We would like to report visual disturbance due to choroidal metastasis as the first clinical sign of renal carcinoma.

Metastatic tumours are one of the most common type of intraocular malignancy in adults with the most common origins of metastasis being the lungs in men and breasts in women

.Ocular choroidal metastases from renal cell carcinoma (RCC)are rare with 3.5% of ocular metastases originating from the kidneys

. RCC predominantly occurs in individuals in their seventh and eighth decades of life and has been reported nearly twice as often in men as in women

.

我們嶺北鎮(zhèn)是個(gè)小鎮(zhèn)，我們嶺北鎮(zhèn)的學(xué)校也小，老師也少，這樣說的意思關(guān)鍵是說我們嶺北鎮(zhèn)的老師很少來家訪。通常在我們的印象里，老師今天去了誰家了，誰家的孩子一定就是犯事了。而今天，李老師到了周小羽家了。

Visual disturbance and metamorphopsia as the first clinical signs of renal cancer with multi-organ metastasis, according to our knowledge, has been described in only a few cases. Other rare sites of RCC metastases include the pancreas, thyroid,skeletal muscle, skin or underlying soft tissues with these sites of metastasis rarely occurring simultaneously

. This is the first documented case of coexistence of very rare sites of metastasis in patients with RCC namely choroid and the skin.

CASE REPORT

During a general examination there were no clinical signs of anaemia, icterus or oedema. Complete blood cell count,bleeding time, urine analysis, serum electrolytes, routine blood hepatic and renal function tests were all within normal ranges.Hemogram and biochemical test results were also within normal limits.

Standard ophthalmologic examination revealed reduced visual acuity in the left eye measuring 0.3 (cc +1.00 dsph on Snellen chart) and normal right eye visual acuity. Intraocular pressure,ocular motility and biomicroscopy were normal. Dilated fundus examination of the left eye showed a creamy yellow,dome-shaped mass in the posterior pole on the superotemporal edge of the macula surrounded with serous retinal detachment(Figure 1A)

In the early phase of fluorescein angiography(FA) small vessels within the tumour were revealed (Figure 1B) with dye leakage in the late phase (Figure 1C) confirming a choroidal tumour of metastatic origin and the site of the primary tumour being unknown.

MDCT of the thorax revealed multiple focal nodular changes of lung parenchyma diffusely distributed on both sides primarily corresponding to metastatic lesions (Figure 2C).Confluent necrotic extensive hilar lymphadenopathy on both sides and osteolytic lesions of margo inferior of the right scapula were also presented (Figure 2D, 2E).

A 46-year-old male patient noticed left eye visual disturbances and metamorphopsy without any other systemic symptoms.Apart from posttraumatic stress disorder and painless hematuria reported six months prior to initial ophthalmological examination the patient had no previous history of illness and no current health issues.

Pathohistology of the skin tumour revealed adenocarcinoma composed of solid areas and abortive glandular structures(Figure 3A, 3B). A transbronchial lung biopsy was also performed showing both tumour samples having an identical immunohistochemical profile. Tumours were immunohistochemically positive for the CK7 marker (Figure 3C, 3D), and negative for the CK20, CK5/6, TTF-1, Napsin A,AMACR, CD10, CD117, and vimentin.

1.4.1 氣泡量 出艙后 10、20、30、40、60、90 min 時(shí)行超聲檢查，觀察流經(jīng)右心室的氣泡量1 min 并計(jì)數(shù)。根據(jù) Eftedal-Brubakk 評分方法[7]對氣泡量評分：未觀測到氣泡記 0 分；偶爾出現(xiàn)氣泡記 1 分；每 4 個(gè)心動(dòng)周期至少出現(xiàn) 1 個(gè)氣泡記2 分；每個(gè)心動(dòng)周期至少出現(xiàn) 1 個(gè)氣泡記 3 分；視野中氣泡個(gè)數(shù)為 1/cm2 記 4 分；滿屏氣泡，無法辨認(rèn)單個(gè)氣泡記 5 分。

（2）沒有統(tǒng)一的研發(fā)標(biāo)準(zhǔn)，水平參差不齊、不規(guī)范。各平臺在不同程序、不同接口技術(shù)、不同標(biāo)準(zhǔn)下研發(fā)，導(dǎo)致實(shí)驗(yàn)項(xiàng)目場景逼真度、趣味性、操作性、規(guī)范性差別較大，平臺建設(shè)水平高低不一，二次開發(fā)困難，軟件對接性、共享性較差。

Multiple detector computer tomography (MDCT) of the abdomen showed the right kidney entirely infiltrated by necrotic tumour mass with blurred anterolateral contour of the upper part spreading through the right renal sinus. There was no renal vein thrombosis, however a channel system of the upper and medium groups of calices and renal pelvis were infiltrated by tumour tissue. On the lower part of the left kidney a suspect tumorous infiltration was also found (Figure 2A, 2B).

小語種導(dǎo)游之所以緊俏，也源于小語種人才的緊俏。因此，小語種導(dǎo)游，尤其是兼職小語種導(dǎo)游，要有效利用高校小語種人才資源[3]。小語種人才聚集最多的地方便是開設(shè)有小語種課程的高校，充分利用高?，F(xiàn)有小語種學(xué)生人才，既能讓小語種學(xué)生發(fā)揮其專業(yè)優(yōu)勢，學(xué)以致用，為學(xué)生創(chuàng)造力一個(gè)社會實(shí)踐及經(jīng)濟(jì)獨(dú)立的機(jī)會，又極大地緩解了旅游市場上外語導(dǎo)游荒的困境，這能在很大程度上能夠解決小語種導(dǎo)游緊缺的困擾。

Pathological analysis of the tumour tissue due to CK7 positivity confirmed that it was an adenocarcinoma. CK7 is a keratin marker expressed in many adenocarcinomas, including adenocarcinoma of the lungs as well as several histological types of RCC

. Primary carcinoma in the lungs was excluded due to TTF-1 and Napsin A negativity since double Napsin A and TTF-1-positive immunostaining is highly specific for primary adenocarcinoma of the lungs

. Radiological diagnostics, clinical data and immunohistochemical analysis implicated that the primary tumour site was the kidneys.However, the morphology of the tumour does not correspond to the classifications of recognized RCC histological subtypes.As the primary kidney tumour metastasized to the lungs,bones, skin and eye cisplatin-etopozid chemotherapy protocol was prescribed by an oncologist. However, general health status deteriorated and the patient died due to widespread metastatic disease two months after the diagnosis, receiving only one cycle of chemotherapy.

DISCUSSION

We presented an extremely rare case of a primary renal adenocarcinoma in which the initial symptoms were decreased visual acuity and metamorphopsia. The choroid is an uncommon site for RCC metastasis and this lesion can be difficult to differentiate from a primary choroid carcinoma.Ocular metastases whilst rare may be the first symptom of RCC and thus a thorough medical history, ophthalmological and general physical examination should be performed in every questionable case. To our knowledge, this is the first documented case of simultaneous existence of very rare sites of metastasis in patients with RCC, namely choroid and the skin. The prognosis in this situation is generally poor with median survival being shorter than six months in the case of skin metastases and less than eight months in the case of choroidal metastases

. This poor prognosis was also confirmed in our case since the patient unfortunately passed away only two months after being presented to the ophthalmology department. The localization of the metastasis on the skin in our patient facilitated taking a tissue sample for pathohistological evaluation. Pathological analysis of the tumour tissue confirmed that the tumour was an adenocarcinoma and according to radiological and clinical data, most likely of renal or lung origin. Immunostaining with TTF-1 and Napsin A excluded the lungs as the primary site of the tumour and led us to the conclusion that the primary tumour was of renal origin with metastasis to the lungs, bones, liver,adrenal glands, skin and the left eye. Immunohistochemical analysis for the traditional RCC markers namely AMACR,CD117, CD10 and vimentin standardly used in differentiating subtypes of RCC was negative making it difficult to determine the exact type of kidney tumour

. It is known that even after immunohistochemical evaluation approximately 5%of tumours remain unclassified. Possible explanations are that the tumour is purely sarcomatoid, that the immune profile is not final or that there are unusual or overlapping morphological features

. According to pathological and immunohistochemical analysis we concluded that in our case it was an unclassified RCC which represents 2%-6% of RCCs

.An alternative explanation could be that the tumour may have lost characteristic morphological features and immune profile in the metastatic setting, making confirmation of the renal origin and tumour subtyping difficult

.

Ocular metastasis may be the first sign of systemic malignancies even in the absence of visible symptoms or signs of a primary tumour. In this paper, we highlighted the importance of considering the existence of metastatic disease when detecting subretinal lesions of unknown aetiology during regular eye examinations due to reported visual disturbances. This fact suggests that ophthalmologists may have a key role in timely diagnosis and proper treatment of serious systemic illness.

ACKNOWLEDGEMENTS

None;

None;

None;

None;

None;

None.

1 Shome D, Honavar SG, Gupta P, Vemuganti GK, Reddy PVA.Metastasis to the eye and orbit from renal cell carcinoma—a report of three cases and review of literature.

2007;52(2):213-223.

2 Ka?telan S, Gverovi?-Antunica A, Beketi?-Ore?kovi? L, Bakija I, Bogadi M. Uveal melanoma: clinical features and diagnostic procedures.

2017.

3 Aydin H, Chen L, Cheng L, Vaziri S, He H, Ganapathi R, Delahunt B, Magi-Galluzzi C, Zhou M. Clear cell tubulopapillary renal cell carcinoma: a study of 36 distinctive low-grade epithelial tumors of the kidney.

2010;34(11):1608-1621.

4 Kuroda N, Tanaka A, Ohe C. Recent advances of immunohistochemistry for diagnosis of renal tumors.

2013;63(8):381-390.

5 Ye J, Findeis-Hosey JJ, Yang Q, McMahon LA, Yao JL, Li F, Xu H.Combination of napsin A and TTF-1 immunohistochemistry helps in differentiating primary lung adenocarcinoma from metastatic carcinoma in the lung.

2011;19(4):313-317.

6 Sountoulides P, Metaxa L, Cindolo L. Atypical presentations and rare metastatic sites of renal cell carcinoma: a review of case reports.

2011;5:429.

7 Rao BV, Regulavalasa T, Fonseca D, Murthy SS, Sharma R, Raju KVVN, Rao TS, Sundaram C. Differentiation of renal cell tumors with morphological cocktails using a minimal panel of immunohistochemical markers.

2020;12(3):236-240.

8 Warren AY, Harrison D. WHO/ISUP classification, grading and pathological staging of renal cell carcinoma: standards and controversies.

2018;36(12):1913-1926.

9 Lopez-Beltran A, Kirkali Z, Montironi R, Blanca A, Algaba F, Scarpelli M, Yorukoglu K, Hartmann A, Cheng L. Unclassified renal cell carcinoma: a report of 56 cases.

2012;110(6):786-793.

10 Sirohi D, Smith SC, Agarwal N, Maughan BL. Unclassified renal cell carcinoma: diagnostic difficulties and treatment modalities.

2018;10:205-217.