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Adenoid cystic carcinoma with high-grade transformation

2023; Elsevier BV; Linguagem: Inglês

10.1016/j.pathol.2023.06.012

1465-3931

Yan Xia, Xianglei He,

Oral and Maxillofacial Pathology

Adenoid cystic carcinoma (AdCC) is a common malignant tumour of the salivary gland characterised clinically by slow progression but a high rate of recurrence and metastasis. AdCC consists of two types of cells, ductal epithelial cells and myoepithelial cells, with three main growth patterns: tubular, sieve and solid.1Stennman G. Licitra L. Said-AI-Naief N. et al.Adenoid cystic carcinoma.in: El-Naggar A.K. Chan J.K. Grandis J.R. WHO Classification of Head and Neck Tumours. 4th ed. IARC Press, Lyon2017: 164-165Google Scholar The occurrence of high-grade transformation (HGT) in AdCC is a rare phenomenon, with the high-grade component most often showing hypodifferentiated adenocarcinoma or undifferentiated carcinoma, with histological features including loss of the biphasic pattern and typical histopathological features of malignancy, such as marked cellular atypia, increased proliferative activity and necrosis. It is considered a highly aggressive tumour because of its high recurrence rate and risk of metastasis and poor prognosis.2Seethala R.R. Hunt J.L. Baloch Z.W. et al.Adenoid cystic carcinoma with high-grade transformation: a report of 11 cases and a review of the literature.Am J Surg Pathol. 2007; 31: 1683-1694Crossref PubMed Scopus (192) Google Scholar Here, we report a rare case of adenoid cystic carcinoma with high-grade transformation (AdCC-HGT). An 80-year-old female presented with a swelling on the right side of her tongue that was self-reported more than 10 years previously and had increased in size over the past year. Enhanced computed tomography (CT) of the head and neck revealed a slightly dense shadow in the tip of the tongue, which showed significant enhancement. A small biopsy was performed in another hospital and the result was reported to be a malignant tumour of minor salivary gland origin with a tendency to pleomorphic adenocarcinoma. The patient underwent partial resection of tongue tumour and cervical lymph node dissection. An intraoperative cauliflower-like mass of about 2.5×1.5 cm in size, hard and poorly defined, without involvement of the floor of the mouth, was seen on the right side of the tongue. The surgical specimen sent for examination was a piece of grey-red irregular tissue measuring 3.3×2.5×2.3 cm, and a greyish-white nodule measuring 2.0×1.0×0.7 cm, with moderate solidity and still-clear borders, which were visible on the cut surface. After haematoxylin-eosin staining, the tumour was seen to consist of two parts under the microscope (Fig. 1A). In one part, the tumour cells consisted of luminal surface cells and myoepithelial cells, arranged in small clusters and stripes, with small foci in the shape of sieves. Basophilic mucus was seen in the pseudocapsular cavity, with abundant extracellular matrix, and glassy interstitial fibres which squeezed the tumour cells into a bundle-like striped arrangement (Fig. 1B). In the other part, the tumour was arranged in a large solid nest-like pattern, with lamellar necrosis seen in the centre of the nest. Compared with the former, the tumour cells were clearly heterogeneous, with large, vacuolated nuclei, obvious nucleoli, visible nuclear schizophrenia, and reduced or absent myoepithelium (Fig. 1C). A zone of gradual transition existed between these two areas. The tumour invaded the nerves, and tumour metastases were visible in the lymph nodes (Fig. 1D). Immunohistochemical staining showed myoepithelial expression of p63, p40, S100 and calponin in a portion of the tumour area (Fig. 2A,B), p53 variable strong positive expression in 40% of the tumour cells (Fig. 2C), and Ki-67 positivity in about 40% (Fig. 2D). In the other part, no myoepithelium was seen (Fig. 2A,B), p53 showed strong positive expression in 80% of tumour cells in a diffuse and consistent manner (Fig. 2C), and Ki-67 was positive in about 85% (Fig. 2D). Fluorescence in situ hybridisation (FISH) assay revealed a break in the MYB gene. The final diagnosis was AdCC-HGT, infiltrating into the transverse muscle, positive for nerve involvement, negative for vascular involvement, negative for cut margins, and cancer metastasis visible in lymph nodes (7/19). This case was treated with radiation therapy three times after surgical resection and followed up for 18 months, with no recurrence or metastasis in survival to date. More than 60 cases of AdCC-HGT have been reported in the literature2Seethala R.R. Hunt J.L. Baloch Z.W. et al.Adenoid cystic carcinoma with high-grade transformation: a report of 11 cases and a review of the literature.Am J Surg Pathol. 2007; 31: 1683-1694Crossref PubMed Scopus (192) Google Scholar, 3Cheuk W. Chan J.K. Ngan R.K. Dedifferentiation in adenoid cystic carcinoma of salivary gland: an uncommon complication associated with an accelerated clinical course.Am J Surg Pathol. 1999; 23: 465-472Crossref PubMed Scopus (126) Google Scholar, 4Hellquist H. Skálová A. Barnes L. et al.Cervical lymph node metastasis in high-grade transformation of head and neck adenoid cystic carcinoma: a collective international review.Adv Ther. 2016; 33: 357-368Crossref PubMed Scopus (51) Google Scholar, 5Tando S. Nagao T. Kayano K. et al.High-grade transformation/dedifferentiation of an adenoid cystic carcinoma of the minor salivary gland to myoepithelial carcinoma.Pathol Int. 2018; 68: 133-138Crossref PubMed Scopus (9) Google Scholar, 6Miyazaki M. Aoki M. Koga K. et al.Adenoid cystic carcinoma with high-grade transformation forming spindle cell component of the submandibular gland.Auris Nasus Larynx. 2019; 46: 934-939Abstract Full Text Full Text PDF PubMed Google Scholar, 7Chia N. Petersson F. Adenoid cystic carcinoma with dedifferentiation/expansion of the luminal cell component and preserved biphasic morphology - early high-grade transformation.Ann Diagn Pathol. 2021; 50151650Crossref PubMed Scopus (5) Google Scholar since Cheuk et al. first described the ‘dedifferentiation’ of AdCC in 1999,3Cheuk W. Chan J.K. Ngan R.K. Dedifferentiation in adenoid cystic carcinoma of salivary gland: an uncommon complication associated with an accelerated clinical course.Am J Surg Pathol. 1999; 23: 465-472Crossref PubMed Scopus (126) Google Scholar followed by Seethala et al. who first systematically described the pathological features of high-grade transformation and generalised the diagnostic criteria for high-grade transformation of AdCC.2Seethala R.R. Hunt J.L. Baloch Z.W. et al.Adenoid cystic carcinoma with high-grade transformation: a report of 11 cases and a review of the literature.Am J Surg Pathol. 2007; 31: 1683-1694Crossref PubMed Scopus (192) Google Scholar In this case, the fibrous interstitium was sclerotic and most of the solid AdCC areas were extruded in a striated pattern. This case was mistakenly thought to be a ‘polymorphic adenocarcinoma’ (PAC) by another hospital before immunohistochemical staining, due to the limited biopsy of small specimens. PAC tumors are structurally diverse, trabecular and sieve-like are common, and sometimes have a morphology similar to that of AdCC, but the swirling, target-ring-like arrangement of the peripheral borders of the tumors is the characteristic structure.8Fonseca I. Assaad A. Katabi N. et al.Polymorphous adenocarcinoma.in: El-Naggar A.K. Chan J.K. Grandis J.R. WHO Classification of Head and Neck Tumours. 4th ed. IARC Press, Lyon2017: 167-168Google Scholar Moreover, AdCC ducts are composed of bilayer cells and immunohistochemical staining is positive for both p63 and p40, whereas PAC is positive for p63 and often negative for p40,1Stennman G. Licitra L. Said-AI-Naief N. et al.Adenoid cystic carcinoma.in: El-Naggar A.K. Chan J.K. Grandis J.R. WHO Classification of Head and Neck Tumours. 4th ed. IARC Press, Lyon2017: 164-165Google Scholar,8Fonseca I. Assaad A. Katabi N. et al.Polymorphous adenocarcinoma.in: El-Naggar A.K. Chan J.K. Grandis J.R. WHO Classification of Head and Neck Tumours. 4th ed. IARC Press, Lyon2017: 167-168Google Scholar which will help to differentiate the two. It should be noted that the high-grade transformation zone of AdCC-HGT needs to be distinguished from solid type AdCC. In this case, the tumour cells in the high-grade transformation zone had significantly increased heterogeneity and more nuclear divisions, necrosis was seen in the centre of the tumour nest, and immunohistochemistry could confirm the features of adenocarcinoma such as loss of myoepithelium and elevated Ki-67, all of which helped to confirm the high-grade transformation. Similar to a case reported by Tando et al.,5Tando S. Nagao T. Kayano K. et al.High-grade transformation/dedifferentiation of an adenoid cystic carcinoma of the minor salivary gland to myoepithelial carcinoma.Pathol Int. 2018; 68: 133-138Crossref PubMed Scopus (9) Google Scholar our case also had a typical transition zone between the conventional and highly malignant tumour components, suggesting the same origin and a possible manifestation of malignant progression. By immunohistochemical staining, p53 showed wild-type in the conventional AdCC region and missense mutant in the HGT region. Due to the small number of cases, there are not many studies on the mechanisms of molecular biological alterations in AdCC-HGT, and some molecular studies have reported TP53 mutations and overexpression of p53 protein in high-grade components,9Chau Y. Hongyo T. Aozasa K. et al.Dedifferentiation of adenoid cystic carcinoma: report of a case implicating p53 gene mutation.Hum Pathol. 2001; 32: 1403-1407Crossref PubMed Scopus (70) Google Scholar,10Seethala R.R. Cieply K. Barnes E.L. et al.Progressive genetic alterations of adenoid cystic carcinoma with high-grade transformation.Arch Pathol Lab Med. 2011; 135: 123-130Crossref PubMed Google Scholar suggesting that p53 abnormalities may play a major role in the development of AdCC-HGT. A break in the MYB gene was found in this case by FISH, whereas alterations in the MYB gene were rare in previous reports on AdCC-HGT. Chromosomal translocation of MYB, which is considered an early and major oncogenic factor in AdCC, and this event occurs in approximately one-third of AdCC.11Mitani Y. Li J. Rao P.H. et al.Comprehensive analysis of the MYB-NFIB gene fusion in salivary adenoid cystic carcinoma: incidence, variability, and clinicopathologic significance.Clin Cancer Res. 2010; 16: 4722-4731Crossref PubMed Scopus (237) Google Scholar Although the study of MYB in AdCC by Costa et al. showed unique genetic alterations in both conventional and transformed components,12Costa A.F. Altemani A. García-Inclán C. et al.Analysis of MYB oncogene in transformed adenoid cystic carcinomas reveals distinct pathways of tumor progression.Lab Invest. 2014; 94: 692-702Abstract Full Text Full Text PDF PubMed Scopus (24) Google Scholar the presence of alterations in the MYB gene in clinical cases still contributes to the diagnosis of AdCC-HGT. Similar to conventional AdCC, nerve invasion is common in the HGT region, but AdCC-HGT usually results in metastasis to the cervical lymph nodes in about half of cases, which is 5–10 times more common than conventional types of AdCC.4Hellquist H. Skálová A. Barnes L. et al.Cervical lymph node metastasis in high-grade transformation of head and neck adenoid cystic carcinoma: a collective international review.Adv Ther. 2016; 33: 357-368Crossref PubMed Scopus (51) Google Scholar In this case, in addition to nerve invasion, metastatic carcinoma was found in nearly half of the cervical lymph nodes, and most of them had a high-grade transformed form. Due to the high proliferative activity and lymph node metastasis rate, three radiation treatments were performed after surgical resection and regional lymph node dissection in this case. After 18 months of follow-up we have not seen tumour recurrence or metastasis, although the median survival time for AdCC-HGT is 36 months as shown through previous case reports.2Seethala R.R. Hunt J.L. Baloch Z.W. et al.Adenoid cystic carcinoma with high-grade transformation: a report of 11 cases and a review of the literature.Am J Surg Pathol. 2007; 31: 1683-1694Crossref PubMed Scopus (192) Google Scholar In conclusion, AdCC-HGT is a relatively rare and more malignant phenomenon, which should not be missed by misdiagnosing the transformed area as solid type, and sometimes needs to be differentiated from PAC, where high-grade transformation is more common. It is helpful for the diagnosis of AdCC-HGT if immunohistochemical staining shows myoepithelial deletion and molecular detection shows MYB mutation. The authors state that there are no conflicts of interest or sources of funding to disclose.