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Japanese Journal of Clinical Oncology Pages 494-497

Undifferentiated Carcinoma with Lymphoid Infiltration of the Esophagus: a Case Report
Introduction
Case Report
   Pathology
Discussion
References
Undifferentiated Carcinoma with Lymphoid Infiltration of the Esophagus: a Case Report

Undifferentiated Carcinoma with Lymphoid Infiltration of the Esophagus: a Case Report

Katsuhiko Shimizu1, Wataru Takiyama1, Koichi Mandai2, Minoru Tanada1, Yoshiharu Kawabuchi1 and Yuji Heike3

Departments of 1Surgery, 2Pathology and 3Internal Medicine (Clinical Research), National Shikoku Cancer Center Hospital, Matsuyama, Japan

This paper reports a surgically treated case of undifferentiated carcinoma with lymphoid infiltration of the esophagus. Histologically, most of the tumor consisted of undifferentiated carcinoma (non-small cell type) with lymphoid infiltration and a small portion showed features of poorly differentiated squamous cell carcinoma. Carcinoma with lymphoid infiltration in the stomach, breast or nasopharynx has a good prognosis, but in the esophagus this histological type is extremely rare and its characterization is unclear. This is only the sixth report to date of undifferentiated carcinoma with lymphoid infiltration of the esophagus.

Key words: esophageal carcinoma - undifferentiated carcinoma (non-small cell type) - lymphoid infiltration

INTRODUCTION

The most common histological type of primary esophageal carcinoma in Japan is squamous cell carcinoma and other types, including undifferentiated carcinoma, are relatively rare. In the stomach and breast, undifferentiated medullary carcinoma with lymphoid infiltration has been shown to have a good prognosis (1,2), but in the esophagus this histological type is extremely rare and its characterization unclear. In most cases, undifferentiated carcinoma of the esophagus generally results in a poor prognosis and usually is not associated with lymphoid infiltration (3). In this report, we describe a recently encountered case of undifferentiated carcinoma with lymphoid infiltration of the esophagus.

CASE REPORT

A 72-year-old man was admitted to the National Shikoku Cancer Center Hospital on July 2, 1998, complaining of severe dysphagia. Ten years earlier, he had undergone a total gastrectomy (Roux-en-Y reconstruction) for treatment of gastric carcinoma. Its pathological stage was T3 N1 M0 Stage IIIA (TNM Classification of the Stomach) (4). There was no evidence of recurrence over the subsequent 10 years. Over 40 years prior to presentation at our hospital, he had smoked two packs of cigarettes and drunk 250 ml of Japanese sake per day. He did not show evidence of any recent weight loss. Physical examination revealed no anemia, jaundice, palpable supraclavicular lymph nodes or other abnormalities. The laboratory data and the following tumor markers were also within normal limits: CEA 2.6 ng/ml (normal value <5 ng/ml), CA19-9 6.6 U/ml (<37.0 U/ml), SCC 0.7 ng/ml (<1.5 ng/ml), NSE 5.9 ng/ml (<10.0 ng/ml) and CYFRA 1.4 ng/ml (<3.5 ng/ml). A barium swallow showed a circular elevated tumor from the midthoracic esophagus to the esophago-jejunostomy (Fig. 1). Upper gastrointestinal endoscopy revealed a circular elevated lesion with central depression 38 cm from the incisor. Most of the tumor did not stain with Lugol's solution. The biopsy specimens from the esophageal elevated lesion revealed basophilic cancer cells arranged in solid nests or trabecula, supporting a diagnosis of undifferentiated carcinoma. Computed tomography revealed a mid-thoracic esophageal mass but no evidence of mediastinal or cardiac lymph adenopathy, pulmonary metastasis or liver metastasis. Based on these findings, the clinical stage was determined as T3 N0 M0 Stage IIA (TNM Classification of the Oesophagus) (4) and surgical resection was considered appropriate. On July 22, 1998, a transhiatal esophagectomy was performed because of poor pulmonary function (vital capacity 56.8%) and an esophageal reconstruction with a free autograft of the jejunum (ante-thoracic route) was performed because of colon adhesion. The surgical stage was T3 N1 (lower thoracic paraesophageal lymph node) M0 Stage III. The patient had an uneventful postoperative course and was discharged on the 70th day after surgery. He has been free from cancer for 10 months since his operation.


Figure 1. Barium swallow showing a circular elevated tumor with central depression from the mid-thoracic esophagus to the esophago-jejunostomy.

Pathology

Macroscopically, an 8.0 × 7.5 cm ulcerative and infiltrative type of tumor was observed from the mid-thoracic esophagus to the esophago-jejunostomy (Fig. 2) and showed definite invasion reaching the adventitia. Most of the tumor surface did not stain with Lugol's solution. The cut surface of the carcinoma was homogeneously gray. A low-power microscopic view (H-E stain ×10) showed an expansive growth of the tumor extending to the adventitia (Fig. 3). A high-power microscopic view (H-E stain ×50) showed a solid nest structure of cancer cells and substantial infiltration of lymphoid cells into the stroma (Fig. 4). Histologically, most of the tumor consisted of undifferentiated carcinoma (non-small cell type) with lymphoid infiltration and a small portion showed features of poorly differentiated squamous cell carcinoma. A metastasis was found microscopically in one of the resected lower paraesophageal lymph nodes. The pathological stage was T3 N1 M0 Stage III.


Figure 2. An 8.0 × 7.5 cm ulcerative and infiltrative type of tumor was observed in the resected specimen.


Figure 3. Low-power microscopic view showing an expansive growth of the tumor extended to the adventitia (H-E stain ×10).


Figure 4. High-power microscopic view of the tumor showing a solid nest structure of cancer cells and substantial infiltration of lymphoid cells into the stroma (H-E stain ×50).

DISCUSSION

In 1949, Moore and Foote first described a well-circumscribed form of breast carcinoma with a lymphoid stroma (1). It was called medullary breast carcinoma and was observed to have a better prognosis than other histological types. Carcinomas of a similar appearance have been reported to occur in the stomach. In 1948, Steiner et al. used the term `blue cell cancer' to describe such carcinomas and to emphasize their histological and prognostic distinctiveness (5). In 1968, Hamazaki et al. used the term `medullary carcinoma with lymphoid infiltration' to emphasize the close resemblance between these tumors and breast carcinoma (2). They found medullary carcinoma with lymphoid infiltration in 1.3% of a total of 365 cases of resected gastric carcinoma. In 1976, Watanabe et al. used the term `gastric carcinoma with lymphoid stroma' and reported this histology in 4% of a total of 1041 cases of resected gastric carcinoma (6). On the other hand, in 1979, Shanmugaratnam et al. reported the occurrence, in the nasopharyngeal region, of squamous cell carcinoma, non-keratinizating carcinoma and undifferentiated carcinoma with lymphocytic infiltration (7). Much as in breast carcinoma, gastric carcinoma and nasopharyngeal carcinoma, in esophageal carcinoma the histological finding of `carcinoma with lymphoid infiltration' is extremely rare. To our knowledge, esophageal carcinoma with lymphoid infiltration is an extremely rare histological type, with only five cases having been reported so far in the literature in Japan (8-12) (Table 1).

Table 1. Reported cases of esophageal carcinoma with lymphoid infiltration in Japan
Authors Age/ gender Gross feature Histological feature Pathological stage Prognosis
Amano et al., 1988 (8) 59/M Slightly depressed type Poorly differentiated squamous cell carcinoma TisN0M0 Not described
Mori et al., 1989 (9) 70/M Flat type Poorly differentiated squamous cell carcinoma T2N0M0 2 years alive
Mizutani et al., 1991 (10) 65/M Ulcerative and localized type Undifferentiated carcinoma (non-small cell type) T3N0M0 4 years alive
Morimoto et al., 1993 (11) 56/M Predominantly subepithelial type Undifferentiated carcinoma (non-small cell type) T1N0M0 2 years 4 months alive
Kanki et al., 1997 (12) 75/F Predominantly subepithelial type Undifferentiated carcinoma (non-small cell type) T3N1M1 3 years 5 months alive
Our case 72/M Ulcerative and localized type Undifferentiated carcinoma (non-small cell type) T3N1M0 10 months alive

The histological criteria reported by Hamazaki et al. (2) for this type of carcinoma were (i) intercellular edema and lymphoid cell infiltration of the tumor parenchyme, (ii) lymphoid feature of the tumor stroma and (iii) uniformity in distribution of these elements in the tumor. Watanabe et al. (6) reported that the histological characteristics of this carcinoma were (i) parenchymal pattern microalveolar, trabecular or primitive tubular, (ii) uniformly dense and diffuse lymphoid-cell infiltration, (iii) no marked atypism of tumor cells and (iv) follicular hyperplasia in the regional lymph nodes. The present case showed both sets of characteristic patterns.

Lymphoid infiltration is considered to be a manifestation of the host reaction to tumor growth (6). The stromal infiltrate is composed primarily of lymphocytes and plasma cells. These cells may play a role in host resistance and the lymphoid infiltration may be the histological manifestation of an intensive host resistance.

Cases of gastric carcinoma with lymphoid stroma (GCLS) have a good outcome. Watanabe et al. (6) reported that the relative 5-year survival rate was 100% for cases with submucosal invasion, 95.9% for those with muscle invasion and 73.2% for those with serosal invasion. The difference in the survival rate between GCLS and ordinary stroma with serosal invasion was highly significant (73.2 vs 39.4%, P < 0.001) (6). Nakamura et al. (13) reported that the 5-year survival rate was 84% for patients with GCLS and 58% for patients with ordinary carcinoma and the two groups showed a significant difference (P < 0.05). In early carcinomas the survival rate did not differ between the two groups, but in advanced carcinomas GCLS showed a significantly better prognosis than ordinary carcinoma (83 vs 46%, P < 0.05) (13).

Cases of nasopharyngeal carcinoma with lymphoid infiltration also have a good outcome. Shanmugaratnam et al. (7) reported that the 3-year survival rate for tumors with lymphocytic infiltration (45.8%) was better than that for tumors with moderate lymphocytic infiltration (32%) or no lymphocytic infiltration (26.7%) (P < 0.05).

In esophageal carcinoma, a close correlation was demonstrated between the postoperative survival rate and the character of the lymphoid stroma at the infiltrative margin. Shiozaki et al. (14) reported that the relative 5-year survival rate was 57.3% for cases with high lymphoid stroma and 34.3% for those with low lymphoid stroma at the infiltrative margin.

Recently, cases of GCLS have been reported in association with the Epstein-Barr virus (EBV) (13,15). EBV is associated with lymphoproliferative disorders and also some carcinomas, e.g. nasopharyngeal carcinoma. However, the exact etiological role of EBV in GCLS is uncertain. We analyzed the specimen from our case using the polymerase chain reaction (PCR) technique and found that it was EBV sequence negative.

In conclusion, we have reported a rare case of undifferentiated carcinoma (non-small cell type) with lymphoid infiltration of the esophagus. In most cases, undifferentiated carcinoma of the esophagus generally results in a poor prognosis and usually is not associated with lymphoid infiltration. Thus the prognosis for `undifferentiated carcinoma with lymphoid infiltration' is uncertain, since on the one hand cases of undifferentiated carcinoma have a poor prognosis and on the other cases of carcinoma with lymphoid infiltration have a good prognosis. Further studies on additional cases will be required to clarify the clinical and pathological significance of this rare tumor in the esophagus.

References

1. Moore OS, Foote FW. The relatively favorable prognosis of medullary carcinoma of the breast. Cancer 1949;2:635-42.

2. Hamazaki M, Sawayama K, Kuriya T. Stomach cancer with lymphoid stroma. Saibokakubyourigaku Zasshi 1968;12:115-20 (in Japanese).

3. Ide H, Endo M. Clinical Pathology of Esophageal Tumor. Tokyo: Igaku-Shoin 1984;46.

4. International Union Against Cancer. TNM Classification of Malignant Tumours, 5th ed. 1997.

5. Steiner PE, Maimon SN, Palmer WL, Kirsner JB. Gastric cancer - morphologic factors in five-year survival after gastrectomy. Am J Pathol 1948;24:947-61.

6. Watanabe H, Enjoji M, Imai T. Gastric carcinoma with lymphoid stroma. Cancer 1976;38:232-43. MEDLINE Abstract

7. Shanmugaratnam K, Chan S H, de-The G, Goh J E H, Khor T H, Simons M J, et al. Histopathology of nasopharyngeal carcinoma. Cancer 1979;44:1029-44. MEDLINE Abstract

8. Amano H, Funabiki T, Ochiai M, Sugiue K, Fujita S, Kamei K, et al. A case of histoimmunochemically CEA positive early esophageal carcinoma accompanied by lymphreticular infiltration. Gastroenterol Endosc. 1988;30:395-400 (in Japanese).

9. Mori M, Matsuda H, Kuwano H, Matsuura H, Sugimachi K, et al. Oesophageal squamous cell carcinoma with lymphoid stroma. Virchows Arch A Pathol Anat. 1989;415:473-9.

10. Mizutani K, Makuuchi H, Machimura T, Sugihara T, Sou Y, Shimada H, et al. Medullary carcinoma with lymphoid infiltration of the esophagus. Nippon Syoukakigeka Gakkai Zasshi 1991;24:1033-6 (in Japanese).

11. Morimoto T, Itabashi M, Hirota T, Watanabe H, Kato H, Tachimori Y, et al. Esophageal undifferentiated carcinoma with lymphoid stroma. Nippon Syoukakigeka Gakkai Zasshi 1993;26:859-63 (in Japanese).

12. Kanki K, Yoshizumi Y, Morisaki Y, Sugiura Y, Tamai S, Aida S, et al. Undifferentiated carcinoma with lymphoid stroma of the esophagus. Nippon Syoukakigeka Gakkai Zasshi 1997;30:754-8 (in Japanese).

13. Nakamura S, Ueki T, Yao T, Ueyama T, Tsuneyoshi M. Epstein-Barr virus in gastric carcinoma with lymphoid stroma. Cancer 1994;73:2239-49. MEDLINE Abstract

14. Shiozaki H, Mizunoya S, Okagawa K, Ueno K, Han S, Kobayashi K, et al. Significance of lymphoid stroma at the infiltrative margin on esophageal cancer. Nippon Syoukakigeka Gakkai Zasshi 1983;16:1615-21 (in Japanese).

15. Min KW, Holmquist S, Peiper SC, O'Leary TJ. Poorly differentiated adenocarcinoma with lymphoid stroma (lymphoepithelioma-like carcinomas) of the stomach. Am J Clin Pathol. 1991;96:219-27. MEDLINE Abstract

Received March 1, 1999; accepted July 12, 1999
For reprints and all correspondence: Katsuhiko Shimizu, present address Department of Surgical Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, 1-2-3, Kasumi, Minami-ku, Hiroshima 734-8553, Japan

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Last modification: 1 Dec 1999
Copyright© 1999 Foundation for Promotion of Cancer Research.
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