Background
This carcinoma must be distinguished from nasopharyngeal carcinomas. Indeed many studies often lump these tumors with the latter diagnosis. It is a distinct clinical-pathologic entity and is not related to Epstein-Barr Virus infection like the latter tumor. The nasal cavity is the most common location followed by the ethmoid and maxillary sinuses.
OUTLINE
EPIDEMIOLOGY CHARACTERIZATION SEX (M:F)3:1
PATHOGENESIS CHARACTERIZATION Lack of EBV association Am J Surg Pathol 2001;25:156-163
If stringent histologic criteria are applied to the diagnosis of SNUC, then the tumor is not associated with EBV
SPECIAL STAINS/
IMMUNOPEROXIDASE/
OTHERCHARACTERIZATION Special stains Immunoperoxidase Am J Surg Pathol 2001;25:156-163
All 25 tumors were negative for EBER-1 by ISH
Ki-67
Negative in one case
1+ in nine
2+ in six
3+ in five
4+ in oneP53
Negative in nine
1+ in five
2+ in two
3+ in none
4+ in sixCD99
Strongly positive in 3 of 22 (14%)Variably intense focal staining for EMA was present in 4 of 22 (18%)
NSE faintly stained 4 of 22 (18%)Chromogranin, synaptophysin, PLAP, CEA, and LMP-1 were negative (0 of 22)
CYTOKERATINS
Sinonasal undifferentiated carcinoma, nasopharyngeal-type undifferentiated carcinoma, and keratinizing and nonkeratinizing squamous cell carcinoma express different cytokeratin patterns.Franchi A, Moroni M, Massi D, Paglierani M, Santucci M.
Am J Surg Pathol 2002 Dec;26(12):1597-604 Abstract quote Sinonasal undifferentiated carcinoma (SNUC) is a highly aggressive malignant neoplasm that is often difficult to distinguish from other poorly differentiated carcinomas arising in the sinonasal tract.
To search for a differential cytokeratin (CK) expression that could be useful for diagnostic purposes, we compared the expression of a large panel of CKs in a series of 6 SNUCs, 10 poorly differentiated squamous cell carcinomas (SCCs), 10 nonkeratinizing squamous cell carcinomas (NKSCCs), and 5 nasopharyngeal-type undifferentiated carcinomas (NPTCs). SCC, NKSCC, and NPTC frequently showed immunoreactivity for CK5/CK6, CK8, CK13, and CK19. In addition, SCC and NKSCC expressed CK14, which was not detected in NPTC, and SCC expressed CK7 (60% of cases) and CK4 (30% of cases), which were absent in NKSCC and NPTC. Three NKSCCs were associated with a Schneiderian papilloma, and the results of the immunostaining were similar in the two components, with the exception of CK4 and CK7, which were expressed by the papilloma and not by the carcinoma.
In contrast to other carcinomas, SNUC was characterized by the exclusive expression of CKs of simple epithelia, such as CK8 (100% of cases), CK7 (50% of cases), and CK19 (50% of cases). Thus, there are significant differences in the pattern of CK expression between SNUC, SCC, NKSCC, and NPTC, which could be of diagnostic aid. Moreover, these findings support the hypothesis that SNUC is a separate entity from SCC and NPTC of the sinonasal tract.
DIFFERENTIAL DIAGNOSIS KEY DIFFERENTIATING FEATURES Nasopharyngeal carcinoma Sinonasal Undifferentiated Carcinoma and Nasopharyngeal-Type Undifferentiated Carcinoma
Two Clinically, Biologically, and Histopathologically Distinct EntitiesYung-Ming Jeng, M.D.; Ming-Tse Sung, M.D.; Chia-Lang Fang, M.D., M.S.; Hsuan-Ying Huang, M.D.; Tsui-Lien Mao, M.D., M.S.; Wei Cheng, M.D., M.S.; Cheng-Hsiang Hsiao, M.D.
From the Department of Pathology (Y.-M.J., T.-L.M., W.C., C.-H.H.), National Taiwan University Hospital, Taipei, the Department of Pathology (M.-T.S., H.-Y.H.), Chang-Gung Memorial Hospital, Koahsiung, and the Department of Pathology (C.-L.F.), Taipei Medical University-affiliated Taipei Wan Fang Hospital, Taipei, Taiwan.
Am J Surg Pathol 2002;26:371-376 Abstract quote Sinonasal undifferentiated carcinoma (SNUC) is a rare aggressive neoplasm arising in the nasal cavity and paranasal sinuses. Primary sinonasal nasopharyngeal-type undifferentiated carcinoma (PSNPC) is an even rarer tumor that has not been adequately reported. Both tumors have been reported to be associated with EpsteinBarr virus (EBV).
We studied the clinicopathologic features and EBV status of 36 SNUC and 13 PSNPC patients from Taiwan, an EBV endemic area.
The median age of SNUC patients was 53 years (range 2076 years), with a male/female ratio of approximately 2:1. Five patients had histories of previous nasopharyngeal carcinoma treated with irradiation 626 years earlier. The most common locations were nasal cavity and ethmoid sinus. Orbital and intracranial invasion and distant metastasis were frequent findings. The median survival was 10 months. All 36 tumors were negative for EBER-1 by in situ hybridization.
The median age of PSNPC patients was 58 years (range 3675 years), with a male/female ratio of approximately 2:1. The most common location is nasal cavity. Eight patients achieved disease-free survival. Eight tumors had the morphology of lymphoepithelioma, whereas significant inflammatory infiltrate was not detected in the other five tumors. All 13 tumors were positive for EBER-1 by in situ hybridization.
Because of the difference in the relation with EBV, prognosis, and response to radiotherapy, SNUC and PSNPC should be considered as two entirely different entities. The most important criteria for PSNPC are vesicular nuclei, syncytial pattern, spindle cells, and absence of necrosis.
Olfactory neuroblastoma Homer-Wright rosettes or neurofibrillary stroma
No nuclear pleomorphism, prominent mitoses, or vascular invasion
Keratin and EMA negative
Synaptophysin and S-100 positive
PROGNOSIS AND TREATMENT CHARACTERIZATION Prognostic Factors Failure to eradicate local disease with extension into the critical adjacent tissues (e.g., brain, orbit) was the cause of death in most patients Survival Otolaryngol Head Neck Surg 1993;108:697–700.
Am J Surg Pathol 2001;25:156-163
Am J Otolaryngol 1996:17;167–71.Median 18 months
Follow-up data for the original series of cases suggested that the prognosis for patients with localized disease might be better
One study documents three cases with extended survival with two of these patients received autologous bone marrow transplantation, and one of the transplant recipients subsequently underwent a second radical procedure to remove recurrent disease
Both patients survived 9 years after diagnosis but ultimately died of disease, emphasizing that 5-year disease-free survivals cannot be equated with cureOne patient remains free of disease 10 years after tumor resection
Sinonasal undifferentiated carcinoma: a 10-year experience.
Righi PD, Francis F, Aron BS, Weitzner S, Wilson KM, Gluckman J.
Department of Otolaryngology-Head and Neck Surgery, Indiana University Medical Center, Indianapolis 46202, USA.
Am J Otolaryngol 1996 May-Jun;17(3):167-71 Abstract quote
PURPOSE: Sinonasal undifferentiated carcinoma (SNUC) is a rare and aggressive malignancy of the paranasal sinuses and nasal cavity. Of the few reported series, most indicate a dismal prognosis. In this report, the clinical presentation, histopathologic criteria used for diagnosis, mode of treatment, and outcome are evaluated in seven patients with SNUC.
MATERIALS AND METHODS: Seven patients with SNUC treated at the University of Cincinnati between 1983 and 1993 were analyzed retrospectively.
RESULTS: Most of the patients presented with extensive local disease, and two patients also had cervical metastases. All except one were treated using a multimodality approach. Four of the seven patients died of disease (DOD), with a mean survival of only 11.5 months following treatment. Inability to eradicate local disease was responsible for treatment failure in all cases. Three patients have achieved short-term control of disease following combined therapy, but one is at high risk for recurrence.
CONCLUSION: SNUC was associated with an overall poor prognosis in our series despite aggressive treatment. Control of local disease was the central therapeutic consideration. Intensive multimodality therapy is recommended for all patients with SNUC.
METASTASES Disseminated metastases common VASCULAR ENDOTHELIAL GROWTH FACTOR
- Prognostic significance of microvessel density and vascular endothelial growth factor expression in sinonasal carcinomas.
Valente G, Mamo C, Bena A, Prudente E, Cavaliere C, Kerim S, Nicotra G, Comino A, Palestro G, Isidoro C, Beatrice F.
Pathology Section, Department of Medical Sciences, Amedeo Avogadro University Medical School, Novara, Italy.
Hum Pathol. 2006 Apr;37(4):391-400. Epub 2006 Feb 8. Abstract quote
The prognostic significance of microvessel density and proliferative activity of the neoplastic cells, evaluated respectively by CD31 and Ki-67 positivity, and immunohistochemical expression of vascular endothelial growth factor (VEGF) was retrospectively investigated in 105 cases of sinonasal carcinoma (80 surgical specimens and 25 biopsies).
The most represented histologic types were intestinal-type adenocarcinoma found in 36 patients (34.3%), squamous cell carcinoma (SCC) in 34 (32.4%), mucinous adenocarcinoma (mainly made up of signet-ring cell patterns) in 15 (14.3%), and adenoid cystic carcinoma in 7 (6.7%). Microvessel density values (in vessels per square millimeter), VEGF, and Ki-67 were not dependent on histologic type but were rather correlated to the histologic grading in SCC. Clinical data were available for 92 (87.6%) of 105 patients, with minimum follow-up of 48 months. Most of the patients (81.5%) were at an advanced stage (T3-T4) at diagnosis. The values of all markers were correlated to tumor stage (P = .03).
Multivariate analysis showed that both microvessel density and proliferative activity of the neoplastic cells were independent prognostic parameters (mortality hazard ratio, 1.33 and 1.60, respectively). Although VEGF expression was not correlated to prognosis on the whole series (P = .06), it was a powerful prognostic marker when the analysis was restricted to the group of SCCs (hazard ratio, 3.02; 90% confidence interval, 1.58-5.80).
These results show that tumor neoangiogenesis, expressed by microvessel density, together with proliferative activity, is a pathologic marker with a strong prognostic impact in sinonasal carcinomas. Therefore, it may be a useful tool in this field so as to carry out therapeutic protocol planning, which may be further enhanced by the adoption of the more recent antiangiogenic molecules.TREATMENT A combination therapy of continuous superselective intraarterial carboplatin infusion and radiation therapy for locally advanced head and neck carcinoma. Phase I study.
Fuwa N, Ito Y, Matsumoto A, Kamata M, Kodaira T, Furutani K, Sasaoka M, Kimura Y, Morita K.
Department of Radiation Oncology, Aichi Cancer Center Hospital, Chikusaku, Nagoya, Japan.
Cancer 2000 Nov 15;89(10):2099-105 Abstract quote
ACKGROUND: To improve the treatment result for locally advanced head and neck carcinoma, the authors used a combination of radiotherapy with superselective continuous intraarterial therapy using carboplatin. The dose limiting toxicity (DLT), maximum tolerated dose (MTD), and treatment effectiveness were tested in Phase I and II protocols.
PATIENTS AND METHODS. Thirty-five patients were entered into the study from August 1992 to May 1997. The target arteries were the lingual artery in 18 cases, facial artery in 5 cases, maxillary artery in 11 cases, and external carotid artery initially changing to lingual artery in 1 case. Escalating daily carboplatin doses were tested, starting from 10 mg/m(2) (total dose, 360 or 400 mg/m(2)) to 15 mg/m(2) (total dose, 405 or 450 mg/m(2)) and then 20 mg/m(2) (total dose, 460 or 500 mg/m(2)). Radiotherapy was administered using a 6-megavolt linear accelerator to a total dose of 50-60 grays. Interstitial radiotherapy boost also was used for carcinoma of the tongue.
RESULTS: Excluding 3 patients who discontinued treatment, the treatment results of 32 patients were complete response in 21 cases, partial response in 10 cases, and no change in 1 case. Neutropenia was the DLT, and the MTD was 500 mg/m(2). The local control rate was 64%.
CONCLUSIONS: Superselective continuous intraarterial carboplatin and concurrent radiation therapy can be delivered safely with good efficacy for locally advanced carcinomas of the tongue and base of the tongue. Surgical treatment of these diseases usually incurs severe functional loss. This current approach may be a breakthrough in these cancers. Copyright 2000 American Cancer Society.
High-dose intra-arterial cisplatin and concurrent hyperfractionated radiation therapy in patients with locally advanced primary squamous cell carcinoma of the head and neck: report of a phase II study.
Regine WF, Valentino J, John W, Storey G, Sloan D, Kenady D, Patel P, Pulmano C, Arnold SM, Mohiuddin M.
Department of Radiation Medicine, University of Kentucky, 800 Rose Street, Lexington, Kentucky 40536-0293, USA.
Head Neck 2000 Sep;22(6):543-9 Abstract quote
BACKGROUND: This phase II study evaluates the tolerability and efficacy of concurrent hyperfractionated radiation therapy (HFX-RT) and high-dose intra-arterial (IA) cisplatin in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN).
METHODS: Between December 1995 and November 1997, 20 patients with locally advanced T4/T3 SCCHN were treated with HFX-RT (76.8-79.2 Gy at 1.2 Gy bid over 6-7 weeks) and high-dose IA cisplatin (150 mg/m(2) given at the start of RT boost treatment [start of week 6]). Seventeen patients (85%) had T4 disease, and 14 (70%) had N2/ N3 disease.
RESULTS: Grade 3-5 acute toxicity was limited to one grade 4 (5%) and 14 grade 3 (70%) mucosal events. No grade 3/4 hematologic toxicity was observed. Median weight loss during therapy was 9% (range, 2%-16%). Eighteen patients had complete response (90%) at the primary site; 14 were confirmed pathologically. Among 17 patients with positive neck disease, 16 (94%) achieved complete response in the neck, including 12 of 13 patients with N2/N3 disease who underwent planned neck dissection. Active follow-up ranges from 12 to 32 months (median, 20 months) with 11 patients alive without disease, 5 dead of disease, and 4 dead of intercurrent disease. Eighteen patients (90%) remained disease free at the primary site, and the locoregional control rate is 80%.
CONCLUSIONS: High-dose IA cisplatin and concurrent HFX-RT as used in this study is feasible and warrants further investigation. The high complete response rate and low grade 4 toxicity in this highly unfavorable subset of patients appears better than previously reported chemoradiation regimens for more favorable patients.
High-dose intra-arterial cisplatin therapy followed by radiation therapy for advanced squamous cell carcinoma of the head and neck.
Wilson WR, Siegel RS, Harisiadis LA, Davis DO, Nguyen HH, Bank WO.
Division of Hematology and Oncology, George Washington University Medical Center, 2150 Pennsylvania Ave, NW, Suite 3-428, Washington, DC 20037, USA.
Arch Otolaryngol Head Neck Surg 2001 Jul;127(7):809-12 Abstract quote
OBJECTIVE: To assess the effectiveness of a protocol consisting of 4 cycles of high-dose intra-arterial cisplatin infusions followed by radiation therapy for improving chemotherapy response rates, organ preservation, and survival in patients with advanced-stage untreated and previously treated squamous cell carcinoma of the head and neck.
DESIGN AND SETTING: A prospective study of sequentially enrolled patients treated in an academic medical center. The Kaplan-Meier method was used for survival analysis.
PATIENTS: Fifty-eight nonpregnant adults, 18 years of age or older, with measurable untreated or recurrent advanced biopsy-proven squamous cell carcinoma of the head and neck.
MAIN OUTCOME MEASURES: Response rate to targeted intra-arterial cisplatin infusions, organ preservation, and survival.
RESULTS: Fifty-eight patients (44 men and 14 women) were followed up for at least 2 years (median duration of follow-up, 27 months). Twenty-nine (67%) of the 43 previously untreated patients had a complete response to intra-arterial cisplatin therapy. Of the untreated patients, 28 are alive and disease free after a median follow-up time of 30 months. Five of the patients with recurrent disease had a complete response to intra-arterial cisplatin therapy. There were 4 survivors after a median follow-up time of 17.5 months. Of note, there were no deaths or serious complications related to the treatment in either group.
CONCLUSIONS: High-dose intra-arterial cisplatin therapy provides a high complete and partial response rate (91%). The combination of high-dose intra-arterial cisplatin and radiation therapy is effective in improving survival and organ preservation rates in patients with previously untreated, advanced squamous cell carcinoma of the head and neck. This treatment protocol is much less effective for recurrent disease.
Am J Surg Pathol 2001;25:156-163
Henry JB. Clinical Diagnosis and Management by Laboratory Methods. Twentieth Edition. WB Saunders. 2001.
Rosai J. Ackerman's Surgical Pathology. Ninth Edition. Mosby 2004.
Sternberg S. Diagnostic Surgical Pathology. Fourth Edition. Lipincott Williams and Wilkins 2004.
Robbins Pathologic Basis of Disease. Seventh Edition. WB Saunders 2005.
DeMay RM. The Art and Science of Cytopathology. Volume 1 and 2. ASCP Press. 1996.
Weedon D. Weedon's Skin Pathology Second Edition. Churchill Livingstone. 2002
Fitzpatrick's Dermatology in General Medicine. 6th Edition. McGraw-Hill. 2003.
Weiss SW and Goldblum JR. Enzinger and Weiss's Soft Tissue Tumors. Fourth Edition. Mosby 2001.
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