Nasopharyngeal Angiofibroma
Epidemiology
Juvenile
nasopharyngeal angiofibroma (JNPA) is found more frequently in young pubertal
boys (288); it has been shown to contain androgen receptors (4,81) and
occasionally to regress with estrogen therapy. Hwang et al. (125), in 24
nasopharyngeal angiofibromas, detected androgen receptors in 18/24 (75%) cases,
whereas only two (8.3%) were positive to progesterone. None of the 24 cases was
positive for antibodies to estrogen.
JNPA
comprises <0.05% of head and neck tumors (168). Patient age at presentation
ranges from 9 to 30 years (52,272,288), with a median of 15 years. Females comprise
<4% of the total cases (52). Some investigators have suggested chromosomal
studies in affected women because this is mainly a male disease (39).
The tumor
is believed to originate from the posterolateral wall of the nasal cavity where
the sphenoidal process of the palatine bone meets the horizontal ala of the
vomer and the roof of the pterygoid process (4) because it is always involved
(39). Other investigators agree, because involution of tumor after irradiation
usually occurs in this direction (235).
Clinical
Presentation and Pathology
Symptoms
usually occur 2 to 48 months before diagnosis (52). The most common complaints
are nasal obstruction or epistaxis, followed by nasal voice or discharge, cheek
swelling, proptosis, diplopia, hearing loss, and headaches (52). In a series
byWitt et al. (288), 7/31 patients presented with anomalous sexual development.
Nasopharyngeal
angiofibroma may initially extend into the nasal fossae and maxillary antrum
and push the soft palate downward, then through the pterygopalatine fossa and
superoanteriorly through the inferior orbital fissure or laterally through the
pterygomaxillary fissure to the cheek and temporal regions (58).
Beham et
al. (15) reported on 32 cases of nasopharyngeal angiofibroma. Most of the tumor
vessels, which lacked elastic laminae, were characterized by vascular walls of
irregular thickness and variable muscle content. In places endothelial cells
were separated from the stroma by only a single attenuated layer of contractile
cells, in some more fibrotic hyaline areas, the stromal cells displayed
reactivity for smooth muscle actin. The irregularity of the vascular walls,
together with the lack of elastic laminae and stromal fibers, explains the
pronounced tendency for hemorrhage in these lesions.
Differential
diagnosis includes fibrosarcoma, rhabdomyosarcoma, chronic sinusitis,
arteriovenous malformation, lymphangioma, neurofibroma, pleomorphic adenoma,
lymphoma, pyogenic granuloma, polyps, and hemangioma.
Diagnostic
Work-Up
After the
history and physical examination, CT scans with and without contrast should be
obtained. The pattern of enhancement in this highly vascular tumor is
diagnostic (164,192), and many investigators believe carotid angiograms are
unnecessary (30) after CT diagnosis of the lesion, unless embolization, which
is also controversial, is contemplated.
CT scans
are especially helpful in regions involving thin bony structures (paranasal
sinuses, orbits), where CT performs better than MRI. In the nasopharynx and
parapharyngeal space MRI is superior to CT. Obtaining tumor volumetric data
with spiral CT or MRI facilitates 3D treatment planning (102).
Seventy-two
patients with JNPA were evaluated with CT and/or MRI (164). Origin of the tumor
was in the pterygopalatine fossa at the aperture of the pterygoid (vidian)
canal. The tumor extended posteriorly along the pterygoid canal with invasion
of the cancellous bone of the pterygoid base and greater wing of the sphenoid
in 60% of the patients. The inability to remove the tumor in toto was
principally due to deep invasion of the sphenoid; 93% of recurrences occurred
with this type of tumor extension.
If
intracranial extension is noted and radiation therapy is contemplated, no
further studies are indicated. If the lesion is extracranial and surgery is
indicated, bilateral carotid angiograms will identify the feeding vessels and
delineate the boundaries of the tumor (Fig. 45.13).
Biopsies
are not indicated in all patients because of the potential for severe
hemorrhage. It is important to perform a biopsy of the lesion when the clinical
picture (sex, age, location, and behavior of the lesion) is not consistent with
JNPA (250) because some lesions have proven to be sarcomas or chronic sinusitis
(39). Two cases of fibrosarcoma have been reported in patients in their 40s
(66).
Staging and
Prognostic Factors
Two staging
schemes have been proposed: (a) the system of Chandler et al. (39) (Table
45.14), and (b) a radiographic staging system by Sessions et al. (235). Stage
Ia is limited to the nasopharynx and posterior nares; stage Ib extends to the
paranasal sinuses; stages IIa, IIb, and IIc extend to other extracranial
locations; and stage III is intracranial.
Table
45.14. Staging of Nasopharyngeal Angiofibromas
In a
retrospective review of 44 cases of juvenile nasopharyngeal angiofibroma,
invasion of the skull affected two thirds of the patients, and the rate of
recurrence was 27.5% (116). Extensions to the intratemporal fossa, sphenoid
sinus, base of pterygoids and clivus, the cavernous sinus (medial), foramen
lacerum, and anterior fossa were correlated with more frequent recurrence.
Long-term radiographic follow-up showed residual disease in nine asymptomatic
patients: these remnants gradually involuted.
General
Management
The
decision of whether surgery or radiation therapy should be used depends in part
on the initial extent of the disease. In patients with extracranial tumors
(116,288), surgery is the treatment of choice and yields near-zero mortality or
any longterm morbidity.
Tumor remnants
in symptomfree patients should be kept under surveillance by repeated CT
scanning, since involution may occur. Recurrent symptoms may be treated by
radiation therapy rather than by extended surgery or combined procedures
(39,61,116).
When there
is intracranial tumor extension (seen in about 20% of patients) (130,288), the
risk of surgically related death increases. In a literature review by Jones et
al. (133), it was found to be 14% to 84%. Most of these patients are best
treated with irradiation (54).
Some
investigators recommend preoperative intraarterial tumor vessel embolization at
the time of diagnostic bilateral carotid angiography, claiming a decrease in
operative bleeding (154). Salvage with embolization of polyvinyl alcohol has
been described (129). Others have reported anecdotal evidence of partial
regression with the use of estrogens, believed to be the result of feedback
inhibition of the pituitary's production of gonadotropin-releasing hormone.
Although
radiation therapy is equally effective in extracranial tumors, the low but
existing risk of secondary malignancies should limit its use to the most
advanced tumors only (10,154,284). In the experience of Cummings et al. (54)
covering 20 years, only two radiation-related malignancies were noted (one
skin, one thyroid).
Radiation
Therapy Techniques
Photon
irradiation should be used for these patients, and fields must be
individualized to cover the tumor completely with a margin (1 to 2 cm).
Treatment portals are similar to those used in carcinoma of the nasopharynx
(without irradiating the cervical lymph nodes) or carcinoma of the paranasal
sinuses when these structures or the nasal cavity is involved. Opposing lateral
portals are suitable in most patients, with larger fields and compensators used
for tumors extending into the nose (Fig. 45.14). More extensive disease
requires three-field or wedge-pair arrangements of 3DCRT or IMRT that can yield
excellent dose distributions, particularly when there is nasopharyngeal or
intracranial tumor extension. In all cases the eyes are protected asmuch as
possible. The recommended tumor dose ranges from 30 Gy in 15 fractions in 3
weeks to 50 Gy in 24 to 28 fractions in 5 weeks (54). A conventional setup uses
6- to 18-MV photons to treat the lesion with parallel-opposed fields to 50 Gy
(2-Gy fractions) (Fig. 45.15).
Figure
45.14. Diagrams of the most commonly used conventional field arrangements for
treatment of nasopharynx angiofibroma: lateral opposed field pair and
three-field technique.
Figure 45.15.
Example of conventional lateral portal used at the Mallinckrodt Institute of
Radiology for nasopharyngeal angiofibroma.
The
advantages of IMRT for the treatment of extensive and/or recurrent JNPA has
been described in three patients on whom the tumor affected the base of skull,
pterygopalatine, and intratemporal fossae, posterior orbit, and nasopharynx
(151). Tumor dose varied from 34 to 45 Gy. The tumor shrunk radiographically in
all three cases, and there was no endoscopic evidence of disease in two cases
at 15 months and 40 months. Late toxicity was limited to one episode of
epistaxis and persistent rhinitis in one patient.
Results of
Therapy
Jones et
al. (133) reported the results of 40 patients with JNPA treated with surgery
alone. With a mean follow-up of 17 months (6 to 36 months), the control rates
according to the Sessions staging system were as follows: 100% (stages I and
IIa), 83% (stage IIb), 80% (stage IIc), and 50% (stage III). All failures were
controlled with irradiation (n = 18 patients), embolization (n = 8), or
surgical resection (n = 8), and the other four were observed only,
demonstrating the extremely high salvage rate in this disease (126). These
findings are consistent with other series reporting initial surgical control of
86% with an ultimate control rate of 96% (288).
In another
report, 18 patients were treated with gross tumor excision; two cases with
intracranial involvement required a combined neurosurgical-otolaryngologic
approach (61). Recurrent intracranial disease was detected by MRI in three
patients, who were treated with 35-, 36-, and 45-Gy external-beam irradiation.
Extracranial tumor recurrences were re-excised in seven patients. All patients
(followed up with serial MRI) are living without evidence of active disease.
Cummings et
al. (54) treated 42 patients primarily with irradiation and 13 for postsurgical
failures; all except six had biopsies. Nine had stage IV disease according to
Chandler's staging system. Dose was 30 to 35 Gy in 14 to 16 fractions over a
3-week period. Follow-up ranged from 3 to 26 years. The control rate was 80%
and was equivalent for all dose ranges. Local control was 89% and 74%,
respectively, when three fields versus two fields were used. When the field
size was more than 6 by 6 cm, the control rate was 83% versus 55% for smaller
portals, indicating the importance of accurately determining the target volume,
including any potential tumor extension. Of 11 recurrences, eight were
controlled by a second course of irradiation and three by surgery. These tumors
regress slowly, with 50% still present at 12 months. At 24 months, 23% of
tumors were still present, and half of those recurred. Of the complete
responders, only 1/33 had a recurrence. Robinson et al. (224) also found that
objective responses after irradiation were noted within 6 months in 60% of
patients and within 6 to 20 months in the other 40%. Symptoms, however,
resolved in all patients within 6 months of treatment.
At the
Mallinckrodt Institute of Radiology, Fields (written communication, 1989)
reviewed our experience with 13 patients: 11 surgical failures and two
primarily treated with irradiation. Intracranial extension was noted in 38% of
patients. Follow-up ranged from 40 to 173 months. Doses ranged from 36 to 52
Gy, with a median of 48 Gy (1.8 to 2 Gy per fraction, 5 days a week). The
control rate was 85%; patients failing irradiation were salvaged with
embolization. Late morbidity was mostly xerostomia and dental decay.
Ungkanont
et al. (272) described results in 20 patients treated before 1974 and 23
treated between 1975 and 1993: 31 had surgery (18 with preoperative
embolization), three had irradiation, seven received chemotherapy (four
combined with surgery), and two were observed. Diseasefree survival was 67%;
28% of patients survived with residual tumor, and 4.6% died of surgical
complications.
Tumor
regression usually occurs slowly after either irradiation (54,172) or
chemotherapy (100); therefore, the presence of tumor up to 2 years after
treatment is not an invariable sign of failure unless it is symptomatic or
progressing.
The
management of large JNPA with intracranial extension is difficult. In 18
patients with JNPA, preoperative MRI, embolization of feeding branches from the
external carotid artery, and attempted complete resection were used in seven
patients with intracranial disease (61); serial MRI scans were used for
follow-up. Intracranial disease that was persistent or recurrent and
demonstrated subsequent growth was irradiated (35 to 45 Gy) or re-excised.
Wiatrak et
al. (284) reported on three patients with extensive intracranial extension
treated primarily with radiation therapy doses of 36.6, 40, and 50.4 Gy,
respectively, without surgical tumor resection. Although there was no complete
resolution of the tumors, significant improvement of symptoms was obtained
without serious sequelae. Malignant degeneration in JNPA undergoing radiation
therapy has been occasionally reported (16,54,224).
Goepfert et
al. (100) reported on five patients with aggressive nasopharyngeal
angiofibromas recurrent after extracranial resection and irradiation who were
treated with chemotherapy. Doxorubicin (60 mg/m2 intravenous [IV] push for 1
day) and dacarbazine (250 mg/m2 IV drip for 5 days) were given, with courses
being repeated every 3 to 4 weeks. In a second regimen, vincristine,
dactinomycin, and cyclophosphamide were administered at usual doses. Excellent
tumor regression was noted in all patients. Patients were disease free at 2, 3,
6, and 10 years.
Ochoa-Carrillo
et al. (192) reported on 31 patients treated with surgery and/or radiation
therapy. Surgery was the treatment chosen in patients with stage II and III
disease, while radiation therapy was the treatment in stage IV, but it had low
effectiveness, indicating the need to carefully investigate the value of
craniofacial approaches in these tumors. Radiation therapy (30 to 55 Gy) was
administered to 16 patients; seven with stage III persistent or recurrent
tumor, and eight patients as initial treatment for stage IV disease. The diseasefree
interval of patients with stage III and IV disease was 80.3% and 19%,
respectively, after 36 months of follow-up.
Tranbahuy
et al. (267) reported on seven patients with juvenile angiofibroma who
underwent direct tumoral embolization. This technique induced marked
devascularization and necrosis of the tumor. No neurologic sequelae were
encountered.
Sequelae of
Therapy
Most
investigators agree that surgical mortality increases with intracranial
extension of the tumor. The most common radiation therapy sequelae include
delayed growth secondary to hypopituitarism and decreased bone maturation (39).
There are several well-documented cases of radiation-induced sarcomas in these
patients (54,245) with doses ranging from 66 Gy to more than 90 Gy. Spagnolo et
al. (245) reported on four patients treated with irradiation who later
developed sarcoma. Chen and Bauer (44) reported the same findings in a patient
receiving 66 Gy and followed up for 18 years. This patient was 48 years of age,
so the original diagnosis of JNPA does not coincide clinically with typical
JNPA. Cummings et al. (54) reported two neoplasms developing 13 and 14 years
after irradiation; one was a basal cell carcinoma and one metastatic thyroid
carcinoma. Both patients are alive without disease. Two patients developed
cataracts.
Extracranial Meningiomas
Extracranial
meningiomas of the sinonasal tract are rare tumors (264). The overall prognosis
is good, without a difference in outcome between benign and atypical
meningiomas. Thirty cases of sinonasal tract meningiomas were retrieved from
the files of the Otorhinolaryngic Registry of the Armed Forces Institute of
Pathology (15 females and 15 males, aged 13 to 88 years [mean 47.5 years])
(264). Patients presented clinically with a mass, epistaxis, sinusitis, pain,
visual changes, or nasal obstruction, dependent on the anatomic site of
involvement. Symptoms were present for an average of 31.3 months. The tumors
affected the nasal cavity (n = 14), nasopharynx (n = 3), frontal sinus (n = 2),
sphenoid sinus (n = 2), or a combination of the nasal cavity and ethmoid,
frontal, sphenoid, and/or maxillary sinuses (n = 9). Tumors size ranged from 1
to 8 cm (mean, 3.5 cm). Radiographic studies demonstrated a central nervous
system connection in six cases; the tumors often eroded the bones of the
sinuses (n = 18) and involved the surrounding soft tissues, the orbit, and
occasionally the base of the skull. Histologically, the tumors demonstrated
features similar to intracranial meningiomas; the majority of the
meningothelial type (n = 23), although there were three atypical meningiomas.
Immunohistochemical studies confirmed the diagnosis with reactions for
epithelial membrane antigen and vimentin (all tested). The differential
diagnosis included paraganglioma, carcinoma, melanoma, psammomatoid ossifying
fibroma, and angiofibroma.
Surgical
excision was used in all patients. Three patients died with recurrent disease
(mean, 1.2 years), one was alive with recurrent disease (25.6 years), and the
remaining 24 patients were alive or had died of unrelated causes (mean, 13.9
years) at the time of last follow-up (two patients were lost to follow-up).
Nonlentiginous Melanoma
Malignant
melanoma accounts for 11% of primary head and neck malignancies (8). Of all
malignant melanomas, 20% to 35% are located in the head and neck area (108).
Cutaneous
Melanomas
In a review
of the literature, Batsakis (11) found that, of all head and neck malignant
melanomas, 64% to 78% were cutaneous, 6% to 8% were mucosal, and 14% to 30% were
ocular. The superficial spreading and nodular types of malignant melanoma have
a metastatic potential of 10% to 30% and 50%, respectively (108). Neurotropic
melanoma is an uncommon variant of cutaneous melanoma, with a higher propensity
to invade peripheral nerves. A thorough evaluation with CT scans should
determine if there is intracranial or base of the skull involvement; Beenken et
al. (14) reported on 13 such patients, two of whom failed perineurally.
Treatment
of cutaneous melanomas has typically been wide excision of the lesion with a
minimum 3-cm margin (8). More recently, margins of at least 2 cmhave been used
in the head and neck area compared with wider margins for stage Imelanomas,
with equivalent success as noted by the local failure rate of 3% to 6% (155).
The
Princess Margaret Hospital treated 16 patients with nodular melanomas with
local excision and postoperative radiation therapy (50 Gy in 10 fractions over
2 weeks); 14 exhibited local tumor control, and six were alive and well 2 to 14
years after treatment. These results were comparable with those with wide local
excision alone but with less morbidity and fewer cosmetic alterations. Later,
at the same institution, Harwood and Cummings (108) treated five patients with
definitive radiation therapy for superficial spreading melanoma of the head and
neck area. All five lesions were locally controlled; one patient had a lymph
node metastasis that was later controlled, and one died of distant metastases.
They recommend treating these patients with 45 Gy in 10 fractions over 2 weeks
to 50 Gy in 15 fractions in 3 weeks (107,111).
Harwood and
Cummings (108) also reported results in 74 patients treated with three 8-Gy
fractions given on days 0, 7, and 21 with shielding of the spinal cord, brain,
and eye. Thirty patients were treated postoperatively after neck dissections if
they had extracapsular extension, multiple nodal involvement, a node >3 cm,
or residual disease. Tumor control in the neck was achieved in 26/30 patients
(86.6%) with follow-up of 1 to 4 years. In four patients with microscopic
residual disease at the primary site, this postoperative regimen controlled
three of four lesions with follow-up of 1 to 3.5 years. The other 40 patients
were treated either for gross (13 patients) or recurrent (27 patients)
cutaneous melanoma. Complete response was observed in 15/40 lesions (37.5%) and
partial response in 12. An update of Harwood's data (personal communication,
1989) showed a neck tumor control rate of 94% in 41 adjuvantly treated patients
versus 57% in 48 patients with gross residual or recurrent tumors. He concluded
that irradiation alone should be considered for treatment of superficial
spreading melanomas when surgery is contraindicated or after a simple excision
in all cases of nodular melanoma in which a wide excision may be
contraindicated because of age, location, or medical condition. For nodal
disease, patients with poor prognostic pathologic factors should receive
postoperative irradiation. Recurrent or unresectable tumors also should be
irradiated. He recommended high-dose fractions because the local control rate
was 71% when the dose per fraction was >4 Gy and 25% with lower fractions
(111).
Another
approach to the treatment of recurrent or unresectable cutaneous melanomas is
combined hyperthermia and high-fraction radiation therapy as reported by Emami
et al. (76). The data support the use of high fractions for melanoma because
Overgaard's complete response rate was 59% when fractions of more than 4 Gy
were used and 33% for lower dose per fraction sizes. However, a randomized
study by the Radiation Therapy Oncology Group comparing four fractions of 8 Gy
given on days 0, 7, 14, and 21 and 20 fractions of 2.5 Gy in 5 weekly fractions
showed no significant difference in tumor response (24.2% and 23.4% complete
response and 35% partial response) (218).
Mucosal
Melanomas
Primary
mucosal melanomas of the head and neck area comprise 2% to 8% of the cases seen
each year in the United States (13). They occur more commonly in countries such
as Japan, where mucosal melanoma is found in 22% to 32% of patients with
malignant melanoma (271). Most occur in the fifth to seventh decades of life;
they are extremely rare in the first two decades (0.6% of mucosal melanomas)
(91,269,270). The maleto-female ratio approaches 1:1 (269). A review by
Batsakis et al. (13) of 204 mucosal melanomas showed 56.4% to be from the upper
respiratory tract and 44% from the oral cavity and pharynx. Nasal
cavity/paranasal tumors comprise <1% of malignant melanomas and 2% to 9% of
head and neck melanomas (91,120). Pigmentation may precede the lesion in up to
28% of patients for more than 1 year (32). In the oral cavity, the most common
location is the hard palate (up to 80%), followed in order of decreasing
frequency by the upper gingiva and lower gingiva.
Diagnostic
Work-Up
An
excisional biopsy should be performed when feasible because some reports have
suggested possible local or metastatic spread secondary to a punch or
incisional biopsy (219), although this has not been noted in cutaneous
melanomas (103). Batsakis et al. (13) found that one third of these lesions
were amelanotic, and Hoki et al. (120) noted that 25% were amelanotic.
Metastatic
melanoma to the mucosa of the head and neck area is less common (115). It can
be differentiated from primary tumors by the presence of normal tissue between
subepidermal tumor and the basal layer of melanocytes (13). In a review of the
literature. The larynx, tongue, and tonsils are the most common locations for
metastases (115).
Prognostic
Factors
Batsakis et
al. (13) found >0.5 mm invasion to be a poor prognostic factor. Trapp et al.
(268) noted this to be true only in patients with more than 0.7 mm invasion.
Lymph node involvement is not a prognostic factor. Mucosal melanomas fare worse
than their cutaneous counterparts (137), suggesting a lack of immunologic
competence (136,222).
Management
and Results of Therapy
In a review
of the Japanese literature, Umeda et al. (271) found a local tumor control rate
for stage I and II disease of 58% (7/12) in surgically treated patients with
oral melanomas and a minimum follow-up of 3 years. Similar rates of failure
have been reported, even with radical en bloc excisions (20% to 42%). Because
the main cause of treatment failure is distant metastases and because almost no
patient has clinically evident nodal metastases at presentation, an elective
neck node dissection is not recommended by some investigators (27). This
subject is still controversial because 30% to 60% of patients may later develop
nodal disease (23).
Ohya et al.
(195) treated six patients with oral cavity melanomas with irradiation as a
component of therapy (dose range 2,000 R to 8,900 R, five treated
preoperatively, one postoperatively). All lesions were locally controlled with
follow-up of 25 to 109 months; 3/7 patients were alive with 4 to 5 years of
follow-up. Harwood and Cummings (108) treated 12 cases and added 12 cases from
the literature for a total of 24 patients and 25 lesions. Local tumor control
was achieved in 11/24 (9 to 54 months' follow-up). Six of seven tumors treated
with 4-Gy fractions or larger were controlled, versus 5/18 treated with smaller
fractions.
Postoperative
radiation therapy was reported by Panje and Moran (203). Five patients were
treated with 60Co or 4-MV photons, 50 to 60 Gy, 1.5 to 2 Gy per fraction, over
a period of 5 to 6 weeks. Only one patient showed local control; the other
patients failed 6 to 12 months after irradiation.
Kingdom and
Kaplan (140) described results in 13 patients with mucosal melanoma of the
nasal cavity and paranasal sinuses treated with surgical resection. Eight had
microscopically negative margins. Seven patients received postoperative
irradiation (30 to 62 Gy). The neck was treated in three patients with doses of
30 to 50 Gy. The local tumor recurrence rate was 85% (11/13), with a mean
interval from primary tumor treatment to recurrence of 16 months. Metastatic
neck disease developed in two patients and distant metastases in four. Patients
receiving postoperative irradiation had increased diseasefree interval and
prolonged survival. Negative surgical margins were not predictive of a more
favorable outcome. The investigators recommend resection of tumor with negative
margins and postoperative irradiation for the treatment of all patients with
mucosal malignant melanoma.
Patients
with nasal cavity/paranasal mucosal melanoma have a median survival of 24
months. Five-year diseasefree survival rates of 25% have been reported (269).
Patients with laryngeal melanoma had a 13% 5-year diseasefree survival rate
(137). Because of the poor results obtained and because 37% of patients had
associated adjacent pigmentation (222), some investigators recommend
prophylactic excision of all melanocytic nevi. Because the results with irradiation
are comparable with those of surgical series and because of the poor survival
of these patients due to distant metastases and not locoregional failure,
irradiation alone, with surgery for salvage, should be seriously considered as
the primary treatment for mucosal melanomas of the head and neck (111)
Lentigo Maligna Melanoma
Natural
History
Lentigo
maligna (Hutchinson's melanotic freckle [124] or circumscribed precancerous
melanosis of Dubreuilh) and its invasive counterpart, lentigo maligna melanoma
(LMM), are well-recognized clinicopathologic entities (46). LMM comprises about
10% of all melanomas in the head and neck, occurs predominantly on the face and
ears of elderly persons, and generally has a very long natural history,
frequently reaching a large size before diagnosis. Approximately one third of
lentigo maligna lesions, if left untreated, will eventually transform into
invasive LMM.
Tannous et
al. (260) hypothesized that lentigo maligna can be divided into two categories:
one represents a pigmented lesion that is a precursor to melanoma, and the
other melanoma in situ. Also, they hypothesized that in some patients there is
a progression to malignant melanoma.
Clinical
Presentation and Diagnostic Work-Up
These
lesions appear as circumscribed and later as more diffuse areas of
hyperpigmentation of the skin. They may develop some superficial nodularity and
eventual ulceration as they become more invasive. In 10% of the latter
patients, regional and distant metastases eventually develop. The 10%
metastatic spread in LMM contrasts with the 25% metastatic tendency in nodular
melanomas arising in superficial spreading melanomas and a 50% metastatic
spread in nodular melanomas arising de novo.
The
diagnostic work-up of these patients is similar to that of patients suspected
of having malignant melanoma. Biopsies of the lesion are required to obtain
histopathologic confirmation of the diagnosis. Careful physical examination
must rule out any areas of extension or regional or distant spread.
General Management
The usual
treatment of lentigo maligna and LMM has been surgery, with approximately 1- to
2-cm margin of normal skin (8).
Hill and
Gramp (118) reported on 66 cases of lentigo malignant melanoma; 38% of which
required two excisions or more to clear the tumor and 32% of cases showed
evidence of invasive melanoma. Only one case has recurred thus far, and none
have developed metastatic disease.
Because of
the low incidence of regional lymph node metastases, elective lymph node
dissection is not indicated. For larger lesions, wider surgical excision with
skin grafting has been reported to give poor cosmetic results.
Cohen et
al. (47) reported their experience with Mohs microsurgery, which was performed
in 26 patients with lentigo maligna and 19 patients with lentigo maligna
melanoma. After a median follow-up of 58 months (214.3 patient years), there
was one recurrence, in a patient with five prior recurrences before Mohs
micrographic surgery.
Kuflik and
Gage (149) treated 30 patients with cryosurgery. Lesions ranged from 1.3 to 4.5
cm in diameter. Lesions recurred in two patients (recurrence rate of 6.6%) who
were successfully retreated with cryosurgery. Eleven patients observed for more
than 5 years showed no recurrences.
Radiation
therapy with various techniques has been frequently used in the treatment of
these patients, particularly those with larger lesions, because of minimal
morbidity and generally excellent cosmetic results (Fig. 45.16).
Figure
45.16.Lentigo maligna melanoma of face before (A) and 6 years after (B) 50 Gy
in 25 fractions delivered with 9-MeV electrons and bolus.
Radiation
Therapy Techniques
As in other
skin lesions, the portals should be carefully designed to include the entire
tumor with adequate margin (1 cm for lesions <2 cm and 2 cm for larger
tumors). Because Miescher's irradiation technique used very superficial x-rays,
with 50% depth dose being at approximately 1 mm, there is the possibility of
local recurrence if dermal extension is unrecognized. Therefore, Harwood and
Lawson (111) recommend using minimum x-ray energies of 100 keVp and preferably
140 to 175 keVp to treat these patients. Superficial x-rays (100 to 200 keVp)
with adequate filtration or electrons (6 to 9 MeV) with appropriate thickness
of bolus (about 1.5 cm) are adequate for most patients. Doses of 45 to 50 Gy in
15 to 25 fractions delivered over 3 to 5 weeks will control the disease in most
patients. We recommend delivering 3 to 3.5 Gy, three times weekly, every other
day, to a total of 50 Gy, depending on the size and thickness of the lesion.
Elective irradiation of the regional lymphatics is not necessary.
Careful
follow-up with clinical examinations and photographs of the lesion is essential
to ascertain the continuing regression of the tumor.
In patients
on whom surgical excision is performed, postoperative irradiation is
recommended if positive margins are found (111). Doses are similar to those
stated earlier.
Results of
Therapy
Kopf et al.
(146) reported six recurrences in 16 patients treated with 50 keV x-rays (500
cGy doses).
Harwood and
Lawson (111) described 13 patients with lentigo maligna treated with radiation
therapy: 11 had local tumor control, one had an edge recurrence salvaged by
irradiation, and one had residual tumor (alive and well 11 years after
treatment for the recurrence). One patient alive at 2 years refused further
treatment. Of 19 patients irradiated for LMM, 17 had tumor control with
radiation therapy alone for periods ranging from 6 months to 6 years. One
patient had a central recurrence that was salvaged by surgery (alive and well 5
years after treatment of recurrence). One patient died of intercurrent disease
<3 months after irradiation. No patient has developed lymph node or distant
metastases in either group.
Tsang et
al. (269) described results in 54 patients treated with radiation therapy or
surgery. Younger patients with smaller lesions were treated with surgical
excision (18 patients) and achieved actuarial tumor control of 94% at 3 years.
Older patients with larger lesions located in the head and neck area were
treated by radiation therapy (36 patients), with an actuarial tumor control
rate of 86% at 5 years. No patient developed metastatic melanoma. The late
cosmetic appearance was acceptable in the majority of irradiated patients, with
11% showing poor cosmesis because of progressive skin pallor, atrophy, and
telangiectasia in the treated area.
Sarcomas of the Head and Neck
Natural
History
Sarcomas
account for <1% of malignant neoplasms in the head and neck. The most
frequent histological type is malignant fibrohistocytoma (29%), while the least
common is liposarcoma (1%) (35). The histology is complex and requires
immunochemical analysis including osteosarcoma, angiosarcoma, chondrosarcoma,
hemangiosarcoma, leiomyosarcoma, liposarcoma, malignant fibrous sarcoma,
rhabdomyosarcoma, malignant schwannoma, neurofibrosarcoma, and synovial
sarcoma. Fibrosarcoma, angiosarcoma, leiomyosarcoma, and rhabdomyosarcoma are
the most common types but this varies in published reports. Table 45.15
summarizes the distribution of various histologic types in 1,127 patients.
Distribution of these sarcomas was 33% in the scalp or face, 26% in the orbit
or paranasal sinuses, 14% arising from upper aerodigestive tract including
larynx, and 27% in the neck. Synovial sarcomas are rare soft-tissue
malignancies in the head and neck region; they account for 3% to 5% of head and
neck tumors. Histologic, immunohistochemical, and characteristic chromosomal
translocation findings are necessary for diagnosis. The poor prognosis of this
sarcoma justifies radical surgery with postoperative radiation.
Table
45.15. Histologic Distribution of Head and Neck Sarcomas: Review of the
Literature
Radiation-induced
sarcoma of the head and neck is a rare long-term complication of treatment. The
rarity of this tumor is reflected in the very few series reported in the
English language medical literature (132,207). When they do occur, most appear
at least 10 years following radiation therapy. There is a possibility of a
postirradiation sarcoma whenever a suspicious lesion is seen, regardless of the
amount of time that has passed since radiation therapy was administered. The
original pathology should be re-examined to ensure that the original tumor was
diagnosed correctly. Electron microscopy can be useful in differentiating
sarcomatous-appearing epithelial lesions from true soft-tissue sarcomas.
The
incidence of radiation-induced sarcomas of the head and neck is, however,
likely to increase due to progressive aging of the population combined with
improved survival in head and neck cancer patients. This problem can be
extremely challenging and the overall outlook has been reported to be very
bleak. Patel et al. (207) reviewed 69 cases reported in the English medical literature
since 1966 and pooled this information with their experience in treatment of 10
patients. This group was compared for survival with 124 patients with a
diagnosis of head and neck sarcoma registered on the Head and Neck Sarcoma
database at the Royal Marsden Hospital. There was no site prediction for
radiation-induced sarcoma of the head and neck, but malignant fibrous
histiocytoma was the most common pathologic diagnosis. The period of latency
between initial radiation therapy and diagnosis ranged from 9 to 45 years with
a median of 17 years. Surgery was the mainstay of treatment, and follow-up
ranged from 6 months to 15 years with a median of 48 months. The actuarial
5-year diseasefree survival rate in these patients was 60%.
Clinical
Presentation and Diagnostic Work-Up
Clinical
presentation varies with the primary site of disease.
Tumors
arising from the aerodigestive tract usually present with nasal bleeding, a
palpable mass in the neck, or difficulty in swallowing or breathing. Of tumors
arising from the base of skull or the nerve sheath, cranial nerve deficit is
the most common presentation. Diagnostic work-up follows that of softtissue
sarcomas of other sites in the body. With early lesions, radiographs or CT may
show only nonspecific opacification, soft-tissue swelling, and occasionally
bone destruction. Table 45.1 outlines the suggested diagnostic work-up. MRI,
especially with gadolinium contrast, may be used as a supplement or alternative
to CT scanning (161). A CT scan of the chest is also mandatory for staging
work-up.
The
American Joint Committee on Cancer (AJCC) staging system for soft-tissue
sarcomas is based on histologic grade, the tumor size and depth, and the
presence of distant or nodal metastases. The staging system is the same as for
sarcomas of the extremities, although specific staging for head and neck
sarcomas is not standardized (49).
Prognostic
Factors
Prognostic
factors for predicting local recurrence or diseasefree survival include
anatomic site, treatment modality, tumor histology and grade, tumor size,
extension of disease, and surgical margins (69,73,286).
A report
from Royal Marsden Hospital showed anatomic location and treatment modality to
be independent prognostic factors for local recurrence; tumors of the head had
a better local recurrencefree survival than did those of the neck (73).
Patients treated with a combination of surgery and radiation therapy had a
better recurrencefree survival than did those treated with surgery or
irradiation alone. The only significant independent prognostic factor for
overall survival was the implementation of definitive surgery versus biopsy. In
the above report, the prognostic impact of tumor stage and grade did not reach
statistical significance. In contrast, Tran et al. (266) reported that 90% of
patients with low-grade tumors were free of disease versus only 16% with
high-grade lesions.
Bentz et
al. (19) reviewed 111 head and neck sarcoma patients; median duration of
follow-up was 51 months; the actuarial 5-year relapsefree disease-specific, and
overall survivals were 55%, 52%, and 44% respectively. By multivariate
analysis, size and grade significantly influenced all survivals, whereas margin
status additionally influenced relapsefree survival.
In 352
patients treated at the Mayo Clinic for primary soft-tissue sarcoma of the head
and neck, the 5-year overall survival for nonmetastasizing tumors such as
dermatofibrosarcoma, protuberans, and desmoid tumors was 100%. Of the tumors
with metastasizing potential that presented without lymph node metastasis or
distant metastasis, the 5-year overall survival rate was 62.9% but decreased to
25% when lymph node or distant metastasis was detected at presentation (87).
In 109
soft-tissue sarcomas of all sites, a French study demonstrated that quality of
the surgery was one of the most important variables for predicting local
recurrences. Tumor size, surgical margins, presence of tumor necrosis, and
adequacy of the excision correlated with metastasisfree survival (169).
In 57
patients with soft-tissue sarcomas of the head and neck treated at
Massachusetts General Hospital, angiosarcoma had a considerably poorer
prognosis than other histologies (257). In addition to tumor grade and size,
direct tumor extension to neurovascular structures, bone, contiguous organs,
and skin was associated with a higher incidence of distant metastasis. The
actuarial 5-year freedom-from-distant-metastasis rates were 70% and 100% for
tumors with or without direct extension, respectively.
General
Management
Surgery is
the preferred initial treatment modality for sarcomas (50). Unfortunately, it
is often difficult to achieve complete resection of the tumor, and a high
recurrence rate has been observed with surgery alone (82). Extracapsular
enucleation of the tumor results in 90% local recurrence because of the
presence of microscopic pseudopodia, which tend to grow through the
pseudocapsule into the surrounding tissue and the presence of skipped lesions
some distance from the main tumor mass. Pathologic analysis of the surgical bed
often discloses microscopic extension of tumor. Farhood et al. (82), in a
review of 176 cases of adult head and neck sarcomas, reported that the
pathologic margins of surgical specimens obtained by wide local excision were
positive in more than 50% of cases. This resulted in inferior overall survival
for sarcomas of the head and neck when compared with extremity sarcomas (225).
Wide local excision, with a 5-cm margin around the pseudocapsule in extremity
sarcomas, is associated with better outcome, although approximately 20% will
have local recurrence. The criteria for surgical resection are impractical for
head and neck sarcomas because of anatomic limitations (49); wide local
excision is rarely possible because the tumors extend beyond the confines of
origin and in the proximity of vital neurovascular structures. Some
retrospective studies have suggested improved local tumor control when combined
surgery and external irradiation are used. In 130 patients with soft-tissue
sarcomas of the head and neck treated with surgery alone at Royal Marsden
Hospital, the overall 5-year survival was 50%; local tumor control was only
47%, and local recurrence was the cause of death in 63% of cases. Patients
treated with combined-modality treatment (surgery and irradiation) had less
extensive surgery, yet local recurrencefree survival was longer (73).
Radiation
therapy, by external beam or brachytherapy, plays an important adjunctive role
in the management, especially for tumors where en-bloc resection with negative
margin is not possible (255,286). Chemotherapy regimens are available for
soft-tissue neoplasms primarily designed to improve local tumor control (175).
Survival is predicted on the incidence of local recurrence and risk of distant
metastasis, both of which are influenced by tumor grade.
A
systematic review of radiation therapy trials was performed by the Swedish
Council of Technology Assessment in Health Care (SBU) (255). This synthesis of
the literature on radiation therapy for soft-tissue sarcomas is based on data
from five randomized trials. Moreover, data from six prospective studies, 25
retrospective studies, and three other articles were used. In total, 39
scientific articles were included, involving 4,579 patients. The results were
compared with those of a similar overview from 1996 which included 3,344
patients. There was evidence that adjuvant radiotherapy improves local tumor
control in combination with conservative surgery with negative, marginal, or
minimal microscopic positive surgical margins. There are still insufficient
data to establish that preoperative radiotherapy is favorable compared to
postoperative radiotherapy in patients presenting primarily with large tumors.
The preoperative setting results in more wound complications. There is no
randomized study comparing external beam radiotherapy and brachytherapy. The
data suggest that external beam radiotherapy and low-dose-rate brachytherapy
result in comparable local control for high-grade tumors. Some patients with
low-grade soft-tissue sarcomas benefit from external beam radiotherapy in terms
of local control. Brachytherapy with a low dose rate for low-grade tumors seems
to be of no benefit, but data are sparse. In two small studies investigating
hyperfractionation schedules there was no indication of improvements compared
to daily fractions of 2 Gy.
Mesenchymal
chondrosarcoma of the sinonasal tract is a rare, malignant tumor of
extraskeletal origin (141). Thirteen patients with sinonasal mesenchymal
chondrosarcoma presented with nasal obstruction (n = 8), epistaxis (n = 7), or
mass effect (n = 4), or a combination of these. The maxillary sinus was the
most common site of involvement (n = 9), followed by the ethmoid sinuses (n =
7) and the nasal cavity (n = 5). All cases were managed by surgery with
adjuvant radiation therapy (n = 4) and/or chemotherapy (n = 3). The overall
mean survival was 12.1 years, although 5/6 patients who developed local
recurrences died of disease (mean survival, 6.5 years). Six patients were alive
and disease free (mean survival, 17.3 years), and two patients were lost to
follow-up (141).
A
multidisciplinary discussion before the initiation of treatment is required to
formulate the best approach for radiation delivery, surgical technique, and
mode of reconstruction.
Radiation
Therapy Techniques
The general
principles for radiation therapy of head and neck sarcomas are similar to those
of soft-tissue sarcomas. Complete coverage of the surgical bed and scar with
adequate margins (3 to 5 cm) is required (210). However, because of the
proximity of critical and radiosensitive organs (eyes, spinal cord, brainstem),
selecting optimal portal margins without seriously compromising the functioning
of these organs is an art. Techniques similar to those used in epithelial
tumors of the head and neck can be applied to sarcomas. In general, 55 to 60 Gy
is needed for postoperative adjuvant irradiation, and an additional 10- to
15-Gy boost is recommended if the surgical margins are close (≤3 mm) or
involved by tumor. Some institutions prefer preoperative irradiation of 45 to
50 Gy. Special attention should be directed to limiting the dose to critical
structures. Use of a 3D treatment technique can be considered as demonstrated
in Fig. 45.11.
Results of
Therapy
Because of
the propensity for sarcomas to invade the surrounding tissues, complete
surgical clearance may be difficult (1). In a series from UCLA, attempted
en-bloc resection left residual tumor at the surgical margins in 52/127 patients
(266). The incidence of local recurrence was high (60%) with surgery alone.
In a
retrospective report of 73 patients with sarcomas of the head and neck treated
at Princess Margaret Hospital, the 5-year cause-specific survival was 62%, with
a local recurrence rate of 41% and a distant metastasis rate of 31% (159).
Extension to adjacent structures, high-grade tumor, and tumor >10 cm were
associated with poor survival. Gross residual tumor after surgery was also
associated with a high local recurrence rate (75%) despite the addition of
radiation therapy. Patients with clear surgical margins or only microscopic
involvement fared much more favorably and had a similar local tumor control
rate (74% and 70%, respectively), provided adjuvant irradiation was given.
Because of the difficulty in obtaining wide surgical margins, 68% of the
patients died as a result of uncontrolled local disease. These data
substantiate the importance of surgical margins as well as the contribution of
adjuvant irradiation (159).
Colville et
al. (49) reported on 41 male and 19 female patients treated with head and neck
soft-tissue sarcomas, overall 5-year survival was 60%. Twenty-five patients had
surgery alone, 20 surgery and pre- or postoperative radiation therapy and 15
received nonsurgical treatment. With mean follow-up of almost 4 years the
5-year local tumor control was 56% in the surgical and 40% in the nonsurgical
group (more advanced and aggressive tumors). The 5-year survival was 70% and
40%, respectively.
Penel et
al. (211) recorded their experience with 28 adult head and neck soft-tissue
sarcomas. The median age was 45.7 years (range: 18 to 86). The male/female
ratio was 15:13. The most common subtype was rhabdomyosarcoma (seven cases).
Twenty-two patients presented with previous inadequate resection performed
elsewhere before admission. Nineteen patients had surgery (complete resection
in 13 cases). Associated treatments were neoadjuvant chemotherapy, adjuvant
chemotherapy, and postoperative radiotherapy in 4, 3, and 10 cases,
respectively. The 2-year overall survival rate was 56%.
Pandey et
al. (202) reported on 22 cases of head and neck sarcomas (neck, lower jaw,
tongue, cheek, scalp, and maxilla were the commonest sites affected). None of
the patients had palpable neck nodes or distant metastasis at presentation. All
the patients were treated with primary surgical resection, followed by adjuvant
treatment in 14 cases (63.6%). After a median follow-up of 14.5 months, two
patients died, six developed local recurrence, four developed metastatic
disease, and another patient developed a second primary sarcoma. The overall
5-year survival was 80%, while the 5-year diseasefree survival rate was 24.1%.
Barker et
al. (9) published a review of 44 patients diagnosed with nonmetastatic
soft-tissue sarcoma in a head and neck. The most common tumor histologies
included malignant fibrous histiocytoma (15 patients), angiosarcoma (nine
patients), fibrosarcoma (six patients), and leiomyosarcoma (six patients). The
median overall survival for all patients was 79 months. The actuarial 5-year
local tumor control was 55% and was highly correlated with the extent of
surgical excision: 25% for subtotal resection/debulking, 65% for wide local
excision, and 100% for radical excision. Local tumor control at 5 years was 60%
for patients treated with both surgery and radiotherapy, 54% surgery alone, and
43% for radiation alone. Adjuvant radiation therapy significantly improved the
local control rates (from 25% to 54%) for patients with close (<2 mm) or positive
surgical margins. Of 14 patients with locoregional failure in whom salvage was
attempted, nine (64%) were rendered disease free.
Rapidis et
al. (221) reported on 25 patients with head and neck sarcomas with follow-up
ranging from 8 to 144 months. Twenty-three patients were treated with surgery
as the primary modality; 14 with surgery alone. Clear margins were obtained in
all of them and local control was achieved in 12/13. The 5-year survival for
the entire group was 40%. Reported results of treatment of soft-tissue sarcomas
is summarized in Table 45.16.
Table
45.16. Treatment Results of Adult Soft-Tissue Sarcomas of the Head and Neck
Tumor
Characteristics
Several
series have shown that tumor grade and size dictate the outcome of patients
with head and neck sarcomas such as leiomyosarcoma, rhabdomyosarcoma, and
malignant fibrous sarcoma (50). Farhood et al. (82), in a review of 176 adult
head and neck sarcomas, found that only 20% of the patients with high-grade
tumors were alive 10 years after treatment, as opposed to 88% of patients with
low-grade tumors. Greager et al. (101) noted mean survival of 93 months in
patients with lowgrade tumors smaller than 5 cm versus 15 months for those with
high-grade lesions larger than 5 cm. Weber et al. (282) described a 45% 10-year
survival rate for patients with tumors smaller than 5 cm versus 10% for those
with tumors 5 cm or larger.
Many series
have reported that chondrosarcoma is not a radiosensitive tumor, and radiation
therapy has no role in it treatment. However, some reports have demonstrated
the contribution of radiation therapy in this histology. Harwood et al. (110)
reported that 6/12 patients with chondrosarcoma of the bone receiving
irradiation alone were alive with no evidence of disease at periods ranging
from 3 to 16 years. McNaney et al. (180) described a 65% survival rate at 2
years in 20 chondrosarcoma patients who received primary radiation therapy.
Tumor grade was the most important prognostic factor.
Osteogenic
sarcoma of the head and neck has a pattern of recurrence different from similar
tumors elsewhere in the body. Head and neck osteosarcomas are usually high
grade; they have a very high incidence of local recurrence but a lower risk of
distant metastases. Several studies have used adjuvant irradiation and
chemotherapy, which commonly results in improved locoregional tumor control and
survival. Chambers and Mahoney (38) reported a 73% 5-year survival rate in
patients with osteogenic sarcoma of the head and neck treated with highdose preoperative
irradiation followed by wide surgical excision. Similar observations were
reported by Tran et al. (266).
Chemotherapy
Head and
neck soft-tissue sarcomas frequently metastasize; 25% of patients in the UCLA
study had distant metastases (266). The role of adjuvant chemotherapy to
improve diseasefree survival in sarcoma of the head and neck is controversial.
The results were disappointing in a randomized trial conducted by the National
Cancer Institute (99). Also, in a review of 11 randomized trials of adjuvant
chemotherapy in nonextremity soft-tissue sarcomas, Elias and Antman (74)
observed that none showed a statistically significant benefit in survival.
Unlike with softtissue sarcomas of the extremities, in which distant metastasis
is the most common cause of death, the majority of deaths in sarcomas of the
head and neck are associated with local failure. Approximately half of the
distant metastases were detected after local recurrence occurred (159).
Chemotherapy did not appear to affect local tumor control (74).
McKenna et
al. (179) reported on 16 adult patients with highgrade soft-tissue sarcomas of
the head and neck treated with surgery, radiation therapy, and chemotherapy.
With a median follow-up of 43 months, 12 patients (75%) achieved local tumor
control, and 10 patients were disease free. In a series of 94 patients treated
at UCLA (266), local control was achieved in 52% of patients treated with
surgery alone and 90% of those receiving adjuvant irradiation and/or
chemotherapy.
For
preoperative neoadjuvant chemotherapy, which supplements radiation therapy to
downstage disease before surgery, satisfactory results are available only for
sarcomas of extremities (212,227). The Institute Gustave-Roussy reported that
two thirds of locally advanced lesions could be rendered operable after
neoadjuvant chemotherapy and/or radiation therapy (227).
With the
exception of rhabdomyosarcoma, postoperative adjuvant chemotherapy should be
given only in a clinical trial setting.
