; number of excitation solid tumor, degeneration, hemorrhage or cystic formation pulses, 2; bandwidth, 12.5 kHz; slice thickness, 6 mm; interslice gap, 1 mm; total number of scan slices, 16) and T2-WI (TR, 3500 ms; TE, 85 ms; other parameters were identical to those used in T1-WI) and fluid-attenuated inversion recovery (FLAIR) sequences (TR, Correspondence to: Shinya Oshiro, MD, Department of 9000 ms; TE, 120 ms; time of inversion, 2200 ms; matrix, 256x192; Neurosurgery, Faculty of Medicine, Fukuoka University, 7-45-1 number of excitation pulses, 1; other parameters identical to those Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan. Tel: +81 92 801 used in T1-WI), and contrast-enhanced T1-WI (0.1 mmol/kg of 1011, Fax: +81 92 865 9901, e-mail: [email protected] contrast agent) and FLAIR sequences (double-dose contrast technique) (7). Tumor intensities were classified as hypo-, iso- or Key Words: Adenocarcinoma, metastatic , MRI, mucin. hyperintense to white matter on conventional MRI, and the

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Table I. Summary of 24 cases with metastatic adenocarcinoma.

Case Age/Gender Primary site Lesions Cyst T1-WI T2-WI FLAIR Gd pattern Mucin

1 46/M stomach single – hypo hyper hypo heterogeneous + 2 66/M stomach multiple – iso hypo hypo heterogeneous – 3 71/M stomach multiple – iso hypo hypo homogeneous – 4 53/M stomach multiple + hypo iso iso nodule – 5 47/M duodenum single – hypo hyper iso heterogeneous + 6 55/F colon single – iso iso hypo heterogeneous – 7 72/M colon single – hypo iso hypo homogeneous – 8 49/M colon single – hypo hyper iso heterogeneous – 9 51/F colon single – hypo iso hypo homogeneous – 10 67/F breast single – iso iso iso homogeneous – 11 55/M lung multiple + iso iso iso nodule – 12 61/M lung multiple – hypo hyper iso heterogeneous – 13 46/M lung single – hypo iso iso homogeneous + 14 63/M lung multiple – hypo hyper iso heterogeneous – 15 68/M lung multiple – hypo iso iso heterogeneous – 16 52/F lung multiple + hyper iso hyper ringed + 17 63/M lung single + iso hyper iso ringed + 18 55/M lung single + iso hyper iso nodule – 19 73/F lung multiple – hypo iso hypo heterogeneous – 20 58/M lung single + iso iso iso nodule + 21 43/M lung multiple – hypo iso iso homogeneous – 22 49/M lung single – hypo iso iso heterogeneus – 23 38/F lung multiple + hypo iso iso heterogeneus + 24 54/F lung multiple + hypo hyper hyper nodule + hypo: hypointensity, hyper: hyperintensity, iso: isointensity; Gd pattern: the enhancing portions of tumors are categorized into four contrast enhancement patterns: homogeneous, heterogeneous, nodular and ringed.

enhancing portion of the tumor was analyzed using 4 types of Table II. Correlation between radiological and pathological findings. contrast enhancement pattern: homogeneous (n=6); heterogeneous (n=11); nodular (n=5); and ringed (n=2). Original T1-WI T2-WI FLAIR Pathology lesion Histopathological examination. All 24 surgically obtained specimens Mucin Necrosis Hemorrhage were fixed in 10% formalin and embedded in paraffin. These specimens were stained using hematoxylin and eosin (HE) and Stomach hypo hyper hypo 1+ 1+ 1+ pathological diagnoses were achieved. For the confirmation of Duodenum hypo hyper iso 2+ – – Lung hypo iso iso 1+ – – mucin content, Alcian-blue staining was performed and the Lung hyper iso hyper 1+ 1+ 1+ presence of necrosis or hemosiderin/hemorrhage was carefully Lung iso hyper iso 1+ – – analyzed. Mucin content was evaluated as mild (1+) or moderate Lung iso iso iso 1+ – 1+ (2+), as were the degree of necrosis and hemosiderin/hemorrhage. Lung hypo iso iso 1+ 1+ 2+ Lung hypo hyper hyper 2+ 2+ 1+ Results Mucin content is evaluated as mild (1+) or moderate (2+). Degree of Clinical characteristics. Characteristics of the 24 patients necrosis or hemorrhage/hemosiderin is also graded as mild (1+) or moderate (2+). are included in Table I. Of these, 14 patients had metastatic adenocarcinomas from . Nine patients displayed metastases from GI tract cancer (, n=4; stomach, n=4; duodenal, n=1) Radiological findings. Characteristics of these patients based and 1 patient showed metastasis from on conventional MR findings are also summarized in Table (4.1%). Single metastatic lesions were present in 12 I. On T2-WI, 14 of 24 masses displayed isointense signal patients, with multiple metastases in the other 12 patients. appearance and 8 masses were displayed as hyperintense Sixteen patients exhibited solid component appearance, signals. Only 2 masses originating from stomach cancer while the other 8 patients had masses combined with a displayed a purely hypointense signal appearance (Figure cystic component. 1). On T1-WI, all lesions except for 1 hyperintense signal

408 Oshiro et al: MRI of Intracerebral Metastatic Adenocarcinoma

Figure 1. Case 2. A 66-year-old man with multiple metastases from stomach cancer. Magnetic resonance imaging revealed the heterogeneously enhancing cerebellar mass lesion on contrast-enhanced T1-weighted imaging (A), depicted as signal hypointensity on both T2-weighted (B) and FLAIR imaging (C). A photomicrograph of the tumor specimen (hematoxylin and eosin; original magnification, x100) demonstrated findings compatible with metastatic adenocarcinoma (D).

lesion (Case 16) were demonstrated as hypo- or isointense heterogeneous enhancement patterns, associated with signals. In a post-contrast enhancement study, lesions single metastasis (Figure 2). Conversely, in metastases from demonstrated various enhanced patterns (heterogeneous, lung cancer, 7 out of 14 patients showed a cystic component n=11; homogeneous, n=6; nodule, n=5; ring, n=2). In with nodular or ring enhancement, while 9 patients metastatic lesions originating from colorectal cancer, all 4 exhibited multiplicity of lesions combined with various patients showed solid components with homogeneous or enhancement patterns.

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Figure 2. Case 8. A 49-year-old woman with single metastasis from colon cancer. Magnetic resonance imaging exhibited the irregular enhancing mass on contrast-enhanced T1-weighted imaging (A), represented as signal hyperintensity on T2-weighted imaging (B) and signal isointensity on FLAIR sequence with surrounding edema (C). A photomicrograph of the tumor (hematoxylin and eosin; original magnification, x100) showed the appearance of metastatic adenocarcinoma (D).

Mucin and radiological findings. All 24 specimens stomach and duodenal cancer (Figure 3). On T2-WI, 4 demonstrated findings compatible with metastatic metastatic tumors demonstrated a hyperintense signal adenocarcinoma. Among the lesions, the presence of mucin appearance; the other 4 tumors were seen as isointense was histopathologically confirmed in 8 patients by Alcian- signals. No cases displayed a purely hypointense signal blue stain (Table II). Of these 8 masses, 6 metastatic tumors appearance for metastatic adenocarcinomas. In tissue originated from lung cancer, with 1 tumor each from specimens, some coagulation necroses were observed in 4

410 Oshiro et al: MRI of Intracerebral Metastatic Adenocarcinoma

Figure 3. continued

metastatic adenocarcinomas (stomach, n=1; lung cancer, Discussion n=3), and hemorrhage or hemosiderin deposition was also confirmed to a variable degree in 5 metastatic lesions Hypointensity on T2-WI of metastatic brain tumors, (stomach, n=1; lung , n=4). Our series identified no particularly metastatic adenocarcinoma, has been association between the presence of mucin and the documented in a few reports (8-10). Hinshaw et al. (8) hypointense signal appearance on T2-WI. On the contrary, suggested that this appearance was secondary to magnetic metastatic adenocarcinomas producing mucin tended to susceptibility caused by blood products. Yock (10) and demonstrate areas of hyper- or isointense signal appearance. Egelhoff et al. (3) believed that the appearance might be

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Figure 3. Case 24. A 54-year-old woman with multicystic metastases from lung cancer. Magnetic resonance imaging showed multicystic enhancing mass lesions on contrast-enhanced T1-weighted imaging (A). The solid portion of a left frontal cystic mass is enhanced with a nodular enhancement pattern, which is depicted as hyperintense relative to normal white matter on T2-weighted (B) and FLAIR imaging (C). Photomicrographs of the tumor showed metastatic adenocarcinoma comprising glands of columnar epithelium stained with hematoxylin and eosin (◊200) (D) and mucin stained with Alcian- blue (x250) (E).

attributable to the presence of mucin. Conversely, Carrier et In our series, only 2 metastatic adenocarcinomas from the al. (2) pointed out that this hypointensity might be provoked stomach were shown as purely hypointense signal on T2-WI by shorter T2 relaxation times of extracranial primary tissue scan. These metastases, however, did not show as from which metastases arose. This report evaluated whether hyperintensity on T1-WI, which would have suggested the hypointense signals are related to the presence of mucin or presence of blood products. No significant amounts of blood products in metastatic adenocarcinomas. hemosiderin or other forms of iron were identified in Among the 24 metastatic brain lesions, the presence of specimens following HE staining. No histological or MRI intratumoral mucin was histopathologically confirmed in 8 evidence of blood products or other forms of iron or metastatic lesions. Of these, 6 metastatic tumors originated calcium were noted as the cause of the hypointense from lung cancers, and the other 2 tumors originated from appearance of metastatic adenocarcinoma on T2-WI. The stomach and duodenal cancers. No colorectal cancers were T2 relaxation time of extracranial tissues is generally equal observed. On the other hand, 4 of 8 metastatic lesions to or shorter than that of normal white matter (12, 13), so demonstrated a hyperintense signal appearance on T2-WI. the iso- or hypointense signal appearance of metastatic The other 4 metastatic lesions were depicted as signal adenocarcinoma on T2-WI is simply based on naturally isointensities. No cases showed pure hypointense signals on shorter T2 relaxation times, not on factors such as the T2-WI in mucin-containing metastatic adenocarcinomas. presence of mucin, blood products, iron or calcium. This indicates that the hypointense appearance is not To elucidate points of difference for original lesions of attributable to the presence of mucin. Typically, mucinous brain metastasis as the first manifestation, we investigated and nonmucinous rectal carcinoma can be differentiated tumor multiplicity and complication with cystic components. using preoperative MR imaging, as mucinous carcinoma is In metastatic lesions originating from colorectal cancer, all known to show a characteristic hyperintense signal 4 masses showed a solid component with single metastasis. appearance on T2-WI, and in cases involving other organs, Conversely, in metastasis from lung cancer, roughly one half such as the liver, stomach, breast or pancreas (11). Our of the lesions showed a mixed signal intensity combined findings suggest the possibility of manifestation with hyper- with various components. This corresponded to various or isointense appearance on T2-WI in mucin-containing histological components, such as solid tumor, hemorrhage metastatic brain tumors. and cystic formation, and complications of multiple

412 Oshiro et al: MRI of Intracerebral Metastatic Adenocarcinoma metastases. This study may thus contribute to clarifying the 6 Nakajima H, Adachi J, Nishikawa R and Matsutani M: A differential diagnosis of metastatic adenocarcinoma using metastatic brain tumor showing hypointense on a T2-weighted routine conventional MRI, as regards the origin of the MR imaging: a case report. Jpn J Neurosurg (Tokyo) 11: 695- 698, 2002 (in Japanese). metastatic brain tumor in colorectal and lung cancer. 7 Okubo T, Hayashi N, Shirouzu I, Abe O, Aoki S, Wada A, In conclusion, hypointense signal appearance on T2-WI Ohtomo K and Sasaki Y: Detection of brain metastasis: for intracerebral metastatic adenocarcinoma is likely not comparison of turbo-FLAIR imaging, T2-weighted imaging and attributable to mucin content. This signal appearance may double-dose gadolinium-enhanced MR imaging. Radiat Med simply reflect the relatively shorter T2 relaxation time of the 16: 273-281, 1998. primary tissue from which the metastasis arose. 8 Hinshaw DB and Inouye CT: Metastatic brain . Top Intratumoral mucin itself may be considered to show the Magn Reson Imag 1: 69-78, 1989. 9 Tsuchiya K: MR findings of metastatic brain tumors. Jpn J Clin mass as a hyper- or isointense signal in MRI of the brain. Radiol 34: 1371-1376, 1989 (in Japanese). 10 Yock DH Jr: Magnetic Resonance Imaging of CNS Disease: a References Teaching File. 2 ed. St Lois, Mosby, pp. 1-19, 2002. 11 Hussain SM, Outwater EK and Siegelman ES: Mucinous versus 1 Hayashida Y, Hirai T, Morishita S, Kitajima M, Murakami R, nonmucinous rectal carcinomas: differentiation with MR Korogi Y, Makino K, Nakamura H, Ikushima I, Yamura M, imaging. Radiology 213: 79-85, 1999. Kochi M, Kuratsu J and Yamashita Y: Diffusion-weighted 12 Just M and Thelen M: Tissue characterization with T1, T2 and imaging of metastatic brain tumors: comparison with histologic proton density values: results in 160 patients with brain tumors. type and tumor cellularity. Am J Neuroraodiol 27: 1419-1425, Radiology 169: 779-785, 1988. 2006. 13 Komiyama M, Yagura H, Baba M, Yasui T, Hakuba A, 2 Carrier DA, Mawad ME, Kirkpatrick JB and Schmid MF: Nishimura S and Inoue Y: MR imaging: possibility of tissue Metastatic adenocarcinoma to the brain: MR with pathologic characterization of brain tumors using T1 and T2 values. Am J correlation. Am J Neuroraodiol 15: 155-159, 1994. Neuroradiol 8: 65-70, 1987. 3 Egelhoff JC, Ross JS, Modic MT, Masaryk TJ and Estes M: MR imaging of metastatic GI adenocarcinoma in brain. Am J Neuroroadiol 13: 1221-1224, 1992. 4 Osborn AG: Miscellaneous tumors, cysts, and metastases. Diagnostic Neuroradiology. St Louis, Mosby, pp. 626-670, 1994. 5 Kanai H, Yamada K, Aihara N and Watanabe K: Pineal region metastasis appearing as hypointensity on T2-weighted magnetic Received July 16, 2007 resonance imaging: case report. Neurol Med Chir (Tokyo) 40: Revised October 30, 2007 283-286, 2000. Accepted November 22, 2007

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