What Are the Most Common Esophageal Metastases

FIGURE 1 Esophagram: Distal Esophageal Stenosis with Proximal Dilation (A1 and A2)

FIGURE 2 Esophageal Biopsy.

TABLE Case Series and Autopsies Reports on Esophageal Metastases

Dr. Bolaño is Medical Oncology Fellow, Hemato-Oncology Department Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.

Dr. Castro-Alonso is Researcher, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.

Dr. Martíenz-Benitez is Assistant Professor. Pathology Department. Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.

A rare occurrence, cancer in the esophagus requires an individualized treatment plan.

THE CASE

A 63-year-old man presented with a 3-month history of significant weight loss, dysphagia, and odynophagia. His past medical history was relevant for a radical cystectomy for a stage II muscle-invasive urothelial bladder cancer 10 years ago. He had an hepatic, pulmonary, and lymph-node systemic recurrence 8 years ago, with complete response to 6 cycles of gemcitabine/carboplatin, and has been in continuous surveillance ever since.

His physical examination and laboratory tests were unremarkable. An esophagram revealed distal esophageal stenosis with proximal dilation. A CT scan showed a concentric thickening in the middle and distal esophagus. Positron emission tomography and F-18-fluorodeoxyglucose (18F-FDG) integrated with CT (18F-FDG PET/CT) displayed hypermetabolism in the middle and distal third of the esophagus, with no evidence of other sites of metastatic disease (Figure 1).

An upper gastrointestinal endoscopy was performed and revealed a complex ulcerated stenosis at 35 cm from the upper incisors. Biopsies were taken. The pathology examination revealed metastatic high-grade urothelial carcinoma: CK7-positive, CK20-negative, GATA3-positive, p63-positive, and uroplakin-positive (Figure 2). Morphologic appearance and immunohistochemistry were highly similar to that of the primary tumor and the previous systemic recurrence.

What is the primary tumor that most commonly metastasizes to the esophagus?

A. Breast Cancer

B. Lung Cancer

C. Kidney Cancer

D. Urothelial Cancer

Correct Answer: B. Lung cancer is the primary tumor that most often causes secondary infiltration to the esophagus.

Discussion

Esophageal metastases are a rare phenomenon. According to autopsy registries of any kind of neoplasm, incidence ranges from 0.3% to 6.1% of all metastases, most of them asymptomatic.[1,2] Esophageal involvement may be caused by three principal mechanisms: direct extension, mediastinal lymph node metastases with subsequent esophageal infiltration, and hematogenous dissemination. Direct extension from adjacent organs is by far the most common manifestation (up to 45.2% of cases), followed by infiltration from mediastinal lymphatic metastases (35.5% of cases). True distant hematogenous metastases are the rarest mechanism, accounting for 19.3% of cases.[3] Direct extension from a contiguous organ can be recognized most of the time by the obvious primary tumor. This does not hold true for the other two mechanisms, and therefore most clinical series admix them.[3]

The first case of esophageal metastasis (from the prostate) was published by Gross and Freedman in 1942.[4] After that, a wide array of malignant tumors with metastases to the esophagus were reported, including lung, breast, ovarian, kidney, gastrointestinal, lymphoma, testicular, tongue, bone, liver, uterine, and skin.[2,3] According to the largest retrospective autopsy case series, the most common cause of esophageal metastases is lung cancer, followed by breast and gastric neoplasms (45.5%, 12.5%, and 11.6% of all esophageal metastases, respectively).[2] This study and other case series are summarized in the Table. Thus, option B is correct, but histologic differences need to be addressed. Up to 15% of adenocarcinomas metastasize to the esophagus and the corresponding percentages for small-cell lung cancer and squamous cell carcinoma are 9.8% and 8.1%, respectively.[2]

Urothelial carcinoma is the 10th most common malignant neoplasia worldwide.[5] About 10% to 20% of those patients have the aggressive muscle-invasive disease, which gives them higher risk of lymphatic and systemic dissemination.[6,7] Even with curative treatments like radical cystectomy, up to 16% and 50% will have locoregional and distant recurrences, respectively.[8–10] The most common sites of distant metastases from urothelial carcinoma are nonregional lymph nodes (90%), liver (47%), lung (45%), and bone (32%); other sites might include peritoneum, pleura, kidney, adrenal gland, and intestine.[11] To the best of our knowledge, this is the first case report of esophageal metastasis ever reported.

Esophageal metastases are a diagnostic challenge, because in most cases clinical presentation is indistinguishable from primary esophageal cancers. No difference in the severity or duration of symptoms correlates to primary versus secondary neoplasms.[2] Radiographic studies might be useful to detect primary adjacent tumors, but these are not that useful to discriminate metastasis from primary neoplasms. Esophagrams can display esophageal stenosis with normal mucosa, and CT scans may show concentric thickening of the esophageal wall, with or without an associated extrinsic mass.[2,3]

Upper gastric endoscopy is the most useful test in this setting. A normal epithelium is seen in 68% of esophageal stenosis due to the submucosal nature of most metastases. In any esophageal stenosis with normal mucosa, metastasis must be contemplated as a differential diagnosis, especially in patients with a history of cancer. Endoscopic ultrasound might also help to determine the layer where a tumor comes from and also to achieve histopathologic diagnosis, as many traditional endoscopy biopsies might only show normal epithelium overlying to the tumor.[2,11,12]

Treatment of esophageal metastases depends on several factors, such as origin, symptom severity, and presence of metastases to other organs. In most patients, treatment consists of chemotherapy with or without radiotherapy.[2] Although chemosensitive, most metastatic urothelial carcinomas remain an incurable disease. Without systemic treatment, most patients die of progressive disease within 6 months.[13] The cornerstone of treatment for urothelial cancer is platinum-based chemotherapy, achieving an objective response rate of 50% to 60% and complete responses in 10% to 20% of patients. In most cases, responses are transitory and few patients achieve long-term survival.[8,9,13]

Local control with esophagectomy has provided excellent palliation in several case reports of esophageal metastases, with primary tumors coming from breast, lung, and malignant melanoma.[10,14,15] Metastasectomy in urothelial carcinoma and its impact in survival is controversial.[15,16] Single-site metachronous tumors have achieved prolonged survival in case reports, however, so an aggressive surgical approach must be taken into consideration. Palliation with endoscopic dilation and stents might be an alternative, given that many patients have maintained oral intake with those procedures in recent reports of esophageal metastases.[3,17,18]

Prognosis of esophageal metastases is uncertain, ranging from a few months to several years. A case-by-case detailed analysis must be done in every patient to select the proper treatment and attain quality of life.

Key Points

• Esophageal metastases are a rare phenomenon, ranging from 0.3% to 6.1% of all metastases.

• The most common cause of esophageal metastases is lung cancer, followed by breast and gastric neoplasms.

• In esophageal stenosis with normal mucosa, metastasis must be considered as a differential diagnosis, especially if the patient has a previous history of cancer.

• There is no standard treatment for esophageal metastases; a case-by-case selection for aggressive treatment must be considered.

Outcome of This Case

The patient was started on chemotherapy with gemcitabine and carboplatin, given the adequate clinical response he had had to this combination previously and the fact that he could sustain adequate oral intake despite his symptoms. Currently, he has received 2 cycles of chemotherapy with adequate tolerance. A control CT scan to ascertain response is pending.

Financial Disclosure: The other authors have no significant financial interest in or other relationship with the manufacturer of any product or provider of any service mentioned in this article. Dr. María Bourlon has served as a speaker and a member of the advisory board for Bristol-Myers Squibb. She has been a speaker, advisor, and/or travel grant recipient for BMS, Janssen, Ipsen, MSD, and Asofarma.

FIVE KEY REFERENCES

6. Dietrich B, Siefker-Radtke AO, Srinivas S, Yu EY. Systemic therapy for advanced urothelial carcinoma: current standards and treatment considerations. Am Soc Clin Oncol Educ Book. 2018;38:342-53.

7. Shankar PR, Barkmeier D, Hadjiiski L, Cohan RH. A pictorial review of bladder cancer nodal metastases. Transl Androl Urol. 2018;7:804-13.

11. Hiensch R, Belete H, Rashidfarokhi M, et al. Unusual patterns of thoracic metastasis of urinary bladder carcinoma. J Clin Imaging Sci. 2017;7:23.

12. Fan W, Jiang H, Chen H, et al. Esophageal metastasis from endometrial adenocarcinoma: a case report and literature review. Transl Cancer Res. 2018;7:1178-83.

15. Patel V, Collazo Lorduy A, Stern A, et al. Survival after metastasectomy for metastatic urothelial carcinoma: a systematic review and meta-analysis. Bladder Cancer. 2017;3:121-32.

FAST FACTS about Esophageal Cancer

• Esophageal cancer is the 7th most common cancer worldwide.

• When esophageal cancer occurs, it starts in the inner layers of the esophagus and grows outward.

• Other cancers metastasizing to the esophagus is a rare occurrence, but symptoms are often similar to those in primary esophageal cancer.

• Cancer affecting the esophagus can sometimes narrow the esophagus which may make it difficult to swallow or eat properly.

• Other signs and symptoms of esophageal cancer or cancer metastasized to the esophagus include heartburn, unexplained weight loss, hiccups, or a lasting cough.

• An esophagectomy, surgery to move all or part of the esophagus, is a common treatment for esophageal cancer.

• While recovering from surgery, patients with cancer in the esophageal may not be able to eat by mouth and need a feeding tube to meet their nutritional needs.

• Barrett esophagus is a pre-cancerous condition in which the cells at the lower part of the esophagus have been replaced by abnormal cells due to damage by stomach acid from reflux. People with Barret esophagus are at higher risk for esophageal cancer.

• There are approximately 17,000 new esophageal cancer diagnoses each year in the USA.

• Esophageal cancer is 3-4 times more common in men than women

References:

1. Abrams HL, Spiro R, Goldstein N. Metastases in carcinoma: analysis of 1000 autopsied cases. Cancer. 1950;3:74-85.

2. Mizobuchi S, Tachimori Y, Kato H, et al. Metastatic esophageal tumors from distant primary lesions: report of three esophagectomies and study of 1835 autopsy cases. Jpn J Clin Oncol. 1997;27:410-4.

3. Simchuk EJ, Low DE. Direct esophageal metastasis from a distant primary tumor is a submucosal process: a review of six cases. Dis Esophagus. 2001;14:247-50.

4. Gross P, Freedman LJ. Obstructing secondary carcinoma of the esophagus. Arch Pathol Lab Med. 1942;33:361-4.

5. International Agency for Research on Cancer. World Health Organization. Asia. Source: Globocan 2018. May 2019: Global Cancer Observatory.

6. Dietrich B, Siefker-Radtke AO, Srinivas S, Yu EY. Systemic therapy for advanced urothelial carcinoma: current standards and treatment considerations. Am Soc Clin Oncol Educ Book. 2018;38:342-53.

7. Shankar PR, Barkmeier D, Hadjiiski L, Cohan RH. A pictorial review of bladder cancer nodal metastases. Transl Androl Urol. 2018;7:804-13.

8. Galsky MD, Chen GJ, Oh WK, et al. Comparative effectiveness of cisplatin-based and carboplatin-based chemotherapy for treatment of advanced urothelial carcinoma. Ann Oncol. 2012;23:406-10.

9. Sternberg CN, de Mulder P, Schornagel JH, et al; EORTC Genito-Urinary Cancer Group. Seven year update of an EORTC phase III trial of high-dose intensity M-VAC chemotherapy and G-CSF versus classic M-VAC in advanced urothelial tract tumours. Eur J Cancer. 2006;42:50-4.

10. Inoshita T, Youngberg GA, Thur de Koos P. Esophageal metastasis from a peripheral lung carcinoma masquerading as a primary esophageal tumor. J Surg Oncol. 1983;24:49-52.

11. Hiensch R, Belete H, Rashidfarokhi M, et al. Unusual patterns of thoracic metastasis of urinary bladder carcinoma. J Clin Imaging Sci. 2017;7:23.

12. Fan W, Jiang H, Chen H, et al. Esophageal metastasis from endometrial adenocarcinoma: a case report and literature review. Transl Cancer Res. 2018;7:1178-83.

13. von der Maase H, Hansen SW, Roberts JT, et al. Gemcitabine and cisplatin versus methotrexate, vinblastine, doxorubicin, and cisplatin in advanced or metastatic bladder cancer: results of a large, randomized, multinational, multicenter, phase III study. J Clin Oncol. 2000;18:3068-77.

14. Eng J, Pradhan GN, Sabanathan S, Mearns AJ. Malignant melanoma metastatic to the esophagus. Ann Thorac Surg. 1989;48:287-8.

15. Patel V, Collazo Lorduy A, Stern A, et al. Survival after metastasectomy for metastatic urothelial carcinoma: a systematic review and meta-analysis. Bladder Cancer. 2017;3:121-32.

16. Iwamoto H, Izumi K, Shimura Y, et al. Metastasectomy improves survival in patients with metastatic urothelial carcinoma. Anticancer Res. 2016;36:5557-61.

17. Atkins JP. Metastatic carcinoma to the esophagus: endoscopic considerations with special reference to carcinoma of the breast. Ann Otolaryngol. 1966;75:356-67.

18. Knyrim K, Wagner HJ, Bethge N, Keymling M, Vakil N. A controlled trial of an expansile metal stent for palliation of esophageal obstruction due to inoperable cancer. N Engl J Med. 1993;329:1302-7.

19. Agha FP. Secondary neoplasms of the esophagus. Gastrointest Radiol. 1987;12:187-93.