G Model
ANL-1991; No. of Pages 4 Auris Nasus Larynx xxx (2015) xxx–xxx
Contents lists available at ScienceDirect
Auris Nasus Larynx journal homepage: www.elsevier.com/locate/anl
Clear cell carcinoma of the nasal cavity: A case report from histopathological viewpoint Takayuki Imai a,*, Ikuro Satoh b, Ko Matsumoto c, Shigemi Ito b, Yukinori Asada a, Kengo Kato a, Yasutoshi Koshiba a, Shigeru Saijo a, Kazuto Matsuura a a b c
Department of Head and Neck Surgery, Miyagi Cancer Center, Natori, Miyagi, Japan Department of Pathology, Miyagi Cancer Center, Natori, Miyagi, Japan Department of Diagnostic Radiology, Miyagi Cancer Center, Natori, Miyagi, Japan
A R T I C L E I N F O
A B S T R A C T
Article history: Received 29 April 2015 Accepted 10 June 2015 Available online xxx
We report an extremely rare case of primary clear cell carcinoma (CCC), not otherwise specified (NOS) of the nasal cavity. An 80-year-old woman was referred to our hospital with left nasal obstruction caused by a nasal cavity tumor. The tumor was resected completely with lateral rhinotomy approach. Histopathological examination revealed CCC. CCC metastasis from renal cell carcinoma (RCC), which is at the top of differential diagnosis, was ruled out by the absence of renal tumor at computed tomography (CT). Also, immunohistochemical results of the specimen with vimentin negative and CK7 focally positive excluded the possibility of RCC metastasis. The patient is free from recurrence 1 year after the surgery, and there is no evidence of RCC. In this report histopathological characteristics, especially immunohistochemical properties of primary CCC, NOS of the nasal cavity are presented together with some clinical features of this rare tumor. Also, we refer to histopathogenesis of primary CCC of nasal cavity in relation to myoepithelial carcinoma. Histopathological discussion is further extended to include other CCC and CCC-resembling histologies to confirm the uniqueness of the present case. ß 2015 Published by Elsevier Ireland Ltd.
Keywords: Clear cell carcinoma NOS Nasal cavity Renal cell carcinoma Myoepithelial carcinoma Sinonasal renal cell-like adenocarcinoma Hyalinizing clear cell carcinoma
1. Introduction Sinonasal cancers, which account for 3% of all head and neck cancers, have their origin in the nasal cavity in 20–30% of cases [1]. Secondary or metastatic tumors to the sinonasal tract are rarely seen constituting only 1.5% of all sinonasal cancers [2]. Renal cell carcinoma (RCC), of which the typical histopathology is ‘‘clear cell carcinoma (CCC)’’, is the most frequent primary tumor metastasizing to the sinonasal tract [3]. While most of the primary sinonasal cancers are of squamous cell carcinoma [4], there are a wide variety of histologies including CCC, not otherwise specified (NOS) which is quite rare with only 12 cases reported in English literature [5–9]. Therefore, in spite of its rarity, when the histopathology of a sinonasal tumor proves to be CCC, it is mandatory to determine the nature of the tumor, i.e. whether it is primary, metastatic or even clear-cell like carcinomas, in order to proceed to the further treatment and make the correct prognosis.
* Corresponding author at: Department of Head and Neck Surgery, Miyagi Cancer Center, 47-1 Nodayama, Medeshima-Shiode, Natori, Miyagi 981-1293, Japan. Tel.: +81 22 384 3151; fax: +81 22 384 1174. E-mail address: [email protected] (T. Imai).
Recently we experienced a case of primary CCC, NOS of the nasal cavity, the diagnosis of which was established by in-depth examinations of immunohistochemistry and electron microscopy. In this report, the results of those examinations together with interesting radiological findings are presented. We further deepened the discussion on histopathological characteristics of clear-cell type cancers in the head and neck region. 2. Case report An 80-year-old woman was referred to our hospital for further diagnosis and treatment of her right nasal cavity tumor. She had been suffering from right nasal obstruction for 4 months and purulent nasal discharge for 2 months. At inspection a tumor with a reddish white tint was seen filling the right nasal cavity (Fig. 1a). Computed tomography (CT) (Fig. 1b) and magnetic resonance imaging (MRI) (Fig. 1c and d) demonstrated a tumor, measuring 57 mm in diameter, occupying the nasal cavity and extending posteriorly to the choana. On contrast study, the mass only minimally enhanced without conspicuous vessels, which made a good contrast to RCC metastasis [10]. Inflammatory changes were observed in the right maxillary sinus due to obstruction of the osteomeatal complex. No infiltration into the ethmoid sinus or
http://dx.doi.org/10.1016/j.anl.2015.06.002 0385-8146/ß 2015 Published by Elsevier Ireland Ltd.
Please cite this article in press as: Imai T, et al. Clear cell carcinoma of the nasal cavity: A case report from histopathological viewpoint. Auris Nasus Larynx (2015), http://dx.doi.org/10.1016/j.anl.2015.06.002
G Model
ANL-1991; No. of Pages 4 2
T. Imai et al. / Auris Nasus Larynx xxx (2015) xxx–xxx
Fig. 1. (a) The tumor with a reddish white tint filling the right nasal cavity. (b) CT image of the coronal section. The lateral wall of the nasal cavity is bowed laterally by the tumor. Enhanced MRI images of axial section (c) and coronal section (d). The tumor with only minimal contract enhancement, measuring 57 mm in diameter, occupies the nasal cavity and extends posteriorly to the choana. (e) FDG-PET examination. FDG uptake was significantly high in this tumor (SUV max 17.02). (For interpretation of the references to color in this figure legend, the reader is referred to the web version of the article.)
destruction of the orbital walls was observed. The lateral wall of the nasal cavity was bowed laterally by the tumor, but no direct invasion of the wall was seen. Her past history consisted of myocardial infarction and gastric cancer which was subtotally resected 24 years previously. A biopsy of the tumor had been performed by the referring doctor which gave the diagnosis of ‘‘nasal cavity cancer with histopathological similarity to RCC’’. FDG-PET revealed a significant uptake by this tumor (Fig. 1e). Regional metastasis, distant metastasis, and other primary tumorous lesions were not demonstrated at CT, MRI, or FDGPET. In order to rule out a metastatic lesion from RCC, an abdominal CT with dynamic contrast study was conducted. However we could not find any possible lesions in the bilateral kidneys. Furthermore, upper gastrointestinal endoscopy denied gastric cancer. With a diagnosis of nasal cavity cancer of T1N0, surgical resection was performed with lateral rhinotomy approach. Negative surgical margins and no infiltration to the ethmoid sinus were confirmed at the postoperative pathological examination, and the patient is free from recurrence 1 year after the surgery. The result of histopathological examination was CCC with the similarity to RCC on the H&E stain sections. Relatively small clear cells were seen proliferating as sheets of cells and not forming glandular structures (Fig. 2). Further investigation exploiting immunohistochemical examination was undertaken to definitely differentiate the present case from RCC metastasis. In RCC, CK7 and CK10 are generally negative, vimentin, and CD10 are usually positive [5,11,12]. These and additional markers in our case were as follows (Table 1): CK7 focally positive, CK10, vimentin, and CD10 negative, epithelial membrane antigen (EMA) positive, HMB45 negative, S-100 protein negative, PAS negative. All of these results pathologically favored primary CCC over CCC metastasis from RCC, and there has been no evidence of RCC during the observation period. The results of other immunohistochemical examinations of this tumor (Table 1) were slightly positive for smooth muscle actin (SMA) and diffusely positive for p63 and CK5/6. Since myoepithelial carcinoma (MC) is known to have these immunohistochemical properties as well, and under microscopy, appears as CCC, we proceeded to look into the histopathogenesis of our present case under electron microscopy using paraffin-embedded section. In our case, desmosomes of the tumor developed well (Fig. 3), which is often not the case with MC. This fact, bolstered by the aforementioned immunohistochemical results (EMA positive, S-100 protein negative, vimentin negative), led us to conclude that the present tumor originated from intercalated duct cells rather than myoepithelial cells.
Fig. 2. Histopathological findings of the tumor on the H&E stain sections (a and b). Relatively small clear cells are seen proliferating as sheets of cells and not forming glandular structures. Scale bar: 100 mm.
Please cite this article in press as: Imai T, et al. Clear cell carcinoma of the nasal cavity: A case report from histopathological viewpoint. Auris Nasus Larynx (2015), http://dx.doi.org/10.1016/j.anl.2015.06.002
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ANL-1991; No. of Pages 4 T. Imai et al. / Auris Nasus Larynx xxx (2015) xxx–xxx
3
Table 1 Immunohistochemical findings of the present case, RCC, SRCLA, and MC [5,11,12,14].
a
RCC SRCLA (n = 4) MC Present case
b
CK7
CK20
CD10
Variable +
d
e
+ (1) (focal),
c
a b c d e
+
(3)
+ + (1), + +
Vimentin
S-100
AE1/3
+
Variable + (1), (3) +
Variable + +
(1) +
CK5/6
p63
SMA
Variable + +
+ + (focal)
EMA Variable
+ + (weak)
+
Renal cell carcinoma. Sinonasal renal cell-like adenocarcinoma. Myoepithelial carcinoma. : negative. +: positive.
3. Discussion In sinonasal tract, salivary gland-type cancers are second in frequency to squamous cell carcinoma accounting for 4–8% of all sinonasal malignancies [13], and they are considered to originate from submucosal exocrine glands such as nasal glands. Primary CCC, NOS is a subtype of salivary gland-type cancers which is extremely rare with only 12 cases reported in English literature [5–9]. On the other hand, although uncommon, there are secondary or metastatic CCCs of the sinonasal tract, the most frequent of which is from RCC [3]. Since both primary and RCCderived metastatic CCCs appear quite similar in histopathology, it is practically impossible to differentiate the two under ordinary light microscopy. In fact, the first pathological report of our case was ‘‘RCC-like CCC’’. In the present case, a metastatic CCC from RCC was ruled out both clinically and pathologically. In addition to the fact that no appreciable tumors of the kidney were detected on contrastenhanced CT, the tumor itself in the nasal cavity showed only minimal enhancement on MRI, which contradicts a metastatic tumor from RCC [10]. To our knowledge there has been no such report in the literature as to the enhancing pattern on MRI of primary CCC of the nasal cavity. Pathological examination employing exquisite immunohistochemical staining which consisted of CK7, CK10, vimentin and CD10 was tellingly effective in discriminating the two CCCs. From our present experience, when a diagnosis of CCC for a nasal cavity tumor is obtained, it would not be very difficult to differentiate between primary CCC and RCC metastasis by radiological and immunohistochemical examinations. There is another problem concerning CCC of the sinonasal tract. Histopathologically, some salivary gland-type cancers such as clear cell MC and epithelial–myoepithelial carcinoma have an
appearance of clear cell tumors which may mimic primary CCC, NOS. Clear cell variants of other salivary gland-type cancers, such as squamous cell carcinoma, mucoepidermoid carcinoma, and acinic cell carcinoma, have also the same tendency. Among these confusing histologies MC is especially difficult to differentiate from primary CCC [5,14]. MC has the different cell origin from primary CCC, NOS. The former is considered to derive from myoepithelial cells, while the latter from intercalated duct cells. In the present case, the results of positive EMA as an epithelial marker, negative S-100 protein and vimentin as a myoepithelial marker, slightly positive SMA and diffusely positive p63 and CK5/6 suggested the possibility of myoepithelial cell and prompted us to further investigate with electron microscopy. We found well-developing desmosomes, characteristic of intercalated duct cells, in the tumor cells and discarded the possibility of myoepithelial cell origin. Recently, a disease concept of hyalinizing clear cell carcinoma (HCCC) was established by Weinreb et al. [15]. HCCC is a rare minor salivary gland clear cell tumor with hyalinizing stroma which is now included in ‘‘CCC, NOS’’ by the World Health Organization (WHO). The majority of HCCCs are reported to be diffusely positive for p63 and CK5/6 owing to squamous differentiation [15]. In that sense our case could be a potential HCCC. In HCCC, EWSR1–ATF1 fusion is reported to be consistently identified [15], but in the present case no such fusion was detected in the tumor (data not shown). Moreover, hyalinizing stroma which is considered to be specific to HCCC was not demonstrated in the present case. Consequently, we interpreted the histology of the present case to be CCC, NOS rather than HCCC. Primary CCC in the nasal cavity is very rare, and to date, only 12 cases have been reported in English literature [5–9]. Among these cases, four cases of CCC were reported as a new entity of sinonasal renal cell-like adenocarcinoma (SRCLA), a histologic mimic of RCC. In SRCLA, CK7 is positive, and vimentin is negative in all cases [5], and these immunohistochemical results distinguish SRCLA from RCC. The concept of SRCLA was elaborated by Storck et al., and it is claimed to be strictly distinguished from CCC, NOS [5]. Our case had a microscopic appearance closely resembling that of SRCLA and the similar immunohistochemical staining pattern as well. Actually, immunohistochemical staining patterns of SRCLA and CCC are reported to be quite similar [5]. However, in the present case, small clear cells were seen proliferating as sheets of cells and did not form glandular structures whereas in SRCLA glandular growth pattern is usually observed. From this morphological reason we would refrain from putting forward the pathological diagnosis of SRCLA for the present case and would rather remain with the diagnosis of CCC, NOS of salivary gland-type cancer originating from the intercalated duct cells of submucosal exocrine glands. Conflict of interest statement
Fig. 3. Electron microscopic findings of the tumor using paraffin-embedded section. Desmosomes (broken arrows) have developed well.
The authors declare that they have no conflict of interest.
Please cite this article in press as: Imai T, et al. Clear cell carcinoma of the nasal cavity: A case report from histopathological viewpoint. Auris Nasus Larynx (2015), http://dx.doi.org/10.1016/j.anl.2015.06.002
G Model
ANL-1991; No. of Pages 4 T. Imai et al. / Auris Nasus Larynx xxx (2015) xxx–xxx
4
References [1] Robin PE, Powell DJ, Stansbie JM. Carcinoma of the nasal cavity and paranasal sinuses: incidence and presentation of different histological types. Clin Otolaryngol Allied Sci 1979;4:431–56. [2] Weber AL, Stanton AC. Malignant tumors of the paranasal sinuses: radiologic, clinical, and histopathologic evaluation of 200 cases. Head Neck Surg 1984;6:761–76. [3] Bernstein JM, Montgomery WW, Balogh Jr K. Metastatic tumors to the maxilla, nose, and paranasal sinuses. Laryngoscope 1966;76:621–50. [4] Turner JH, Reh DD. Incidence and survival in patients with sinonasal cancer: a historical analysis of population-based data. Head Neck 2012;34:877–85. [5] Storck K, Hadi UM, Simpson R, Ramer M, Brandwein-Gensler M. Sinonasal renal cell-like adenocarcinoma: a report on four patients. Head Neck Pathol 2008;2:75–80. [6] Zur KB, Brandwein M, Wang B, Som P, Gordon R, Urken ML. Primary description of a new entity, renal cell-like carcinoma of the nasal cavity: van Meegeren in the house of Vermeer. Arch Otolaryngol Head Neck Surg 2002;128:441–7. [7] Moh’d Hadi U, Kahwaji GJ, Mufarrij AA, Tawii A, Noureddine B. Low grade primary clear cell carcinoma of the sinonasal tract. Rhinology 2002;40:44–7.
[8] Sahasrabudhe NS, Puranik SC, Holla VV. Clear cell adenocarcinoma of the maxillary sinus: a case report. Indian J Pathol Microbiol 2003;46:93–5. [9] Zhao W, Yang L, Wang L, Zuo W, Yuan S, Yu J, et al. Primary clear cell carcinoma of nasal cavity: report of six cases and review of literature. Int J Clin Exp Med 2014;7:5469–76. [10] Terada T. Renal cell carcinoma metastatic to the nasal cavity. Int J Clin Exp Pathol 2012;5:588–91. [11] Allory Y, Bazille C, Vieillefond A, Molinie´ V, Cochand-Priollet B, Cussenot O, et al. Profiling and classification tree applied to renal epithelial tumours. Histopathology 2008;52:158–66. [12] Zhou M, Roma A, Magi-Galluzzi C. The usefulness of immunohistochemical markers in the differential diagnosis of renal neoplasms. Clin Lab Med 2005;25:247–57. [13] Pantvaidya GH, Vaidya AD, Metgudmath R, Kane SV, D’Cruz AK. Minor salivary gland tumors of the sinonasal region: results of a retrospective analysis with review of literature. Head Neck 2012;34:1704–10. [14] Yang S, Li L, Zeng M, Zhu X, Zhang J, Chen X. Myoepithelial carcinoma of intraoral minor salivary glands: a clinicopathological study of 7 cases and review of the literature. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2010;110:85–93. [15] Weinreb I. Hyalinizing clear cell carcinoma of salivary gland: a review and update. Head Neck Pathol 2013;7:S20–9.
Please cite this article in press as: Imai T, et al. Clear cell carcinoma of the nasal cavity: A case report from histopathological viewpoint. Auris Nasus Larynx (2015), http://dx.doi.org/10.1016/j.anl.2015.06.002
ANL-1991; No. of Pages 4 Auris Nasus Larynx xxx (2015) xxx–xxx
Contents lists available at ScienceDirect
Auris Nasus Larynx journal homepage: www.elsevier.com/locate/anl
Clear cell carcinoma of the nasal cavity: A case report from histopathological viewpoint Takayuki Imai a,*, Ikuro Satoh b, Ko Matsumoto c, Shigemi Ito b, Yukinori Asada a, Kengo Kato a, Yasutoshi Koshiba a, Shigeru Saijo a, Kazuto Matsuura a a b c
Department of Head and Neck Surgery, Miyagi Cancer Center, Natori, Miyagi, Japan Department of Pathology, Miyagi Cancer Center, Natori, Miyagi, Japan Department of Diagnostic Radiology, Miyagi Cancer Center, Natori, Miyagi, Japan
A R T I C L E I N F O
A B S T R A C T
Article history: Received 29 April 2015 Accepted 10 June 2015 Available online xxx
We report an extremely rare case of primary clear cell carcinoma (CCC), not otherwise specified (NOS) of the nasal cavity. An 80-year-old woman was referred to our hospital with left nasal obstruction caused by a nasal cavity tumor. The tumor was resected completely with lateral rhinotomy approach. Histopathological examination revealed CCC. CCC metastasis from renal cell carcinoma (RCC), which is at the top of differential diagnosis, was ruled out by the absence of renal tumor at computed tomography (CT). Also, immunohistochemical results of the specimen with vimentin negative and CK7 focally positive excluded the possibility of RCC metastasis. The patient is free from recurrence 1 year after the surgery, and there is no evidence of RCC. In this report histopathological characteristics, especially immunohistochemical properties of primary CCC, NOS of the nasal cavity are presented together with some clinical features of this rare tumor. Also, we refer to histopathogenesis of primary CCC of nasal cavity in relation to myoepithelial carcinoma. Histopathological discussion is further extended to include other CCC and CCC-resembling histologies to confirm the uniqueness of the present case. ß 2015 Published by Elsevier Ireland Ltd.
Keywords: Clear cell carcinoma NOS Nasal cavity Renal cell carcinoma Myoepithelial carcinoma Sinonasal renal cell-like adenocarcinoma Hyalinizing clear cell carcinoma
1. Introduction Sinonasal cancers, which account for 3% of all head and neck cancers, have their origin in the nasal cavity in 20–30% of cases [1]. Secondary or metastatic tumors to the sinonasal tract are rarely seen constituting only 1.5% of all sinonasal cancers [2]. Renal cell carcinoma (RCC), of which the typical histopathology is ‘‘clear cell carcinoma (CCC)’’, is the most frequent primary tumor metastasizing to the sinonasal tract [3]. While most of the primary sinonasal cancers are of squamous cell carcinoma [4], there are a wide variety of histologies including CCC, not otherwise specified (NOS) which is quite rare with only 12 cases reported in English literature [5–9]. Therefore, in spite of its rarity, when the histopathology of a sinonasal tumor proves to be CCC, it is mandatory to determine the nature of the tumor, i.e. whether it is primary, metastatic or even clear-cell like carcinomas, in order to proceed to the further treatment and make the correct prognosis.
* Corresponding author at: Department of Head and Neck Surgery, Miyagi Cancer Center, 47-1 Nodayama, Medeshima-Shiode, Natori, Miyagi 981-1293, Japan. Tel.: +81 22 384 3151; fax: +81 22 384 1174. E-mail address: [email protected] (T. Imai).
Recently we experienced a case of primary CCC, NOS of the nasal cavity, the diagnosis of which was established by in-depth examinations of immunohistochemistry and electron microscopy. In this report, the results of those examinations together with interesting radiological findings are presented. We further deepened the discussion on histopathological characteristics of clear-cell type cancers in the head and neck region. 2. Case report An 80-year-old woman was referred to our hospital for further diagnosis and treatment of her right nasal cavity tumor. She had been suffering from right nasal obstruction for 4 months and purulent nasal discharge for 2 months. At inspection a tumor with a reddish white tint was seen filling the right nasal cavity (Fig. 1a). Computed tomography (CT) (Fig. 1b) and magnetic resonance imaging (MRI) (Fig. 1c and d) demonstrated a tumor, measuring 57 mm in diameter, occupying the nasal cavity and extending posteriorly to the choana. On contrast study, the mass only minimally enhanced without conspicuous vessels, which made a good contrast to RCC metastasis [10]. Inflammatory changes were observed in the right maxillary sinus due to obstruction of the osteomeatal complex. No infiltration into the ethmoid sinus or
http://dx.doi.org/10.1016/j.anl.2015.06.002 0385-8146/ß 2015 Published by Elsevier Ireland Ltd.
Please cite this article in press as: Imai T, et al. Clear cell carcinoma of the nasal cavity: A case report from histopathological viewpoint. Auris Nasus Larynx (2015), http://dx.doi.org/10.1016/j.anl.2015.06.002
G Model
ANL-1991; No. of Pages 4 2
T. Imai et al. / Auris Nasus Larynx xxx (2015) xxx–xxx
Fig. 1. (a) The tumor with a reddish white tint filling the right nasal cavity. (b) CT image of the coronal section. The lateral wall of the nasal cavity is bowed laterally by the tumor. Enhanced MRI images of axial section (c) and coronal section (d). The tumor with only minimal contract enhancement, measuring 57 mm in diameter, occupies the nasal cavity and extends posteriorly to the choana. (e) FDG-PET examination. FDG uptake was significantly high in this tumor (SUV max 17.02). (For interpretation of the references to color in this figure legend, the reader is referred to the web version of the article.)
destruction of the orbital walls was observed. The lateral wall of the nasal cavity was bowed laterally by the tumor, but no direct invasion of the wall was seen. Her past history consisted of myocardial infarction and gastric cancer which was subtotally resected 24 years previously. A biopsy of the tumor had been performed by the referring doctor which gave the diagnosis of ‘‘nasal cavity cancer with histopathological similarity to RCC’’. FDG-PET revealed a significant uptake by this tumor (Fig. 1e). Regional metastasis, distant metastasis, and other primary tumorous lesions were not demonstrated at CT, MRI, or FDGPET. In order to rule out a metastatic lesion from RCC, an abdominal CT with dynamic contrast study was conducted. However we could not find any possible lesions in the bilateral kidneys. Furthermore, upper gastrointestinal endoscopy denied gastric cancer. With a diagnosis of nasal cavity cancer of T1N0, surgical resection was performed with lateral rhinotomy approach. Negative surgical margins and no infiltration to the ethmoid sinus were confirmed at the postoperative pathological examination, and the patient is free from recurrence 1 year after the surgery. The result of histopathological examination was CCC with the similarity to RCC on the H&E stain sections. Relatively small clear cells were seen proliferating as sheets of cells and not forming glandular structures (Fig. 2). Further investigation exploiting immunohistochemical examination was undertaken to definitely differentiate the present case from RCC metastasis. In RCC, CK7 and CK10 are generally negative, vimentin, and CD10 are usually positive [5,11,12]. These and additional markers in our case were as follows (Table 1): CK7 focally positive, CK10, vimentin, and CD10 negative, epithelial membrane antigen (EMA) positive, HMB45 negative, S-100 protein negative, PAS negative. All of these results pathologically favored primary CCC over CCC metastasis from RCC, and there has been no evidence of RCC during the observation period. The results of other immunohistochemical examinations of this tumor (Table 1) were slightly positive for smooth muscle actin (SMA) and diffusely positive for p63 and CK5/6. Since myoepithelial carcinoma (MC) is known to have these immunohistochemical properties as well, and under microscopy, appears as CCC, we proceeded to look into the histopathogenesis of our present case under electron microscopy using paraffin-embedded section. In our case, desmosomes of the tumor developed well (Fig. 3), which is often not the case with MC. This fact, bolstered by the aforementioned immunohistochemical results (EMA positive, S-100 protein negative, vimentin negative), led us to conclude that the present tumor originated from intercalated duct cells rather than myoepithelial cells.
Fig. 2. Histopathological findings of the tumor on the H&E stain sections (a and b). Relatively small clear cells are seen proliferating as sheets of cells and not forming glandular structures. Scale bar: 100 mm.
Please cite this article in press as: Imai T, et al. Clear cell carcinoma of the nasal cavity: A case report from histopathological viewpoint. Auris Nasus Larynx (2015), http://dx.doi.org/10.1016/j.anl.2015.06.002
G Model
ANL-1991; No. of Pages 4 T. Imai et al. / Auris Nasus Larynx xxx (2015) xxx–xxx
3
Table 1 Immunohistochemical findings of the present case, RCC, SRCLA, and MC [5,11,12,14].
a
RCC SRCLA (n = 4) MC Present case
b
CK7
CK20
CD10
Variable +
d
e
+ (1) (focal),
c
a b c d e
+
(3)
+ + (1), + +
Vimentin
S-100
AE1/3
+
Variable + (1), (3) +
Variable + +
(1) +
CK5/6
p63
SMA
Variable + +
+ + (focal)
EMA Variable
+ + (weak)
+
Renal cell carcinoma. Sinonasal renal cell-like adenocarcinoma. Myoepithelial carcinoma. : negative. +: positive.
3. Discussion In sinonasal tract, salivary gland-type cancers are second in frequency to squamous cell carcinoma accounting for 4–8% of all sinonasal malignancies [13], and they are considered to originate from submucosal exocrine glands such as nasal glands. Primary CCC, NOS is a subtype of salivary gland-type cancers which is extremely rare with only 12 cases reported in English literature [5–9]. On the other hand, although uncommon, there are secondary or metastatic CCCs of the sinonasal tract, the most frequent of which is from RCC [3]. Since both primary and RCCderived metastatic CCCs appear quite similar in histopathology, it is practically impossible to differentiate the two under ordinary light microscopy. In fact, the first pathological report of our case was ‘‘RCC-like CCC’’. In the present case, a metastatic CCC from RCC was ruled out both clinically and pathologically. In addition to the fact that no appreciable tumors of the kidney were detected on contrastenhanced CT, the tumor itself in the nasal cavity showed only minimal enhancement on MRI, which contradicts a metastatic tumor from RCC [10]. To our knowledge there has been no such report in the literature as to the enhancing pattern on MRI of primary CCC of the nasal cavity. Pathological examination employing exquisite immunohistochemical staining which consisted of CK7, CK10, vimentin and CD10 was tellingly effective in discriminating the two CCCs. From our present experience, when a diagnosis of CCC for a nasal cavity tumor is obtained, it would not be very difficult to differentiate between primary CCC and RCC metastasis by radiological and immunohistochemical examinations. There is another problem concerning CCC of the sinonasal tract. Histopathologically, some salivary gland-type cancers such as clear cell MC and epithelial–myoepithelial carcinoma have an
appearance of clear cell tumors which may mimic primary CCC, NOS. Clear cell variants of other salivary gland-type cancers, such as squamous cell carcinoma, mucoepidermoid carcinoma, and acinic cell carcinoma, have also the same tendency. Among these confusing histologies MC is especially difficult to differentiate from primary CCC [5,14]. MC has the different cell origin from primary CCC, NOS. The former is considered to derive from myoepithelial cells, while the latter from intercalated duct cells. In the present case, the results of positive EMA as an epithelial marker, negative S-100 protein and vimentin as a myoepithelial marker, slightly positive SMA and diffusely positive p63 and CK5/6 suggested the possibility of myoepithelial cell and prompted us to further investigate with electron microscopy. We found well-developing desmosomes, characteristic of intercalated duct cells, in the tumor cells and discarded the possibility of myoepithelial cell origin. Recently, a disease concept of hyalinizing clear cell carcinoma (HCCC) was established by Weinreb et al. [15]. HCCC is a rare minor salivary gland clear cell tumor with hyalinizing stroma which is now included in ‘‘CCC, NOS’’ by the World Health Organization (WHO). The majority of HCCCs are reported to be diffusely positive for p63 and CK5/6 owing to squamous differentiation [15]. In that sense our case could be a potential HCCC. In HCCC, EWSR1–ATF1 fusion is reported to be consistently identified [15], but in the present case no such fusion was detected in the tumor (data not shown). Moreover, hyalinizing stroma which is considered to be specific to HCCC was not demonstrated in the present case. Consequently, we interpreted the histology of the present case to be CCC, NOS rather than HCCC. Primary CCC in the nasal cavity is very rare, and to date, only 12 cases have been reported in English literature [5–9]. Among these cases, four cases of CCC were reported as a new entity of sinonasal renal cell-like adenocarcinoma (SRCLA), a histologic mimic of RCC. In SRCLA, CK7 is positive, and vimentin is negative in all cases [5], and these immunohistochemical results distinguish SRCLA from RCC. The concept of SRCLA was elaborated by Storck et al., and it is claimed to be strictly distinguished from CCC, NOS [5]. Our case had a microscopic appearance closely resembling that of SRCLA and the similar immunohistochemical staining pattern as well. Actually, immunohistochemical staining patterns of SRCLA and CCC are reported to be quite similar [5]. However, in the present case, small clear cells were seen proliferating as sheets of cells and did not form glandular structures whereas in SRCLA glandular growth pattern is usually observed. From this morphological reason we would refrain from putting forward the pathological diagnosis of SRCLA for the present case and would rather remain with the diagnosis of CCC, NOS of salivary gland-type cancer originating from the intercalated duct cells of submucosal exocrine glands. Conflict of interest statement
Fig. 3. Electron microscopic findings of the tumor using paraffin-embedded section. Desmosomes (broken arrows) have developed well.
The authors declare that they have no conflict of interest.
Please cite this article in press as: Imai T, et al. Clear cell carcinoma of the nasal cavity: A case report from histopathological viewpoint. Auris Nasus Larynx (2015), http://dx.doi.org/10.1016/j.anl.2015.06.002
G Model
ANL-1991; No. of Pages 4 T. Imai et al. / Auris Nasus Larynx xxx (2015) xxx–xxx
4
References [1] Robin PE, Powell DJ, Stansbie JM. Carcinoma of the nasal cavity and paranasal sinuses: incidence and presentation of different histological types. Clin Otolaryngol Allied Sci 1979;4:431–56. [2] Weber AL, Stanton AC. Malignant tumors of the paranasal sinuses: radiologic, clinical, and histopathologic evaluation of 200 cases. Head Neck Surg 1984;6:761–76. [3] Bernstein JM, Montgomery WW, Balogh Jr K. Metastatic tumors to the maxilla, nose, and paranasal sinuses. Laryngoscope 1966;76:621–50. [4] Turner JH, Reh DD. Incidence and survival in patients with sinonasal cancer: a historical analysis of population-based data. Head Neck 2012;34:877–85. [5] Storck K, Hadi UM, Simpson R, Ramer M, Brandwein-Gensler M. Sinonasal renal cell-like adenocarcinoma: a report on four patients. Head Neck Pathol 2008;2:75–80. [6] Zur KB, Brandwein M, Wang B, Som P, Gordon R, Urken ML. Primary description of a new entity, renal cell-like carcinoma of the nasal cavity: van Meegeren in the house of Vermeer. Arch Otolaryngol Head Neck Surg 2002;128:441–7. [7] Moh’d Hadi U, Kahwaji GJ, Mufarrij AA, Tawii A, Noureddine B. Low grade primary clear cell carcinoma of the sinonasal tract. Rhinology 2002;40:44–7.
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Please cite this article in press as: Imai T, et al. Clear cell carcinoma of the nasal cavity: A case report from histopathological viewpoint. Auris Nasus Larynx (2015), http://dx.doi.org/10.1016/j.anl.2015.06.002
