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The prognosis of EMECL is relatively good, and considerably better than most other forms of NSCLC. The skull and dura are possible sites for metastasis from pulmonary EMC. The MIB-1 index is a predictive marker of malignant potential.
Immunohistochemistry is performed as additional test. The strong positive expression of cytokeratin 19 was showed in primary SCTC, and negative in metastatic SCTC.
There are no specific radiological tests for SCTC verification. However these tests might be useful for identification of tumor borders and in planning of surgery.
EMECL is staged in the same manner as other non-small cell lung carcinomas, based on the TNM (Tumor-Node-Metastasis) staging system.
Because of its rarity, there have been no randomized clinical trials of treatment of GCCL, and all information available derives from small retrospective institutional series or multicenter metadata.
Giant-cell lung cancers have long been considered to be exceptionally aggressive malignancies that grow very rapidly and have a very poor prognosis.
Many small series have suggested that the prognosis of lung tumors with giant cells is worse than that of most other forms of non-small-cell lung cancer (NSCLC), including squamous cell carcinoma, and spindle cell carcinoma.
The overall five-year survival rate in GCCL varies between studies but is generally considered to be very low. The (US) Armed Forces Institute of Pathology has reported a figure of 10%, and in a study examining over 150,000 lung cancer cases, a figure of 11.8% was given. However, in the latter report the 11.8% figure was based on data that included spindle cell carcinoma, a variant which is generally considered to have a less dismal prognosis than GCCL. Therefore, the likely survival of "pure" GCCL is probably lower than the stated figure.
In the large 1995 database review by Travis and colleagues, giant-cell carcinoma has the third-worst prognosis among 18 histological forms of lung cancer. (Only small-cell carcinoma and large-cell carcinoma had shorter average survival.)
Most GCCL have already grown and invaded locally and/or regionally, and/or have already metastasized distantly, and are inoperable, at the time of diagnosis.
Generally, there is a good prognosis for low-grade tumors, and a poor prognosis for high-grade tumors.
a) Surgical resection is mainstay of treatment, whenever possible. If tumor is completely removed, post-operative radiation therapy is typically not needed since acinic cell is considered a low-grade histology. Post-operative radiation therapy for acinic cell carcinoma is used if: 1) margins are positive, 2) incomplete resection, 3) tumor invades beyond gland, 4) positive lymph nodes.
b) Neutron beam radiation
c) Conventional radiation
d) Chemotherapy
It is important to exclude a tumor which is directly extending into the ear canal from the parotid salivary gland, especially when dealing with an adenoid cystic or mucoepidermoid carcinoma. This can be eliminated by clinical or imaging studies. Otherwise, the histologic differential diagnosis includes a ceruminous adenoma (a benign ceruminous gland tumor) or a neuroendocrine adenoma of the middle ear (middle ear adenoma).
Prognosis is good for acinic cell carcinoma of the parotid gland, with five-year survival rates approaching is 90%, and 20-year survival exceeding 50%. Patients with acinic cell carcinomas with high grade transformation (sometimes also called dedifferentiation) have significantly worse survival.
The prognosis of an acinic cell carcinoma originating in the lung is much more guarded than cases of this rare histotype occurring in most other organs, but is still considerably better than for other types of lung cancer.
They generally have a good prognosis. In one larger study, the 5-year and 10-year survival were over 90% and 80% respectively.
Staging is a formal procedure to determine how developed the cancer is. This determines treatment options.
The American Joint Committee on Cancer (AJCC) and the International Union Against Cancer (UICC) recommend TNM staging, using a uniform scheme for non-small cell lung carcinoma, small-cell lung carcinoma and broncho-pulmonary carcinoid tumors. With TNM staging, the cancer is classified based on the size of the tumor and spread to lymph nodes and other organs. As the tumor grows in size and the areas affected become larger, the staging of the cancer becomes more advanced as well.
There are several components of NSCLC staging which then influence physicians' treatment strategies. The lung tumor itself is typically assessed both radiographically for overall size as well as by a pathologist under the microscope to identify specific genetic markers or to see if there has been invasion into important structures within the chest (e.g., bronchus or pleural cavity). Next, the patient's nearby lymph nodes within the chest cavity known as the mediastinum will be checked for disease involvement. Finally, the patient will be evaluated for more distant sites of metastatic disease, most typically with brain imaging and or scans of the bones.
The survival rates for stages I through IV decrease significantly due to the advancement of the disease. For stage I, the five-year survival rate is 47%, stage II is 30%, stage III is 10%, and stage IV is 1%.
There are many diagnostic methods that can be used to determine the type of salivary gland tumour and if it is benign or malignant. Examples of diagnostic methods include:
Physical exam and history: An exam of the body to check general signs of health. The head, neck, mouth, and throat will be checked for signs of disease, such as lumps or anything else that seems unusual. A history of the patient's health habits and past illnesses and treatments will also be taken.
Endoscopy: A procedure to look at organs and tissues inside the body to check for abnormal areas. For salivary gland cancer, an endoscope is inserted into the mouth to look at the mouth, throat, and larynx. An endoscope is a thin, tube-like instrument with a light and a lens for viewing.
MRI
Biopsy: The removal of cells or tissues so they can be viewed under a microscope by a pathologist to check for signs of cancer.
Fine needle aspiration (FNA) biopsy: The removal of tissue or fluid using a thin needle. An FNA is the most common type of biopsy used for salivary gland cancer, and has been shown to produce accurate results when differentiating between benign and malignant tumours.
Radiographs: An OPG (orthopantomogram) can be taken to rule out mandibular involvement. A chest radiograph may also be taken to rule out any secondary tumours.
Ultrasound: Ultrasound can be used to initially assess a tumour that is located superficially in either the submandibular or parotid gland. It can distinguish an intrinsic from an extrinsic neoplasm. Ultrasonic images of malignant tumours include ill defined margins.
Staging of c-SCLC patients is usually performed in an analogous fashion to patients with "pure" small cell lung carcinoma.
For several decades, SCLC has been staged according to a dichotomous distinction of "limited disease" (LD) "vs." "extensive disease" (ED) tumor burdens. Nearly all clinical trials have been conducted on SCLC patients staged dichotomously in this fashion. LD is roughly defined as a locoregional tumor burden confined to one hemithorax that can be encompassed within a single, tolerable radiation field, and without detectable distant metastases beyond the chest or supraclavicular lymph nodes. A patient is assigned an ED stage when the tumor burden is greater than that defined under LD criteria — either far advanced locoregional disease, malignant effusions from the pleura or pericardium, or distant metastases.
However, more recent data reviewing outcomes in very large numbers of SCLC patients suggests that the TNM staging system used for NSCLC is also reliable and valid when applied to SCLC patients, and that more current versions may allow better treatment decisionmaking and prognostication in SCLC than with the old dichotomous staging protocol.
The diagnosis of salivary gland tumors utilize both tissue sampling and radiographic studies. Tissue sampling procedures include fine needle aspiration (FNA) and core needle biopsy (bigger needle comparing to FNA). Both of these procedures can be done in an outpatient setting. Diagnostic imaging techniques for salivary gland tumors include ultrasound, computer tomography (CT) and magnetic resonance imaging (MRI).
Fine needle aspiration biopsy (FNA), operated in experienced hands, can determine whether the tumor is malignant in nature with sensitivity around 90%. FNA can also distinguish primary salivary tumor from metastatic disease.
Core needle biopsy can also be done in outpatient setting. It is more invasive but is more accurate compared to FNA with diagnostic accuracy greater than 97%. Furthermore, core needle biopsy allows more accurate histological typing of the tumor.
In terms of imaging studies, ultrasound can determine and characterize superficial parotid tumors. Certain types of salivary gland tumors have certain sonographic characteristics on ultrasound. Ultrasound is also frequently used to guide FNA or core needle biopsy.
CT allows direct, bilateral visualization of the salivary gland tumor and provides information about overall dimension and tissue invasion. CT is excellent for demonstrating bony invasion. MRI provides superior soft tissue delineation such as perineural invasion when compared to CT only.
Primary treatment for this cancer, regardless of body site, is surgical removal with clean margins. This surgery can prove challenging in the head and neck region due to this tumour's tendency to spread along nerve tracts. Adjuvant or palliative radiotherapy is commonly given following surgery. For advanced major and minor salivary gland tumors that are inoperable, recurrent, or exhibit gross residual disease after surgery, fast neutron therapy is widely regarded as the most effective form of treatment.
Chemotherapy is used for metastatic disease. Chemotherapy is considered on a case by case basis, as there is limited trial data on the positive effects of chemotherapy. Clinical studies are ongoing, however.
EMCas are diagnosed by examination of tissue, e.g. a biopsy.
Its appearance is very similar to adenomyoepithelioma of the breast, which may be the same tumour at a different anatomical site.
The histologic differential diagnosis includes adenoid cystic carcinoma and pleomorphic adenoma.
Reliable comprehensive incidence statistics for c-SCLC are unavailable. In the literature, the frequency with which the c-SCLC variant is diagnosed largely depends on the size of tumor samples, tending to be higher in series where large surgical resection specimens are examined, and lower when diagnoses are based on small cytology and/or biopsy samples. Tatematsu "et al." reported 15 cases of c-SCLC (12%) in their series of 122 consecutive SCLC patients, but only 20 resection specimens were examined. In contrast, Nicholson "et al." found 28 c-SCLC (28%) in a series of 100 consecutive resected SCLC cases. It appears likely, then, that the c-SCLC variant comprises 25% to 30% of all SCLC cases.
As the incidence of SCLC has declined somewhat in the U.S. in recent decades, it is likely that c-SCLC has also decreased in incidence. Nevertheless, small cell carcinomas (including the c-SCLC variant) still comprise 15–20% of all lung cancers, with c-SCLC probably accounting for 4–6%. With 220,000 cases of newly diagnosed lung cancer in the U.S. each year, it can be estimated that between 8,800 and 13,200 of these are c-SCLC.
In a study of 408 consecutive patients with SCLC, Quoix and colleagues found that presentation as a solitary pulmonary nodule (SPN) is particularly indicative of a c-SCLC — about 2/3 of their SPN's were pathologically confirmed to be c-SCLC's containing a large cell carcinoma component.
This type of carcinoma is commonly managed by local resection, cryotherapy, topical chemotherapy, and radiotherapy. Multimodal therapy has been shown to improve both visual prognosis and survival.
Mohs micrographic surgery has become the treatment of choice for this form of cancer. When used as the primary treatment modality for sebaceous carcinoma of the eyelid, Mohs surgery is associated with significantly lower local and distant recurrence rates.
Hürthle cell adenomas are most likely diagnosed much more frequently than Hürthle cell carcinomas. The female to male ratio for Hurthle cell adenomas is 8:1, while the ratio is 2:1 for the malignant version. Hürthle cell cancer tends to occur in older patients. The median age at diagnosis for Hürthle cell carcinomas is approximately 61 years old. Typically a painless thyroid mass is found in patients with this type of cancer. As expected, patients with carcinoma usually present larger tumors than patients with adenoma. Rarely, the cancer can spread to the lymph nodes. On few occasions, patients with Hürthle cell carcinoma have distant metastases in the lungs or surrounding bones. Hürthle cell neoplasms are somewhat difficult to differentiate between being benign or malignant. Since the size and growth pattern of the tumor cannot be used to determine malignancy, although larger tumors have higher incidence of malignancy, Hürthle cell adenomas and carcinomas have to be separated by the presence, in the case of carcinomas, or absence, in the case of adenomas, of both capsular invasion and vascular invasion. Tumors displaying only capsular invasion tend to behave less aggressively than those with vascular invasion. Hürthle cell carcinomas are characterized as either minimally invasive or widely invasive tumors. While the minimally invasive or encapsulated carcinoma is fully surrounded by a fibrous capsule, the widely invasive carcinoma shows extensive area of both capsular and vascular invasion with the leftover capsule typically difficult to identify. Classification is important since widely invasive tumors can have outcomes with a 55% mortality rate.
Benign myoepithelioma are treated with simple excision. They are less prone to recurrence than pleomorphic adenoma.
MASC is currently treated as a low-grade (i.e. Grade 1) carcinoma with an overall favorable prognosis. These cases are treated by complete surgical excision. However, the tumor does have the potential to recur locally and/or spread beyond surgically dissectible margins as well as metastasize to regional lymph nodes and distant tissues, particularly in tumors with histological features indicating a high cell growth rate potential. One study found lymph node metastasis in 5 of 34 MASC patients at initial surgery for the disease; these cases, when evidencing no further spread of disease, may be treated with radiation therapy. The treatment of cases with disease spreading beyond regional lymph nodes has been variable, ranging from simple excision to radical resections accompanied by adjuvant radiotherapy and/or chemotherapy, depending on the location of disease. Mean disease-free survival for MASC patients has been reported to be 92 months in one study.
The tyrosine kinase activity of NTRK3 as well as the ETV6-NTRK3 protein is inhibited by certain tyrosine kinase inhibitory drugs such as Entrectinib and LOXO-101; this offers a potential medical intervention method using these drugs to treat aggressive MASC disease. Indeed, one patient with extensive head and neck MASC disease obtained an 89% fall in tumor size when treated with entrectinib. This suppression lasted only 7 months due to the tumor's acquirement of a mutation in the "ETV6-NTRK3" gene. The newly mutated gene encoded an entrectinib-reisistant "ETV6-NTRK3" protein. Treatment of aggressive forms of MASC with NTRK3-inhibiting tyrosine kinase inhibiting drugs, perhaps with switching to another type of tyrosine kinase inhibitor drug if the tumor acquires resistance to the initial drug, is under study.STARTRK-2
Most of these tumors are treated with surgical removal. It is non recurrent.
Immunohistochemistry will help to show the biphasic appearance of the tumor, highlighting the basal or the luminal cells:
- Luminal cells: positive with CK7 and CD117
- Basal cells: positive with p63, S100 protein and CK5/6