Ann Thorac Surg 2005;79:e1-e2
© 2005 The Society of Thoracic Surgeons
Case report
Multiple Ground-Glass Opacity in Metastasis of Malignant Melanoma Diagnosed by Lung Biopsy
Riki Okita, MDa,*,
Motohiro Yamashita, MDa,
Masao Nakata, MDa,
Norihiro Teramoto, MDb,
Akihiro Bessho, MDc,
Hiroshi Mogami, MDd
a Department of Surgery, National Shikoku Cancer Center Hospital, Matsuyama, Japan
b Department of Pathology, National Shikoku Cancer Center Hospital, Matsuyama, Japan
c Department of Internal Medicine, National Shikoku Cancer Center Hospital, Matsuyama, Japan
d Department of Radiology, National Shikoku Cancer Center Hospital, Matsuyama, Japan
Accepted for publication March 31, 2004.
* Address reprint requests to Dr Okita, Department of Surgical Oncology, Hiroshima University, Research Institute for Radiation Biology and Medicine, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8553, Japan
rokita{at}hiroshima-u.ac.jp
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Abstract
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Focal ground-glass opacity (GGO) on computed tomography has been reported in several disorders including inflammatory disease and primary neoplastic lesion of the lung. We report a case of malignant melanoma of the nasal cavity metastatic to the lungs in which multiple pulmonary nodules showed GGO. Lung biopsy specimen demonstrated melanoma cells proliferating in a lepidic fashion along the thickened alveolar wall simulating bronchioloalveolar carcinoma. Metastatic lung tumor showing GGO is uncommon.
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Introduction
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We report a case of metastatic lung tumor showing ground-glass opacity (GGO) on high-resolution computed tomography (HRCT). Although focal GGO suggests several disorders including inflammatory disease, fibrosis, or primary lung neoplastic lesion, metastatic lung tumor showing GGO, in particular metastasis from malignant melanoma, is uncommon.
In July 2001, a 56-year-old woman underwent surgical treatment for malignant melanoma localized to the right intranasal cavity. The patient underwent right partial maxillectomy as curative resection. She received oral administration of tegafur-uracil and injection of OK-432 as postoperative adjuvant therapy and had been well for 18 months after the initial operation.
In February 2003, follow-up chest roentgenogram demonstrated an abnormal opacity on the apex of the right lung. On HRCT, multiple GGO lesions with central dense component, ranging from 11 to 28 mm in diameter, were identified in the bilateral lungs (Fig 1A). We strongly suspected either multiple atypical adenomatous hyperplasia or pulmonary adenocarcinoma, although other diagnostic possibilities included communicable disease (bacteria, fungus), sarcoidosis, or malignant lymphoma. After 1 month of observation, most of those GGO had enlarged. Specifically, in the surrounding GGO, 19% enlarged during the month of observation. In contrast, in the central tumor, 227% enlarged. But the total number of GGO lesions did not change.
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Fig 1. (A) A high-resolution computed tomography showing multiple ground-glass opacity lesions in the bilateral lungs. (B) Biopsied lesion. (C–E) A ground-glass opacity lesion showed S-100-positive metastatic melanoma cells lined in a lepidic pattern beneath keratin-7-positive normal alveolar epithelium simulating bronchioloalveolar carcinoma. (C) Hematoxylin & eosin x100 before reduction. (D) Keratin-7 x400 before reduction. (E) S-100 x400 before reduction.
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After preoperative CT-guided pulmonary marking for the lesion at the right upper lobe (Fig 1B), lung biopsy was performed by video-assisted thoracic surgery. Black lesions were recognized at the right lower ventral segment (S6). Lung biopsy at the right upper segment was performed. Histologically, melanoma cells proliferated in a lepidic fashion with a thickened alveolar wall simulating bronchioloalveolar carcinoma (BAC) (Fig 1C). The metastatic nodule did not contained necrotic foci or fibrotic foci. Hemorrhage was not found around the lesion. Immunohistochemically, S-100-positive melanoma cells lined beneath keratin-7-positive normal alveolar epithelium (Figs 1D, 1E). Melanoma cells spread beneath alveolar epithelium without destructive invasion. Therefore, the patient was diagnosed as having metastatic lung tumor from malignant melanoma of the nasal cavity. For 5 months after the lung biopsy the patient received chemotherapy mainly consisting of dacarbazine, without any signs of improvement.
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Comment
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Ground-glass opacity is a finding on HRCT that is defined as a hazy, increased attenuation of the lung with preservation of bronchial and vascular margins [1]. In BAC, GGO is caused by the combined effects of diminished intraalveolar air and increased cellular density, with alveolar cuboidal cell hyperplasia, thickening of the alveolar septa, and partial filling of the terminal air spaces [2]. The differential diagnosis of focal GGO should include inflammatory diseases, focal fibrosis, atypical adenomatous hyperplasia, and adenocarcinoma, but focal GGO due to metastatic tumor is uncommon. Although some cases of metastatic lung tumor showing GGO from adenocarcinoma of the gastrointestinal tract have been reported [3], to our knowledge, only one case of metastatic pulmonary malignant melanoma with a GGO appearance has been reported previously [4].
In our case, the metastatic lesion demonstrated mainly an alveolar displacement growth type pattern with little invasiveness and without hemorrhage. We do not think it likely that the metastatic lesions were formed by direct spread through airway or by lymphatic metastasis. No intraepithelial spread was found in the bronchial epithelium except for the metastatic foci. No lymph nodes metastasis was identified through the history. We speculate that melanoma cells came to the alveoli by the bloodstream and spread beneath the alveolar epithelium. In the primary lesion, melanoma cells showed also intraepithelial growth in nasal respiratory epithelium.
The halo sign of GGO was originally reported to be produced by pulmonary hemorrhage surrounding a central nodule [5]. However, in BAC, malignant lymphoma, and adenocarcinoma metastasis from the gastrointestinal tract, GGO is caused by intraalveolar growth of the tumor. In addition, metastatic malignant melanoma should be considered a possible cause of focal GGO due to not only presenting hemorrhage [4] but presenting intraalveolar growth of the tumor cells simulating BAC.
In our case, most of those GGO lesions enlarged within only 1 month, in particular in the central tumor. Persistent focal GGO after observation for several months is considered a finding of early bronchogenic adenocarcinoma or its precursor [6], the majority of which have a tumor doubling time of longer than 1 year [7]. Therefore, we should suspect metastatic lung tumor when a patient with a history of malignancy has rapid growth of multiple GGO lesions.
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References
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