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Case study

For citation purposes: Park CY, Lee KE, Lim SJ, Kim HJ. Spontaneous regression of recurred adenoid cystic carcinoma in the nasal cavity. Head Neck Oncol. 2012 Sep 9;4(2):48.

Copyright © 2012 OA Publishing London

AbstractAdenoid cystic carcinoma is an epi­thelial tumour of the major and mi­nor salivary glands, accounting for about 1% of all malignant tumours of the oral and maxillofacial region. Sur­gical excision with wide margins is the treatment of choice for adenoid cystic carcinoma, but the tendency of this tumour to locally recur and to de­velop distant metastasis is correlated with an ultimately poor prognosis. Spontaneous regression of cancer, especially in the sinonasal tract, is a rare biological event. Here, we pres­ent a case of recurred adenoid cystic carcinoma of the nasal cavity that spontaneously regressed after an in­tranasal biopsy. We also present a brief literature review.

IntroductionSpontaneous regression (SR) of a ma­lignant tumour is defined as partial or complete disappearance of a tumour in the absence of any treatment or during therapy that does not exert a significant effect on neoplastic dis­ease1,2. SR is known to be very rare, with an estimated incidence of >1 in 60,000–100,000 cases3. The mecha­nisms underlying SR of cancer have not yet been fully determined; how­ever immunologic action, elimination of carcinogens, hormones, trauma, diet and medication have been re­ported as possible causes4. Among the reported cases of SR of cancer, more than half are related to renal cell cancer, neuroblastoma, malignant melanoma and choriocarcinoma5.

Spontaneous regression of recurred adenoid cystic carcinoma in the nasal cavity

CY Park, KE Lee, SJ Lim, HJ Kim*

Adenoid cystic carcinoma (ACC) is the most frequent malignant tumour of the submandibular and minor sali­vary glands, constituting 10% of sali­vary neoplasms, but it is an uncommon malignancy in the sino­nasal tract6,7. ACC in the sinonasal tract tends to be extensively involved in surrounding structures, including the brain, orbit or carotid artery, and it has a moderate to high­risk of local recurrences7. In addition, there is a propensity for discreet regions of tu­mour infiltration along the cranial nerves. These findings make the clin­ical course of ACC potentially morbid. Because ACC in the sinonasal tract is uncommon, it is difficult to define the characteristics, but there are a few reported cases of SR of sinonasal tract ACC where the patient did not receive any type of therapy8. In this study, we present a case of recurred ACC that spontaneously re­gressed after a biopsy was performed to confirm the pathologic diagnosis without treatment. We also present a literature review on SR of ACC in the nasal cavity.

Case presentationIn October 2011, a 74­year­old woman was admitted to our department due to complaints of frequent nasal bleed­ing over a three­month period. The patient had been diagnosed with ACC (pT4aN0M0) of the hard palate in 2006 and had undergone total maxil­lectomy. She also received adjuvant radiotherapy (7000 cGy) to prevent recurrence and she received regular follow-up for five years without any signs of recurrence. Upon physical ex­amination, there was a 1 × 2 cm-sized haemorrhagic mass on the medial portion of the right middle turbinate, which extended from the sphenoid

sinus antrum and tended to bleed easily (Figure 1a). Enhanced perineu­ral spread magnetic resonance imag­ing (PNS MRI) was performed, which revealed a well-defined heteroge­neous enhancing mass between the right middle turbinate and nasal sep­tum (Figure 1b). Therefore, we sus­pected the recurrence of ACC in the nasal cavity and recommended an in­tranasal biopsy for pathologic diag­nosis and further treatment.

Intranasal biopsy using straight cup forceps was performed (Figure 2) under local anaesthesia, which estab­lished the histological diagnosis of recurred ACC (rT1N0M0) of the right nasal cavity (Figures 3a and 3b). Consid ering the patient’s general weakness, booster radiotherapy was planned and it was scheduled to start after one month.

The following month, physical examination of the patient’s nasal cavity was remarkable. The size of the mass was clearly reduced with­out the administration of any kind of treatment and nasal bleeding was not noted. Thus, radiotherapy was delayed and we decided to closely observe the changes in tumour size at our outpatient clinic. Follow­up MRI was performed at two months after biopsy, which indicated that the mass had completely regressed (Figure 4a). At six months after bi­opsy, an intranasal endoscopy showed a barely visible mass lesion in the pa­tient’s nasal cavity (Figure 4b). Since then, the patient has remained in good health and currently shows no signs of recurrence.

Discussion and conclusionACC usually originates in the major or the minor salivary gland of the head and neck6. Although uncommon,

* Corresponding author Email: hyunjk@cau.ac.kr

Department of Otolaryngology–Head and Neck Surgery, Chung­Ang University College of Medicine, Seoul, Korea

For citation purposes: Park CY, Lee KE, Lim SJ, Kim HJ. Spontaneous regression of recurred adenoid cystic carcinoma in the nasal cavity. Head Neck Oncol. 2012 Sep 9;4(2):48.

Copyright © 2012 OA Publishing London

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it has also been reported to develop in the breast, lacrimal gland of the eye, lung, brain, trachea and parana­sal sinuses. ACC is very slow­growing, but has aggressive char acteristics. It spreads to the surrounding tissue, and tends to keep recurring even with repeated and wide resections6. Typical perineural invasion causes pain and invasion along the cranial nerve. Regional lymph node invasion is frequent and distant metastases can occur early6,7. Reports show a survival rate of 89% at five years, but this is dramatically reduced to only 40% at 15 years. Radiotherapy may induce temporary regression, but does not cure the disease and chemo­therapy is not known to be effective either7,8. In the present case, a newly developed ACC around the antrum of the sphenoid sinus occurred five years later, although ACC on the hard palate was completely cured through sur gical resection and post­operative radiotherapy.

SR is defined as the complete disap-pearance of malignant disease with­out medical treatment1,2. Everson and Cole reviewed 176 cases show­ing SR of malignant tumours and determined that the incidence of SR was only 1 in 60,000–100,000 cases3. Of 176 cases of SR of cancer, renal cell carcinoma (RCC) was the most common malignancy and the major­ity involved regression of pulmonary metastases3. The regression of me­tastasis can occur after the removal of the primary tumour, such as nephrectomy in the case of RCC or hysterectomy in the case of choriocarcinomas. Few studies have reported SR of primary malignan­cies, and only five cases of SR of pri­mary thoracic lesion have been reviewed8. SR of primary malignan­cies in the sinonasal tract is rare and few cases of SR of ACC have been re­ported. To the best of our knowledge, our patient is the first case of SR of ACC.

The reason for SR of cancer re­mains unclear. One hypothesis is that

Figure 2: Endoscopy showing an intra­nasal biopsy using straight cup forceps. A histological diagnosis of ACC was established from tissue obtained by intranasal biopsy. *, middle turbinate; #, nasal septum.

(a) (b)

Figure 3: Pathologic results in the present case. (a) Low­power view of the mass showing a solid lesion with variably sized, compact glandular and acinar struc­tures (H & E, ×40). (b) High­power view of the mass showing numerous small monotonous cells with gland formation, characterised by a cribriform pattern (H & E, ×100).

(a) (b)

Figure 1: (a) Pre-treated endoscopic finding in the present case. Intranasal endoscope showed a 1 × 2 cm-sized haemorrhagic mass (white arrow) on the medial portion of the right middle turbinate extending to the sphenoid sinus antrum. (b) Pre­treated perineural spread magnetic resonance imaging (PNS MRI) findings in the present case. The axial view of enhanced T2-weighted PNS MRI shows a well-defined heterogeneous enhancing mass lesion (white arrow) between the upper part of the middle turbinate and the nasal septum. *, middle turbinate; #, nasal septum.

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For citation purposes: Park CY, Lee KE, Lim SJ, Kim HJ. Spontaneous regression of recurred adenoid cystic carcinoma in the nasal cavity. Head Neck Oncol. 2012 Sep 9;4(2):48.

Copyright © 2012 OA Publishing London

Case study

ACC is known to be a highly inva­sive malignancy with a typically fatal prognosis. It is also difficult to achieve adequate locoregional control with ACC. In this report, we presented a case of ACC with SR in the sinonasal tract and suggested that surgical trauma may have been the cause of improvement in the clinical progno­sis of ACC in our patient.

Abbreviations listACC, adenoid cystic carcinoma; MRI, magnetic resonance imaging; PNS, perineural spread; PSN, paraneoplas­tic sensory neuronopathy; RCC, renal cell carcinoma; SR, spontaneous regression.

References1. Stewart FW. Experiences in spontane­ous regression of neoplastic disease in man. Tex Rep Biol Med. 1952;10(1): 239–53. 2. Everson TC, Cole WH. Spontaneous regression of malignant disease. J Am Med Assoc. 1959 Apr;169(15):1758–9. 3. Cole WH. Efforts to explain spontane­ous regression of cancer. J Surg Oncol. 1981;17(3):201–9. 4. Parsons FM, Edwards GF, Anderson CK, Ahmad S, Clark PB, Hetherington C, et al. Regression of malignant tumours in mag­nesium and potassium depletion induced by diet and haemodialysis. Lancet. 1974 Feb;1(7851):243–4. 5. Cole WH. Relationship of causative fac­tors in spontaneous regression of cancer to immunologic factors possibly effective in cancer. J Surg Oncol. 1976;8(5): 391–411. 6. Fordice J, Kershaw C, El­Naggar A, Goepfert H. Adenoid cystic carcinoma of the head and neck: predictors of morbid­ity and mortality. Arch Otolaryngol Head Neck Surg. 1999 Feb;125(2): 149–52. 7. Gondivkar SM, Gadbail AR, Chole R, Parikh RV. Adenoid cystic carcinoma: a rare clinical entity and literature review. Oral Oncol. 2011 Apr;47(4):231–6. 8. Grillet B, Demedts M, Roelens J, Goddeeris P, Fossion E. Spontaneous re­gression of lung metastases of adenoid cystic carcinoma. Chest. 1984 Feb;85(2): 289–91.

therapy and immune deficiency syn­dromes, through the use of biological modulators, or during infection or hormonal changes. In particular, surgical trauma may also induce im­mune dysfunction of tumour cells, thereby resulting in direct necrosis and SR in patients9,12.

In the case of thoracic malignan­cies, surgical trauma had also been reported to result in SR13–16. Interestingly, 43% of thoracic malig­nancies that regressed spontane­ously were observed in patients who had received surgical trauma3,15. In those cases, surgical trauma included procedures such as bronchoscopy and incomplete tumour removal. As for the patient in our case, an intrana­sal biopsy was performed for a patho­logic diagnosis and the recurred ACC regressed without additional treatment one month after the bi­opsy. We did not find any clinical or physical signs of neurologic toxicity to confirm PSN but estimated that surgical trauma to recurred ACC may have potentially acted as a trig­ger for an immune response, result­ing in SR.

tumours may sometimes grow more rapidly than their blood supply, which may cause direct necrosis and regression of the tumours. However, the definite causes for such a rapid growth of tumour cells have not yet been verified9.

Paraneoplastic sensory neuronop­athy (PSN), which is a rare syndrome causing sensory ataxia in the distal extremities, has been suggested as a cause of SR of small­cell lung cancer in some patients10. It has been re­ported that specific autoantibodies such as anti­Hu, anti­Yo and anti­Ri antibodies react with tumour tissues, resulting in the activation of the T lymphocyte immune response11. Although neurologic toxicity is a con­cern, patients with these autoanti­bodies tend to have a better cancer prognosis, with the tumour being smaller, less metastatic and more slow growing11.

Recent reports have focused on al­teration of the immune system such as T­cell and/or B­cell dysfunction as an explanation for SR, which has been observed in a variety of clinical set­tings such as in immune suppressive

(a) (b)

Figure 4: (a) Perineural spread magnetic resonance imaging (PNS MRI) find­ings after an intranasal biopsy. PNS MRI was performed at two months after the intranasal biopsy. The enhanced T2­weighted axial view showed that the previ­ous mass lesion on the medial portion of the middle turbinate had disappeared and no suspected malignant lesion was observed. (b) Endoscopic finding after an intranasal biopsy. Endoscopic examination was performed at six months af­ter the intranasal biopsy and healthy nasal mucosa was observed around the middle turbinate and the nasal septum. No tumour­like lesion was detected. *, middle turbinate; #, nasal septum.

For citation purposes: Park CY, Lee KE, Lim SJ, Kim HJ. Spontaneous regression of recurred adenoid cystic carcinoma in the nasal cavity. Head Neck Oncol. 2012 Sep 9;4(2):48.

Copyright © 2012 OA Publishing London

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with scalene node metastasis. Cancer. 1986 Aug;58(4):978–80. 15. Zaheer W, Friedland ML, Cooper EB, DoRosario A, Burd RM, Gagliardi J, et al. Spontaneous regression of small cell carci­noma of lung associated with severe neu­ropathy. Cancer Invest. 1993;11(3):306–9. 16. Nomura M, Fujimura M, Matsuda T, Nonomura A, Kitagawa M, Nakamura H, et al. [Spontaneous regression of small cell lung cancer]. Nihon Kyobu Shikkan Gakkai Zasshi. 1994 Apr;32(4):324–7.

with paraneoplastic neuronal antibodies. Lancet. 1993 Jan;341(8836):21–2. 12. Tanaka K, Tanaka M, Inuzuka T, Nakano R, Tsuji S. Cytotoxic T lymphocyte­mediated cell death in paraneoplastic sen­sory neuronopathy with anti­Hu antibody. J Neurol Sci. 1999 Mar;163(2):159–62. 13. Smith RA. Cure of lung cancer from incomplete surgical resection. Br Med J. 1971 Jun;2(5761):563–5. 14. Lowy AD Jr, Erickson ER. Spontaneous 19­year regression of oat cell carcinoma

9. Montie JE, Straffon RA, Deodhar SD, Barna B. In vitro assessment of cell­ mediated immunity in patients with renal cell carcinoma. J Urol 1976 Mar;115(3): 239–42.10. Samellas W, Marks AR. Apparent spontaneous regression of pulmonary metastases following nephrectomy for adenocarcinoma of the kidney. J Urol. 1961 Apr;85:494–6. 11. Darnell RB, DeAngelis LM. Regres sion of small­cell lung carcinoma in patients