Carcinoma of the Esophagus - part 3 pot

Tumors arising 1–5 cm above the junction type 1 are staged with the esophageal TNM, whilst the gastric TNM system is recommended for tumors arising at the junction type 2 or 2–5 cm below

Metaplastic or dysplastic glandular epithelium may persist beneath the new squa-mous epithelium; hence, deep biopsies are required on follow-up Currently, the long-term behavior of this concealed glandular epithelium is unknown

Invasive adenocarcinoma

Macroscopic appearance

Most tumors are advanced at the time of presentation and are ulcerating infiltrative lesions (Figure 2.6) They are less frequently exophytic (10–15%) compared with squamous cell carcinomas [41] Rarely, they appear papillary or show diffuse infiltration resembling gastric linitis plastica [42]

Microscopic appearance

Adenocarcinomas are graded as well, moderately or poorly differentiated, accord-ing to the proportion of tumor cells formaccord-ing glands (Figure 2.7a and b) Tumors can be mucinous with prominent extracellular mucin pools Signet ring cell carcinoma is rare [43] Very rarely, CLE-associated adenocarcinoma may have foci of admixed choriocarcinoma [44,45]

Small cell carcinoma

This accounts for approximately 1% of primary esophageal carcinomas [46] It has a similar appearance to the more common pulmonary tumor and is highly aggressive

Figure 2.7 Invasive adenocarcinoma (a) Well-differentiated adenocarcinoma composed of

infiltrating glands with mild cytological atypia (b) Poorly differentiated adenocarcinoma

composed of sheets of cells without gland formation.

Pathology of Esophageal Cancer 21

The TNM system is used for staging [47] The Siewert classification is recom-mended for adenocarcinoma around the esophagogastric junction [48] Tumors arising 1–5 cm above the junction (type 1) are staged with the esophageal TNM, whilst the gastric TNM system is recommended for tumors arising at the junction (type 2) or 2–5 cm below (type 3) Proformas have been developed to ensure that all relevant prognostic information is included in pathology reports [49,50]

Prognostic factors

Depth of tumor invasion is the most important and often the only independent prognostic indicator on multivariate analysis [41,51,52] Lymph node metastasis is also a significant prognostic factor The number of positive nodes and ratio of involved to uninvolved nodes have been found to be significant [53,54] Vascular invasion and resection margin status have also been repeatedly shown to be significant on univariate analysis [41,51,55,56,57]

The histological type of tumor has not been shown to be significant in advanced disease, but several studies have shown a survival advantage for early (T1) adeno-carcinoma compared to squamous cell adeno-carcinoma [58,59] Other histological and molecular markers such as tumor grade, p53 and Her2 status, and ploidy do not appear to be independent predictors of poor prognosis [51,52,60,61]

Figure 2.8 Effects of chemoradiotherapy Acellular mucin pools throughout the esophageal wall

in a treated adenocarcinoma.

22 H M R Deere

Neoadjuvant treatment

As a consequence of the increasing use of preoperative chemoradiotherapy, resec-tion specimens may often show the effects of this treatment Systems for scoring the degree of regression exist but are rarely used in routine practice [62,63] With response to therapy, ulceration, inflammation, fibrosis, and calcification are fre-quently seen Sections may show only keratin surrounded by a foreign body giant cell reaction when a squamous cell carcinoma has regressed Mucin pools are frequently seen in treated adenocarcinomas (Figure 2.8) Viable tumor may be present as small groups of cells, and these may show marked atypia due to the treatment Cytokeratin staining is often required when only occasional tumor cells remain Staging is based only on residual viable tumor Tumor that has completely regressed would be staged as ypT0N0

Conclusion

The role of the surgical pathologist has expanded from providing solely diag-nostic information to include some important data regarding prognosis At present this prognostic information is limited to histological factors with regard to esophageal tumors Biological markers are been intensively studied in the research setting, and it

is anticipated that these will be of increasing value in routine practice in determining prognosis and hopefully increase management options for these tumors

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Pathology of Esophageal Cancer 23

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Pathology of Esophageal Cancer 25

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26 H M R Deere

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Pathology of Esophageal Cancer 27

Recent Advances in the Endoscopic Diagnosis

of Esophageal Cancer

Anne Marie Lennon and Ian D Penman

Introduction

Esophageal cancer is the seventh most common malignancy worldwide and has the sixth highest cancer mortality rate [1] It has one of the most rapidly increasing incidence of all cancers in the last 5 years [2,3] and is associated with a poor 1 and 5-year survival in the UK [4]

Correct staging of esophageal cancer is essential for patient care This not only gives a good indication of survival but also allows for optimum management of the patient In patients with very early oesophageal cancer (Tis/T1m), local treatment with endoscopic mucosal resection (EMR) or photodynamic therapy can be considered For those patients with more advanced disease (Stages IIB–III), many centers now advocate using neoadjuvant chemotherapy (OEO2) or chemor-adiotherapy prior to surgery as this may improve survival [5,6] For those patients with metastatic disease (Stage IV), palliative treatment is appropriate

Endoscopic imaging

Flexible videoendoscopy with biopsy and/or brush cytology is the gold standard investigation for the diagnosis of esophageal carcinoma Endoscopy is more sensitive and specific than double-contrast barium meal for the diagnosis of upper gastrointestinal cancer [7], and when biopsy and cytology are combined, the accuracy of endoscopy for diagnosis approaches 100% [8] Rarely, in patients with pseudoachalasia and repeated negative mucosal biopsy, endoscopic ultra-sound with or without fine-needle aspiration biopsy may provide supportive evidence for malignancy and a tissue diagnosis [9]

Carcinoma of the Esophagus, ed Sheila C Rankin Published by Cambridge University Press # Cambridge University Press 2008.

When a suspicious lesion is seen at endoscopy, it is important to document certain features (Table 3.1) that may provide important information for planning therapy and deciding between surgical resection, radiotherapy, and stent insertion Lesions at the esophagogastric junction (EG junction) should be classified using the Siewert classification [10]: those which are predominantly in the esophagus are type 1 junctional; those that are mainly within the stomach are type 3; and those that are equally distributed between the esophagus and stomach as type 2

Early esophageal cancer may appear as minor irregularities of the mucosa, areas of erythema, or depressed, raised, or ulcerated areas (Figure 3.1) Japanese

Table 3.1 Features to note at endoscopy on diagnosis of an esophageal cancer

1 Position relative to the incisor teeth (in centimeters) with proximal and distal margins

2 The morphology of the lesion using the Japanese–Bormann classification (Table 4) if the

lesion is compatible with a superficial lesion

3 Presence and proximal extent of any Barrett’s esophagus

4 Presence of a hiatal hernia

5 Involvement of the gastric cardia or extension along lesser curve

6 Presence of metastatic or synchronous lesions elsewhere in the upper gastrointestinal tract

7 Previous gastric or duodenal surgery

Figure 3.1 (a) Endoscopic view of early squamous carcinoma seen as a raised nodular area with

superficial ulceration (b) Early superficial (5 mm) adenocarcinoma arising in short-segment Barrett’s

esophagus just above the esophagogastric junction.

Recent Advances in the Endoscopic Diagnosis of Esophageal Cancer 29

endoscopists have found that the endoscopic classification of a lesion can be an important determinant of whether endoscopic therapy, such as EMR, should be applied They have attempted to identify this group of patients with minimally invasive disease, using endoscopic features [11] Based on these features, the tumor can be divided into types 0 to 5, where type 0 corresponds with a minimally invasive tumor and type 4 with a diffusely infiltrating cancer (Table 3.2) Type 0 tumors are further subdivided based on their endoscopic appearance into types 0-I, 0-II, and 0-III, with types 0-I and 0-II further sub-divided A detailed description, with illustration of different endoscopic staging features, can be found elsewhere [12]

Dysplasia or early esophageal cancer can be difficult to detect even for an experienced endoscopist This is because lesions are often subtle, presenting as small erosive or flat plaques The use of four-quadrant biopsies in Barrett’s esophagus has a low sensitivity, as high-grade intraepithelial neoplasia (HGIN) and early adenocarcinoma are often multifocal and flat New techniques have therefore been developed, which highlight dysplastic or neoplastic lesions through

a variety of methods

Table 3.2 Classification of superficial esophageal tumors using the Japanese system [12]

Type 0 Superficial polypoid, flat/depressed, or excavated

Type 0-II Nonpolypoid and nonexcavated

Type 0-IIa Slightly elevated

Type 0-IIb Completely flat

Type 0-IIc Slightly depressed without ulcer

Type 0-III Nonpolypoid with a frank ulcer

Type 1 Polypoid, usually attached to a wide base

Type 2 Ulcerated carcinomas with sharply demarcated and raised margins Type 3 Ulcerated, infiltrating carcinomas without definite limits

Type 4 Nonulcerated, diffusely infiltrating carcinomas

30 A M Lennon and I D Penman