- Research into the oncogenesis of adenoid cystic carcinoma has revealed a low prevalence of mutations in common oncogenes and tumor-suppressor genes (Stephens 2013).
- A genetic translocation t(6;9)(q22-23;p23-24) has been identified in adenoid cystic carcinoma of the breast and head and neck (Persson 2012) that results in a v‑myb avian myeloblastosis viral oncogene homolog-nuclear factor I/B (MYB‑NFIB) gene fusion oncoprotein (Persson 2009).
- The MYB‑NFIB oncoprotein is overexpressed in more than 85% of adenoid cystic carcinomas at nonlacrimal sites (Brill 2011).
- The MYB‑NFIB fusion gene was found in 7 of 14 lacrimal gland adenoid cystic carcinomas (ACC) studied and none of 19 non-ACC lacrimal gland tumors (Von Holstein 2013).
- High nuclear expression of MYB RNA was found in 2 lacrimal gland ACCs studied; 3 of the lacrimal gland ACCs without MYB‑NFIB fusion had other forms of MYB rearrangement; and all 13 lacrimal ACCs studied had high nuclear expression of the MYB oncogene. RNA and oncoprotein expression remain to be demonstrated more definitively.
- The MYB oncoprotein targets cell growth, apoptosis, transcriptional regulation, and cell cycle control. In the study cited above of 14 lacrimal gland ACCs there was no correlation between patient survival and MYB-NFIB status. It is present in the tumor, but its precise role is not known (Persson 2012).
- The most common malignant epithelial tumor of the lacrimal gland
- Accounts for 10–15% of epithelial lacrimal gland neoplasms
- Adenoid cystic carcinoma of the lacrimal gland accounts for 5–10% of all adenoid cystic carcinomas.
- Adenoid cystic carcinoma accounts for only 1% of head and neck malignancies.
- Less malignant course in children
- No apparent sex predilection
- The clinical history helps differentiate between adenoid cystic carcinoma and benign lacrimal gland tumors such as pleomorphic adenoma.
- Pain might be present — would not be typical of a benign tumor.
- Progressive (signs and symptoms present < 1 year) — benign tumors also grow, but more slowly.
- Paresthesias (perineural invasion) would be unusual with a benign tumor, except with long-term compression.
- Ptosis, especially temporally — mass effect can be seen with pleomorphic adenoma, but more pronounced with ACC.
- Proptosis, axial and inferior and medial globe displacement of globe (Figures 1 and 2)
- Motility disturbance
Figure 1. Adenoid cystic carcinoma. Courtesy Evan H. Black, MD.
Figure 2. Adenoid cystic carcinoma. Courtesy Raymond Cho, MD.
- Computed tomography (CT) scan
- Lacrimal fossa mass with bony erosion — typically irregular bony destruction
- Possible apical extension into the superior orbital fissure
- Less well circumscribed lesion than benign mixed tumor
- Magnetic resonance imaging (MRI) scan is useful to define posterior extension of the lesion further (Figure 3)
- Pathology — lesion is nonencapsulated and infiltrating, indicating need for incisional biopsy (Figure 4).
- Histologically, adenoid cystic carcinomas are subtyped into tubular, cribriform, or basaloid growth patterns (solid). Most show mixed histology.
- Basaloid variant has more aggressive biologic behavior and is associated with overall shorter survival.
- Bone invasion is frequently (about 75%) evident on initial staging.
Figure 3. MRI of adenoid cystic carcinoma. Courtesy Raymond Cho, MD.
Figure 4. Adenoid cystic carcinoma slide. Courtesy Raymond Cho, MD.
Testing for staging, fundamental impairment
Staging — 6th edition American Joint Committee on Cancer (AJCC) TNM definitions for carcinoma of the lacrimal gland:
- Tx Primary tumor cannot be assessed.
- T0 No evidence of primary tumor
- T1 Tumor ≤ 2.5 cm in greatest dimension limited to the lacrimal gland
- T2 Tumor ≤ 2.5 cm in greatest dimension invading the periosteum of the fossa of the lacrimal gland
- T3 Tumor between 2.5 and 5 cm in greatest dimension (T3a limited to the lacrimal gland, T3b invades the periosteum.)
- T4 Tumor > 5 cm in greatest dimension (T4a invades the orbital soft tissue, optic nerve, or globe without bone invasion. T4b invades the orbital soft tissue, optic nerve, or globe with bone invasion.)
- NX Regional lymph nodes cannot be assessed
- N0 No regional lymph node metastasis
- N1 Regional lymph node metastasis
- Mx Distant metastasis cannot be assessed
- M0 No distant metastasis
- M1 Distant metastasis
AJCC seventh edition:
- In the sixth edition, small tumors (< 2.5 cm — T1 versus T2) and medium tumors (2.5–5‑cm — T3a versus T3b) were classified depending on whether they have invaded through the periostium to local bone;
- Large tumors (> 5 cm) were most likely to be T4b with bone invasion
- In the seventh edition, tumors of any size with bone or periosteal involvement are classified as T4. Separation in this newer classification system is based on size.
- T1 = tumor 2 cm or smaller
- T2 = tumor 2–4 cm in size
- T3 = tumor greater than 4 cm
- T4 = bone or periosteal invasion
- T4a = periosteal invasion
- T4b = bone invasion
- T4c = invasion of adjacent structures including brain and sinuses
Frequent staging patterns:
- Staging helps predict outcome; in a recent review of 53 patients, using the 6th edition classification, 38 (72%) had > T3 tumors at presentation (Ahmad 2009).
- In that series, seventeen (45%) of the 38 patients with > T3 tumors and only 1 (7%) of the 15 patients with < T3 tumors died of disease during the study period, during median follow-up of 94 months (7.9 years; 95% confidence interval, 50–120 months) (Ahmad 2009).
- Nodal metastasis is less frequent with this tumor; invasion is most commonly intracranial and of the adjoining bone (Von Holstein 2013).
- Distant metastasis is not commonly recognized on initial staging; about 10% of cases (Williams 2010).
Staging was compared using the 6th versus 7th classification system (El-Sawy 2012).
- Because periosteal and bone invasion are so common at presentation with adenoid cystic carcinoma of the lacrimal gland a significant percentage of patients are upstaged when using the seventh vs the sixth edition classification system (5% versus 80% had T4 disease in this study of 18 patients).