Current Challenges in the Staging of Oral Cancer

Abstract

In the recently published 8th edition of the AJCC Cancer Staging Manual, new pathological elements are required for the N and T category determinations for oral cavity cancers. This includes determination of depth of tumor invasion and assessment of metastatic lymph nodes for extranodal extension. Although definitions and some guidance are provided for the interpretation of these elements, pathologists frequently encounter ambiguous situations that may result in interobserver and intraobserver variability. Pre-existing staging elements, such as assessment of bone invasion, can also be problematic to interpret. Difficulties in the interpretation of depth of invasion, bone invasion and extranodal invasion are discussed, with examples. Communication with the surgeon, proper specimen orientation, gross examination and sampling are crucial to assessment of these elements. Liberal use of deeper levels and submission of additional sections is suggested. Although general staging guidelines encourage clinicians and pathologists to choose the lower category when there is ambiguity, pathologists may choose to discuss difficulties in the interpretation of specific cases at interdisciplinary tumor boards, to allow a more informed choice of treatment on the part of treating physician and patient. More discussion is required among pathologists to develop specific guidelines for the interpretation of these staging elements.

Keywords: Lymph nodes; Mouth neoplasms; Neoplasm staging; Observer variation; Prognosis.

Fig. 1

a Whole mount image of a lateral tongue squamous cell carcinoma. A horizontal line from adjacent benign epithelium on each side of this tumor would underestimate tumor depth of invasion (DOI). DOI was measured from the surface of the tumor to the deepest point of invasion (arrow). In effect, an “arcuate” line was created to account for the normal contour of the tongue. b Left side of this tumor as seen in 1a, with adjacent benign epithelium. Even though the tumor is not exophytic, the epithelium is drawn upwards, meeting an ulcer. The raised epithelium is a more appropriate choice as the origin for a “horizon” line (arrow). In this case, the line chosen was arcuate across the tumor surface rather than straight across to the opposite side of the tumor. c Right side of this tumor as seen in 1a. Tumor focally undermines adjacent benign epithelium. Choice of anything other than an arcuate line would be quite subjective and would underestimate DOI. d Desmin-stained slide of the same tumor. Skeletal muscle is drawn close to the surface of the mid-portion of the tumor, further justifying the method of DOI measurement described above

Fig. 2

a Worst pattern of invasion type 5. A nest of tumor is present > 1 mm from the main bulk of the tumor (arrow), with intervening normal tissue. b High power image of separate tumor island. No perineural or lymphovascular origin is identified

Fig. 3

a An exophytic maxillary tumor with erosion of the cortical bone of the edentulous alveolar ridge. No bone invasion is identified at this location. b Same tumor at a different location. The leading edge of the tumor has eroded most of the bone, leaving only a thin layer of cortical bone under the sinus mucosa (arrow). Only a small amount of cancellous bone is visible, on the lower left. c The tumor has destroyed most of the bone, with a leading edge of fibroinflammatory tissue and no direct contact between tumor and bone. This was interpreted as bone invasion (category pT4a), but as only minimal cancellous bone is identified nearby, and there is no direct invasion of tumor into the medullary space, that diagnosis is debatable. d Bone of the maxilla from lower right of the field in 3b. In this edentulous patient, the bone is essentially cortical type

Fig. 4

a Major extranodal extension (ENE), with tumor invading perinodal adipose tissue. The arrow from the capsule to the furthest point of invasion demonstrates how to measure extranodal extension. b Minor extranodal extension with tumor invading adipose tissue with a desmoplastic response. The node capsule is not preserved centrally, nor visualized on the right. An arcuate line has been created to approximate the contour of the node capsule/edge, from which ENE can be measured

Fig. 5

a Lymph node with an incomplete capsule and metastatic carcinoma. Although a subcapsular sinus is seen focally (upper left), in other areas the lymphoid tissue merges with perinodal fat. b A lymph node with a capsular defect and protruding lymphoid tissue. Metastatic carcinoma is seen on the lower right, confined to the node

Fig. 6

a In this lymph node with metastatic carcinoma, there is no capsule surrounding the lymphoid tissue that contains tumor. The hilum of the node is towards the left. The edge of the lymphoid tissue with tumor was in smooth continuity with the rest of the node, and this was not interpreted as ENE. b Same case as 6a, but a different lymph node. Again the capsule is ill-defined and the lymphoid tissue in the upper part of the field could be interpreted as extranodal and reactive. The ill-defined periphery and desmoplastic response to tumor in the upper right was interpreted as microscopic extranodal extension. However, this determination and the site of the “external aspect of the capsule” for ENE measurement are both subjective

Fig. 7

a Metastatic squamous cell carcinoma at the periphery of a lymph node, with a desmoplastic response and tumor admixed with fat, consistent with microscopic extranodal extension. Accurately measuring the extent of ENE is challenging, as the site from which to measure is open to interpretation. b Tumor islands clearly extend into adipose tissue

Fig. 8

Metastatic squamous cell carcinoma with a thickened fibrous “neo-capsule”. This was interpreted as minor ENE as tumor clearly bulges beyond the contour of the periphery of the node