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Choroid metastases revealing primary clear cell adenocarcinoma of the lung effectively treated with cisplatin and pemetrexed: a case report
© Chang et al.; licensee BioMed Central Ltd. 2013
Received: 24 February 2013
Accepted: 21 August 2013
Published: 11 December 2013
The aim of the present report was to draw the attention of oncologists to the importance of prompt diagnosis of primary clear cell adenocarcinoma of the lung, which allows early initiation of treatment to maintain quality of life.
A 63-year-old Chinese woman initially presented to our facility with multifocal bilateral choroid metastatic lesions that were found to originate from a primary clear cell adenocarcinoma of the lung (T2bN2M1b, stage IV). A thorough ophthalmologic evaluation, study of our patient’s history, imaging studies and comprehensive immunohistochemical staining tests led to the diagnosis of this rare lung tumor.
Although this uncommon cancer is unfortunately already at a late stage when choroid metastases develop, systemic chemotherapy alone is sufficient to preserve vision and gain control over the disease.
Choroid metastasis (CM) is the most common intra-ocular neoplasm in adults, and the most common sites for the primary tumors are the breast and lung [1–4]. The presence of such metastases suggest hematogenous spread, an advanced stage of cancer therefore giving a poor prognosis . The prompt detection of CM is of great significance as, with consideration of the performance status of the patient and location of the primary tumor, it can lead to early implementation of appropriate therapeutic management to improve disease control.
Multiple foci and bilateral involvement are important clinical presentations of CM that can lead to the correct diagnosis of the primary malignancy . Clear cell adenocarcinoma of the lung with an abundant clear cell component is extremely rare, and the associated biological behavior and treatment outcomes for this illness are unknown. Here, we present a case of primary clear cell adenocarcinoma of the lung with multifocal bilateral CM as the initial presentation in an otherwise healthy woman who had a significant and durable response to systemic chemotherapy using cisplatin and pemetrexed.
Systemic chemotherapy with pemetrexed (500mg/m2, every three weeks) and cisplatin (75mg/m2, every three weeks) was initiated. After cycle six of chemotherapy, a fundoscopic examination showed near complete resolution of the choroidal masses, coinciding with improvement in her vision (Figure 1E,F). Although her cancer status outside the orbit remained stable, she had a good quality of life with no chemotherapy maintenance for over 24 months at the time of this report.
Adenocarcinoma with cells that are filled with clear cytoplasm and that are the major component of a lung tumor is defined as primary clear cell adenocarcinoma of the lung according to World Health Organization classification guidelines . Because such pulmonary adenocarcinomas are very small in number, and the cases reported in the literature have shown varied biological natures and clinical presentations , the appropriate diagnostic procedures may help to establish an accurate diagnosis. Firstly, it is so histologically heterogeneous for pulmonary adenocarcinomas that we used video-assisted thoracoscopy to acquire enough tumor tissue, even though a fine-needle aspiration biopsy may enable early diagnosis and hence the initiation of immediate appropriate palliative therapy. Secondly, comprehensive IHC staining studies are required. The tumor tissue from our patient showed monotonous clear cells arranged in a glandular pattern, positive immunoreaction results for AE1/AE3, CK-7, TTF-1, CEA, Ki-67, and positive PAS staining for the existence of glycogen in clear cell cytoplasm. Thus, our patient’s tumor met the criteria for primary clear cell adenocarcinoma of the lung. Finally, our patient’s tumor was distinguished from tumors with clear cell cytoplasm in any organs. Our patient’s tumor was different from renal clear cell carcinoma because there was no tumor found on imaging studies and the tumor cells were negative for CD10 staining. It was not a benign clear cell sugar tumor because it was malignant and the tumor cells were negative for HMB-45. Our patient’s case was not one of clear cell squamous cell carcinoma in terms of histological features and negative staining for p63. It was obviously not a pulmonary blastoma or fetal adenocarcinoma because no fetal features were present. Our patient’s tumor was not a metastatic thyroid papillary clear cell carcinoma because there was no tumor found in the thyroid glands and no expression of thyroglobulin. Our patient’s case was not one of clear cell sarcoma, malignant melanoma, sex-cord tumor and metastatic hepatocellular carcinoma, alveolar soft part tumor and metastatic carcinomas of the gastrointestinal tract because there was negative staining for HMB-45, S-100, α-inhibin, Hep-par-1, glypican-3, CDX2, TFE-3 and vimentin. Taken as whole, our patient’s clinical presentation, imaging study results and thorough investigation of pathological features and IHC stainings were sufficient to confirm the diagnosis of her tumor as a primary clear cell adenocarcinoma of the lung with multifocal and bilateral CM, even without a choroid biopsy.
The incidence of CM for lung cancer is reported to be no more than 7 percent . In such a condition, the lung cancer is already at a late stage and dissemination of the disease has occurred; the median survival after diagnosing symptomatic CM is 4.3 to 7.4 months . Hence, the goals of treatment are to improve quality of life and preserve vision, which can be achieved by either systemic chemotherapy or target therapy based upon the performance status and the histologic subtype. It has been demonstrated that inhibition of the epidermal growth receptor (EGFR) pathway with tyrosine kinase inhibitors (TKIs) provides effective treatment and improved tolerability for non-small-cell lung cancers, especially for a subset of female patients of East Asian origin who are never smokers and have an adenocarcinoma histology, and who have high prevalence of sensitive activating EGFR mutations (deletion in exon 19 or point mutation of L858 in exon 21) . However, TKIs were not considered since the tumor specimen from our patient failed to show the aforementioned EGFR mutation.
It has been reported that systemic chemotherapy is efficacious for choroid metastases from non-small-cell lung cancer [11, 12]. In our patient’s case, standard platinum doublet chemotherapy was used as the initial and primary treatment because our patient had other concurrent sites of metastatic disease that required simultaneous attention. Further, cisplatin plus pemetrexed has shown survival benefits in pulmonary adenocarcinoma . Although the tumor remained stable, our patient gained visual improvement and acceptable disease control via this platinum doublet chemotherapy. Taken together, these findings suggest the choroid may be no longer considered as a ‘sanctuary site’ to chemotherapy, and systemic chemotherapy alone is a useful therapeutic option for CM of lung cancer.
The prognosis and treatment choices for primary clear cell adenocarcinoma of the lung may resemble those for non-small-cell lung cancer. Because the disease is rare and glycogen-rich clear cells display an unusual histology, the prognosis and treatment outcome may be more complicated. Even though a patient may initially present with multiple metastases including the choroidal type, as in our patient’s case, immediate initiation of histologically-adapted chemotherapy may yield clinical benefits and improvements in quality of life. To the best of our knowledge this is the first report demonstrating that the efficacy and safety of systemic doublet chemotherapy with cisplatin plus pemetrexed for choroidal metastasis of primary clear cell adenocarcinoma of the lung.
In summary, we present a rare occurrence of clear cell adenocarcinoma of the lung that needed to be confirmed and differentiated from clear cell cancer from other organs by systemic investigation and intensive IHC staining tests. CM may be the initial sign of this rare tumor and the ophthalmologic diagnosis may lead to the discovery of the systemic affliction, albeit unfortunately at a late stage of the disease. If compatible with the patient’s general status, appropriate chemotherapy may be an efficacious mode of treatment in advanced stages of this rare and metastatic lung cancer.
Written informed consent was obtained from the patient for publication of this manuscript and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.
This study was partially supported by grants (CMRPG280131 and CMRP280132) from the Chung Gang Memorial Hospital.
Our patient’s case was reviewed and we were given clearance for publication by the Institutional Review Board, Chang Gung Memorial Hospital.
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