Vasoform Neoplasms and Other Lesions : Part II
Glomangiopericytoma (Sinonasal Type Hemangiopericytoma)
Introduction
Throughout our ENT surgical careers, we have listened to the tale of the highly controversial pericyte contractile cell adjacent to capillaries from our original pathology mentor, Professor Leslie Michaels, and subsequently from the next generation of pathologists, Dr. Andrew Gallimore and Dr. Ann Sandison. The addition of the solitary extrapleural fibrous tumor to the debate in the 1980s, which was originally thought to be a primary neoplasm of the pleura (first reported in 1931),1 has on many occasions during combined clinical pathology and radiology meetings caused us some confusion and has certainly been associated with considerable humor on occasions! We have fortunately worked long enough to see some clarification of these matters, and in 2005 the WHO classification of tumors2 finally allocated the term “glomangiopericytoma” to the sinonasal form of hemangiopericytoma. This tumor at present appears to be specific to the head and neck. In contrast to hemangiopericytomas and solitary fibrous tumors occurring elsewhere in the body (which now are recognized to have considerable overlap of their histological features and which are strongly CD34 positive, probably representing a specialist fibroblast), the glomangiopericytoma is negative for CD34 and positive for SMA, indicating a myopericytoma phenotype.
Definition
(ICD-O code 9150/1)
A sinonasal tumor demonstrating a perivascular myopericytoma phenotype.
Synonyms
As indicated above, the term sinonasal hemangiopericytoma has long been in use, but additionally hemangiopericytoma-like tumor, sinonasal glomus tumor, and simply hemangiopericytoma have all been used within the literature.
Etiology
There are no defined etiological factors.
Site and Incidence
Glomangiopericytomas have a predilection for the nasal cavity and paranasal sinuses but they remain a rare lesion comprising less than 0.5% of all neoplasms in this area. Catalano et al,3 presenting seven of their own patients in 1996, undertook a thorough review of the available literature and ascertained a total of 119 cases with sufficient evidence for sinonasal hemangiopericytoma. Over 150 cases have now been reported in the literature and we have treated 13 cases.
The majority of reported cases appeared to arise in the nasal cavity and many were noted to arise from the inferior or middle turbinate (Fig. 9.27). However, involvement of the ethmoids, sphenoid, maxillary, frontal sinuses, and nasopharynx have all been noted. The ethmoids and sphenoid are commoner than the maxillary or frontal sinuses. A small proportion of the tumors are bilateral. Extension through the cribriform plate into the intracranial structures can occur. Two of Catalano′s own seven cases had involved the cribriform plate.3 In our group, 7 arose in the nasal cavity, 2 the ethmoid sinuses (one breaching the skull base), and 4 originated in the orbit, specifically affecting the nasolacrimal sac. Within the nasal cavity both the lateral wall and septum were affected (Table 9.5).
Diagnostic Features
Clinical Features
The reported ages ranged from 4 to 80 years with an approximately equal distribution of males to females, although Catalano′s own series of seven cases had a female predominance of 6:1,3 as does ours with 9 women versus 4 men. Our patients also had a wide age range from 20 to 82 years, mean 59.6 years.
Nasal obstruction and epistaxis are the commonest non-specific presenting symptoms. Others include rhinorrhea, serous otitis media, proptosis, facial pain, and infraorbital paresthesia. On examination those tumors visible in the nasal cavity generally appear to be tan or gray colored polypoidal lesions that bleed briskly on manipulation.
Imaging
Imaging features are nonspecific showing nasal cavity or paranasal sinus lesions, which often have a significant polypoidal appearance with associated inflammatory changes in the dependant sinuses, bone erosion, and sclerosis (Fig. 9.27).
Histological Features and Differential Diagnosis
On histological evaluation, these lesions are subepithelial and well delineated but they are nonencapsulated cellular tumors that may surround other normal structures. Most tumors are highly cellular with short to mediumsized spindle cells that are tapered and without much cytoplasm, which helps to distinguish them from higher-grade lesions such as leiomyosarcoma and fibrosarcoma. The nucleoli are usually single and not prominent and chromatin is finely dispersed. The pattern is generally one of short fascicles, small whorls, and perpendicular orientation around vessels. Vascular channels vary from capillary size to large patchoulis spaces that may have a “stag horn” or antlerlike configuration. A prominent periepitheliomatous hyalinization is characteristic. Occasional mitotic figures may be present but necrosis is not found in these lesions. Associated extravasated erythrocytes, mast cells, and eosinophils are frequently present and occasionally giant cells may be seen.
Immunohistochemistry
As noted in the introduction to this section, glomangiopericytoma of the sinonasal tract is distinctly different from soft tissue hemangiopericytoma in the rest of the body and lacks the strong diffuse staining for CD34. Glomangiopericytomas usually have diffuse reactivity for actins, factor XIIIa, and vimentin. While for many years this lesion was known as a sinonasal hemangiopericytoma, it is clinically, morphologically and biologically distinct from other soft tissue type hemangiopericytomas.
Differential diagnosis includes hemangioma, solitary fibrous tumor, glomus tumor, leiomyoma, synovial sarcoma, leiomyosarcoma, fibrosarcoma, and malignant fibrous histiocytoma. Additionally, olfactory neuroblastoma, solid adenoid cystic carcinoma, angiofibroma, and carcinomas have been mentioned as possible areas of confusion in the past, but with modern immunohistochemistry and our increased understanding of this lesion, they should not present a problem in the future.
Treatment and Prognosis
Both the large reviews of cases by Catalano et al3 and Thompson et al4 stress that surgery was the treatment of choice for the majority of these patients. Provided that complete surgical excision appears to be achieved, they have greater than 90% 5-year survival. Recurrence has been reported in up to 30% of cases, but in the 104 cases reported from the files of the Armed Forces Institute of Pathology between 1970 and 1995 by Thompson and colleagues,4 the 18 recurrences developed over periods of between 1 and 12 years. Recurrent tumor can be managed by additional surgery and only 4 of their 104 cases were given additional radiotherapy. Of interest in this particular paper by three internationally eminent pathologists—Lester Thompson, Markkus Miettinen, and Bruce Wenig—is the considerable debate that they undertake in this paper over the biological behavior of these sinonasal tract lesions, and their statement that their preferred terminology for this tumor was sinonasal type hemangiopericytoma. Less than 2 years later it was listed in the WHO classification as glomangiopericytoma! Their detailed histopathological and immunohistochemistry studies did not shed light on the small number of recurrences but did confirm the relatively indolent behavior with a potential for local recurrence but not metastatic disease. They concluded that the evaluation demonstrated a kinship to glomus tumors, reporting the contention that sinonasal type hemangiopericytoma is a perivascular tumor with myoid or glomus-like differentiation distinctly contrasting with the hemangiopericytoma of soft tissues.
As might be expected, endoscopic resection has been undertaken for this lesion and small numbers appear as single case reports5,6 or in the various series appearing in the literature,7 the largest of which is a retrospective review of 10 cases treated between 1997 and 2008.8 This comprised 5 men and 5 women with an average age of 59 years, one of whom had a stroke related to the surgery. However, only one patient had a recurrence that required combined external and endoscopic surgery together with orbital exenteration, and died of disease at 138 months.
In our series of 13 patients, treatment was surgical in all cases, only one receiving additional radiotherapy for recurrent disease. The surgical procedures ranged from intranasal ethmoidectomy in 1970 to endoscopic surgery for the four most recent cases (post 2000). One patient had a craniofacial resection for skull base involvement early in the series and five had lateral rhinotomy approaches to access either nasal or medial orbital lesions. In the orbit complete resection of the nasolacrimal system has been required together with the adjacent orbital periosteum and/or orbital clearance for the two most extensive lesions (Table 9.5).
Overall the results have been excellent, irrespective of the surgical approach, with 10 patients alive and well with long-term follow-up ranging from 2 to 22 years, one is alive with recurrence, one died of “old age” and the earliest patient was not followed up, having come from abroad. Our series concurs with the reported literature.
Key Points
The WHO classification now uses the term “glomangiopericytoma” instead of sinonasal hemangiopericytoma as it is clinically, morphologically and biologically distinct from hemangiopericytomas in the rest of the body.
On immunohistochemistry glomangiopericytoma lacks the strong diffuse staining for CD34.
Complete surgical excision is treatment of choice by whatever approach is appropriate.
References
1. Klemperer P, Rabin C. Primary neoplasms of the pleura: A report of five cases. Arch Pathol (Chic) 1931;11:385–412 2. Barnes L, Everson J, Reicchart P, Sidransky D, eds. World Health Organization Classification of Tumours. Pathology and Genetics of Head and Neck Tumours. Lyon: IARC Press; 2005 3. Catalano PJ, Brandwein M, Shah DK, Urken ML, Lawson W, Biller HF. Sinonasal hemangiopericytomas: a clinicopathologic and immunohistochemical study of seven cases. Head Neck 1996;18(1):42–53 4. Thompson LD, Miettinen M, Wenig BM. Sinonasal-type hemangiopericytoma: a clinicopathologic and immunophenotypic analysis of 104 cases showing perivascular myoid differentiation. Am J Surg Pathol 2003; 27(6):737–749 5. Serrano E, Coste A, Percodani J, Hervé S, Brugel L. Endoscopic sinus surgery for sinonasal haemangiopericytomas. J Laryngol Otol 2002;116(11):951–954 6. Schatton R, Golusinski W, Wielgosz R, Lamprecht J. Endonasal resection of a sinonasal haemangiopericytoma. Rep Pract Oncol Radiother 2005;10:261–264 7. Kassam AB, Prevedello DM, Carrau RL, et al. Endoscopic endonasal skull base surgery: analysis of complications in the authors’ initial 800 patients. J Neurosurg 2011; 114(6):1544–1568 8. Bignami M, Dallan I, Battaglia P, Lenzi R, Pistochini A, Castelnuovo P. Endoscopic, endonasal management of sinonasal haemangiopericytoma: 12-year experience. J Laryngol Otol 2010;124(11):1178–1182Angiosarcoma
Definition
(ICD-O code 9120/3)
Angiosarcomas are rare, highly malignant tumors of vascular phenotype with anastomosing vascular channels lined with remarkably atypical endothelial cells.
Synonyms
Alternative names for these tumors include malignant hemangioendothelioma, malignant angioendothelioma, hemangiosarcoma, and lymphangiosarcoma.
Etiology
It is now generally accepted that there are five variants of angiosarcoma: (1) lymphedema angiosarcoma, first reported by Stewart and Treves in 19481; (2) post-mastectomy angiosarcoma2,3; (3) breast angiosarcoma; (4) deep soft tissue angiosarcoma; and (5) cutaneous angiosarcoma. Only the last two forms of angiosarcoma occur in the head and neck, and the scalp is by far the most common site for cutaneous angiosarcoma although the tongue, oral cavity, oropharynx, nasopharynx, sinonasal tract, and larynx may all be involved.4–7 While no specific etiological factors are known at a cellular level, angiosarcoma has also been reported to occur following administration of Thorotrast and following radiotherapy.8,9 Cytogenetic studies of angiosarcoma have not shown any consistent recurrent chromosomal abnormalities but typically complex karyotypes. TP53 mutational inactivation and an increase of MDM2 expression have been reported to lead to upregulation of VEGF expression in up to 80% of angiosarcomas.10,11
Site and Incidence
Angiosarcomas most commonly arise in the skin and superficial soft tissues of the head and neck but the disease is rare, accounting for less than 2% of all sarcomas. More than half of all angiosarcomas occur in the head and neck. The scalp, forehead, and face—in descending order—are by far the commonest sites in the larger reported series.6,12
In the sinonasal tract, the maxillary sinus is the most frequently reported site of origin, although as the nasal cavity and other paranasal sinuses are frequently involved as well at the time of presentation, the exact site of origin is not always clearly defined. Of the combined total of 43 cases from two reports emanating from major head and neck centers in the United States, only two cases involved the nose and sinuses, one each involving the ethmoid and maxilla. A recent report by Nelson and Thompson presented 10 cases of sinonasal tract angiosarcoma that were retrospectively retrieved from the Otorhinolaryngologic Registry of the Armed Forces Institute of Pathology.13
Diagnostic Features
Clinical Features
Angiosarcomas can occur at all ages, from infants to the elderly, but predominate in the latter group. Those reported from the sinonasal tract appear to have a peak in the fifth decade and a notable male predilection of between 2:1 and 3:1. The female patients tend to be approximately a decade younger in the reported cases.14–16 This said, our single case of angiosarcoma occurred in a 58-year-old woman from Cyprus whose tumor arose in the middle meatus, affecting the middle turbinate and anterior ethmoids without obvious orbital involvement.
Elderly male patients predominate in reports with lesions presenting in the sinonasal tract in the same way as the much commoner presentation of the skin and soft tissues of the scalp and face. The duration of symptoms reported in the sinonasal cases seems to vary from weeks to months but is generally shorter than many of the cases affecting areas of skin. The latter often remain incorrectly diagnosed for long periods of time and have been reported to be confused with diagnosis such as rhinophyma, arteriovenous malformations, lymphoma, sarcoidosis, or facial granuloma. Sinonasal cases, however, commonly present with recurrent epistaxis and an intranasal/sinus mass lesion, nasal obstruction, nasal discharge (which has often been described as foul smelling and blood tinged), paresthesia, facial pain, and dental symptoms. In contrast again to the commoner skin lesions, lymph node involvement and distant metastases are not common at presentation of the sinonasal lesions.
Tumors present with a mean size of around 4 cm in the sinonasal area but may be considerably larger and have been described as red to purple, soft and friable, but additionally nodular or polypoidal and often ulcerated with associated hemorrhage, blood clot, and notable areas of necrosis.
Imaging
Angiosarcomas presenting in the sinonasal tract have nonspecific imaging appearances and, despite being highly anaplastic vasoformative lesions, they do not usually have sufficiently large vascular channels or spaces for them to be clearly demonstrated either on CT or MRI. The value of imaging is related more to defining the extent of the lesion, although the lesions may be diffuse and infiltrative, giving rise to an underevaluation of their true extent.
Histological Features
Nelson and Thompson′s study of 10 cases of sinonasal tract angiosarcomas showed that all tumors had anastomosing vascular channels lined with notably atypical endothelial cells that protrude into the lumen.13 The vascular channels appear to dissect the stroma and there are both capillary-sized vessels and more cavernous vascular spaces. The endothelial cells vary considerably from being somewhat flattened to spindle and epithelioid types that may form papillary tufts. Neolumen formation is common and there are often considerable numbers of atypical mitotic figures. There are notable areas of necrosis and hemorrhage, and immunohistochemistry shows them to be immunoreactive for CD34, CD31, factor VIII, R-Ag, and smooth muscle actin. They are generally nonreactive for keratin and S100 protein.
Differential Diagnosis
The rarity of these lesions has presented considerable problems in the past as the differential diagnosis includes a wide range of possibilities ranging from granulation tissue through intravascular capillary endothelial hyperplasia, hemangioma, angiofibroma, and glomangiopericytoma, to poorly differentiated neoplasms including malignant melanoma, carcinoma, large cell lymphoma, and Kaposi′s sarcoma.
CD31 reactivity and negativity for epithelial membrane antigen, S100 protein, and melanoma markers help to distinguish angiosarcoma from other tumor types and the infiltrative growth pattern, mitotic activity, and marked atypia help to distinguish angiosarcoma from benign vascular tumors. Unfortunately, the reports of these rare lesions confirm the difficulties experienced with the differential diagnosis in many cases and the consequences of this are inadequate or inappropriate treatment. As angiosarcomas have a poor prognosis, it is particularly appropriate to distinguish them from other possible conditions.
Treatment and Prognosis
Virtually all reported patients have been treated by surgical resection with postoperative radiation and, more recently, variable amounts of additional chemotherapy. Nelson and Thompson′s 10 sinonasal cases were all treated by surgery with postoperative radiation, but 6 died from disease with a mean survival of 28.8 months.13 Two further patients died without evidence of disease with a mean of 267 months and 2 remained alive with no evidence of disease at last follow-up with a mean of 254 months. So while recurrences appear to occur in more than 50% of patients, most likely due to incomplete excision or possibly multifocal areas of the lesions, several authors have stated that nasal angiosarcoma appears to have a better prognosis than the commoner scalp and facial skin lesions. There is insufficient literature to know whether this is due to most sinonasal angiosarcomas being described as histologically relatively low grade or a consequence of a shorter interval between diagnosis and treatment. Different survival rates may be related to different treatment, although most reports agree that the outcome is more favorable with the smaller-sized cutaneous and soft tissue lesions.17,18 Lymph node and distant metastases seem to be uncommon in the reports of sinonasal cases, supporting the potential for a better prognosis.19 Our patient underwent a wide-field clearance via a lateral rhinotomy in 1995 following failed chemoradiotherapy in Cyprus. She remained disease-free for 3 years until lost to follow-up.
Kaposi′s sarcoma
Definition
(ICD-O code 9140/3)
Kaposi′s sarcoma (KS) is an angioproliferative lesion that is regarded as one of the commonest variants of angiosarcoma. It was first recognized by Moritz Kaposi in 187220 and reported in Africa in the 1940s.21 In 1972 it was described after renal transplantation and in the early 1980s was reported in New York and Los Angeles in association with HIV infection.21
Thus Kaposi′s sarcoma is classified into four main forms: (1) classic, (2) African endemic, (3) immunosuppression- or transplantation-associated, and (4) AIDS-associated22 of which type 4 is most commonly encountered in the upper respiratory tract. A further variant has been recently described in HIV-negative men.23
Etiology
Kaposi′s sarcoma is now known to occur secondarily to infection with human herpes virus (HHV)-8 24,25 and the mode of transmission is mainly via saliva.26 HHV-8 has been found in 49 to 100% of KS-affected patients. HHV-8 has been shown to replicate in oropharyngeal cells.
Incidence and Site
The AIDS-associated form is commonly found in the upper respiratory tract, especially in the oral cavity, although the other forms are rather rare in the head and neck.27
Where antiretroviral therapy has been available there has been a decrease in KS in Europe and the United States but it is increasing in Africa.28 A 20-fold increase has been reported, composed of both African endemic and HIV-associated KS and is affecting men, women, and children.29 In Zimbabwe, KS is the commonest cancer in men, with the age-standardized rate of KS between 1993 and 1995 being 47.2/100,000 for men and 17.3/100,000 for women.28
Diagnostic Features
Clinical Features and Histology
While classic KS typically affects elderly men, as a consequence of the association with HIV the demographic of KS in the head and neck is most often young to middle-aged males. However, as mentioned above, women and children can also be affected.
A wide variety of presentations have been described but the commonest appearances are of a patch (early) or nodular violaceous (late) lesion on the skin or mucosa. These are most often seen in the oral cavity, particularly on the hard palate and gingivae. The lesions may occasionally affect the nasal cavity and maxilla with or without AIDS and often in cases of disseminated disease.30–33 The lesions may be single or multiple and are not painful. As they are superficial lesions, the imaging appearances are minor.
At the outset they are nonspecific proliferations of vascular tissue but become more infiltrative with time, developing nodularity. At this stage they are composed of spindle cells together with evidence of neoangiogenesis, inflammation, and edema. KS must therefore be differentiated from other tumors such as fibrosarcoma and kaposiform hemangioendothelioma, a lesion that is more typically seen in the retroperitoneum and limbs in children.34 However, an array of immunohistochemistry markers are needed to show positivity to endothelial antigens (CD31, CD34) and factor VIII-related antigen as well as immuno-reactivity to HHV-8.22 The lesions are also usually positive to vimentin, LYVE-1, VEGFR-2 and -3 (vascular endothelial growth factor), angiopoietin-2, and D2–40.
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
