 |
[Home] | [Search] | [Medical Q&A Forums] | [Patient Network] |
This information has been brought to you by
Med Help International,
licenced by the National Cancer Institute as a distributor of CancerNet.
CancerMail from the National Cancer Institute
******************************************************************************
* This information is intended mainly for use by doctors and other health *
* care professionals. If you have questions about this topic, you can ask *
* your doctor, or call the Cancer Information Service at 1-800-4-CANCER *
* (1-800-422-6237). *
******************************************************************************
Information from PDQ -- for Health Professionals
Unusual cancers of childhood
208/10612
** DISEASE DESCRIPTION **
-- GENERAL INFORMATION --
This treatment information summary for children with unusual cancers is an
overview of prognosis, diagnosis, classification, and treatment. The National
Cancer Institute created the PDQ database to increase the availability of new
treatment information and its use in treating patients. Information and
references from the most recently published literature are included after
review by pediatric oncology specialists.
Cancer in children and adolescents is rare. Children and adolescents with
cancer should be referred to medical centers that have a multidisciplinary team
of cancer specialists with experience treating the cancers that occur during
childhood and adolescence. This multidisciplinary team incorporates the skills
of the primary care physician, pediatric surgical subspecialists, radiation
oncologists, pediatric medical oncologists/hematologists, rehabilitation
specialists, pediatric nurse specialists, social workers, and others in order
to ensure that children receive treatment, supportive care, and rehabilitation
that will achieve optimal survival and quality of life. Guidelines for
pediatric cancer centers and their role in the treatment of pediatric patients
with cancer have been outlined by the American Academy of Pediatrics.[1] At
these pediatric cancer centers, there are clinical trials available for most of
the types of cancer that occur in children and adolescents, and the opportunity
to participate in these trials is offered to most patients/families. Clinical
trials for children and adolescents diagnosed with cancer are generally
designed to compare potentially better therapy with therapy that is currently
accepted as standard. Much of the progress made in identifying curative
therapies for childhood cancers has been achieved through clinical trials.
Information about ongoing clinical trials is available from the NCI
(http://cancer.gov/clinical_trials/).
The tumors discussed in this summary are diverse; the discussion is arranged in
descending anatomic order, from infrequent tumors of the head and neck to rare
tumors of the urogenital tract and skin. All of these cancers are rare enough
that most pediatric hospitals might see fewer than two in a year. Most of
these tumors are more frequent in adults with cancer; thus, much of the
information about these tumors may also be sought through sources relevant to
adults with cancer.
-- HEAD AND NECK CANCERS --
Head and neck cancers include nasopharyngeal carcinoma, thyroid tumors, mouth
cancer, salivary gland cancer, and laryngeal carcinoma. The prognosis,
diagnosis, classification, and treatment of these head and neck cancers are
discussed below.
-- Nasopharyngeal Carcinoma --
Nasopharyngeal cancer arises in the lining of the nasal cavity and pharynx.[2]
This tumor accounts for about one-third of all cancers of the upper airways.
The incidence of this tumor is approximately one in 100,000 persons under the
age of 20 in the United States.[3] There is a higher frequency of this tumor
in North Africa and Southeast Asia.
Nasopharyngeal carcinoma occurs in association with Epstein-Barr virus (EBV),
the virus associated with infectious mononucleosis. The virus can be detected
in biopsy specimens of these cancers, and tumor cells can have EBV antigens on
their cell surface. Three histologic subtypes are recognized by the World
Health Organization. Type 1 is squamous cell carcinoma, type 2 is
nonkeratinizing carcinoma, and type 3 is undifferentiated carcinoma.
This cancer most frequently spreads to lymph nodes in the neck, which may alert
the patient, parent, or physician to the presence of this tumor. The tumor may
also spread to the nose, mouth, and pharynx, causing snoring, epistaxis,
obstruction of the eustachian tubes, or hearing loss; it may also invade the
base of the skull, causing cranial nerve palsy or difficulty with movements of
the jaw (trismus). Distant metastatic sites may include the bones, the lungs,
and the liver. The location of the primary tumor can be made by direct
inspection of the nasopharynx. A diagnosis can be made from a biopsy of the
primary tumor or of enlarged lymph nodes of the neck. Nasopharyngeal
carcinomas must be distinguished from all other cancers that can present with
enlarged lymph nodes and from other types of cancer in the head and neck area.
Thus, diseases such as thyroid cancer, rhabdomyosarcoma, non-Hodgkin's
lymphoma, Hodgkin's lymphoma, and Burkitt's lymphoma must be considered, as
should benign conditions such as nasal angiofibroma (which presents with
epistaxis) and infections draining into the lymph nodes of the neck.
Diagnostic tests should determine the extent of the primary tumor and whether
there are metastases. Visualization of the nasopharynx by an ear-nose-throat
specialist using a mirror, examination by a neurologist, and magnetic resonance
imaging (MRI) of the head and neck can be used to determine the extent of the
primary tumor. Evaluation of the chest and abdomen by computed tomography (CT)
and bone scan should also be performed to determine whether there is metastatic
disease. The levels of EBV and antibody to EBV should also be measured.[2,4]
Tumor staging is done by the tumor-node-metastasis (TNM) classification system
of the American Joint Committee on Cancer. Various reports have indicated an
overall survival rate of at least 75% for patients with early stage disease;
there is a lower survival rate for patients with higher stage disease.[5,6] No
factors other than extent of tumor have correlated with prognosis.
Treatment combines the use of surgery, radiation therapy, and chemotherapy.[7]
Nasopharyngeal carcinoma generally has spread to the bones of the skull and to
lymph nodes in the neck at the time of diagnosis; thus, the principal role of
surgery is to obtain adequate diagnostic material from a biopsy of the involved
lymph node or the primary site. Combined modality therapy with radiation and
chemotherapy appears to be the most effective treatment for this tumor.[8,9]
Chemotherapy approaches include neoadjuvant and/or adjuvant therapy with
cisplatin, 5-fluorouracil, and methotrexate. Radiation dose to the tumor
should be greater than 60 Gy. An overall survival rate of 78% has been
reported with this approach.[10,11] Refer to the PDQ summary on Nasopharyngeal
Cancer Treatment for more information.
-- Thyroid Tumors --
Tumors of the thyroid are classified as adenomas or carcinomas.[12] Adenomas
are benign growths that may cause enlargement of all or part of the gland,
which extends to both sides of the neck and can be quite large. Some of these
tumors may secrete hormones. Transformation to a malignant carcinoma may occur
in some cells, which then may grow and spread to lymph nodes in the neck or to
the lungs.
Most thyroid carcinomas occur in girls. Although rare, these cancers represent
about 1.5% of all tumors seen in the pediatric age group. There is an
excessive frequency of thyroid adenoma and carcinoma in patients who previously
received irradiation to the neck.[13,14] Thyroid cancer may be associated with
the development of other types of malignant tumors, such as the multiple
endocrine neoplasia (MEN) syndromes. Thyroid carcinomas are differentiated
tumors, meaning that they tend to grow slowly and are not highly malignant.
Thyroid radionuclide scans do not demonstrate the uptake of radioisotope into
the area of the suspected neoplasm.
Various histologies account for the general diagnostic category of carcinoma of
the thyroid.[15] Papillary carcinoma represents 60% to 75% of these
tumors,[16] follicular carcinoma 10% to 20%, medullary carcinoma 5% to 10%, and
anaplastic carcinoma less than 1%. Follicular carcinomas may be sporadic or
familial. Follicular carcinoma and papillary carcinoma generally have a benign
course, with an approximately 80% 10-year survival rate. Fifty percent of
medullary thyroid carcinomas, which may be familial, have hematogenous
metastases at diagnosis.[17] Follicular carcinoma may also have a high
incidence of metastases, whereas papillary carcinomas often have multicentric
origin. Patients with medullary carcinoma of the thyroid have a guarded
prognosis, unless they have very small tumors ("microcarcinoma," defined as
less than 1.0 cm in diameter), which carry a good prognosis.[18]
Surgery is the treatment required for all thyroid neoplasms. Total
thyroidectomy is recommended for medullary cancer, and the resected parathyroid
glands generally are autotransplanted to other sites such as the forearm.[19]
A more conservative approach is recommended for papillary carcinoma, with lymph
node dissection leading to near total thyroidectomy. Over the 4 to 6 weeks
following surgery, patients may develop hypothyroidism. A radioactive iodine
scan is performed to search for residual neoplasm in the functioning thyroid
tissue. After the thyroid scan, radioactive iodine (I-131) treatment is given
at a dose of 100 to 150 mCu, and the patient is kept in a safe area overnight
or until the kidney clears virtually all of the radioactive component. In the
postoperative period, hormone replacement therapy must be given to compensate
for the lost thyroid hormone.[20] I-131 is usually successful in suppressing
thyroid function, after which the patient is treated with synthetic thyroid
hormones for life. Periodic evaluations are required to determine whether
there is metastatic disease involving the lungs. Lifelong follow-up is
necessary.[21] Thyroglobulin levels, T4, and TSH levels should be evaluated
periodically to determine whether replacement hormone is appropriately dosed.
Patients with thyroid cancer generally have an excellent survival with
relatively few side effects.[21] Recurrence is common, however, and is seen
more often in children younger than 10 years old.[22] Even patients with tumor
that has spread to the lungs may expect to have no decrease in life span after
appropriate treatment. Refer to the PDQ summary on adult Thyroid Cancer
Treatment for more information.
-- Oral Cancers --
Cancer of the mouth in children or in adolescents is extremely rare.[3] This
cancer primarily occurs in adults older than 50 years who have used tobacco for
many years; however, it can occur in survivors of other childhood tumors who
have had radiation therapy to this area. Evidence suggests that oral cancer at
younger ages primarily results from the use of smokeless tobacco products among
preadolescent boys.[19] Changes in the texture, color, and shape of the
mucosal lining of the mouth have been seen, together with degenerative changes
of the gingiva, in more than half of all teenagers who use smokeless
tobacco.[23] Precancerous lesions are common among children. Squamous cell
carcinoma, the most frequent type of cancer in these sites, must be
distinguished from benign tumors of the pharynx and neck, e.g., dermoid cysts,
lipomas, myofibromas, cystic hygroma, and teratomas. Other tumors in this area
may include ameloblastoma or adamantinoma, a rare tumor that may arise in the
mandible or the maxilla, as well as in the long bones.[24] The treatment of
ameloblastoma is surgical resection, if possible. Ameloblastoma may be benign
or malignant; pulmonary metastases may be discovered many years after treatment
for this tumor. Refer to the PDQ summary on adult Oropharyngeal Cancer
Treatment for more information.
-- Salivary Gland Cancers --
Many salivary gland cancers arise in the parotid gland.[25,26] About 15% of
these tumors may arise in the submandibular glands or in the minor salivary
glands under the tongue and jaw. These tumors are most frequently benign, but
on very rare occasions, may be malignant. The malignant lesions include
adenocarcinoma, undifferentiated carcinoma, acinic cell carcinomas, and
mucoepidermoid carcinoma. These tumors may occur after radiation therapy is
given for treatment of primary leukemia or solid tumors. Radical surgical
removal is the treatment of choice, whenever possible, with additional use of
radiation therapy and chemotherapy for high-grade tumors or tumors that have
spread from their site of origin.[27,28] Prognosis for patients with these
tumors is generally good.[29] Refer to the PDQ summary on adult Salivary Gland
Cancer Treatment for more information.
-- Laryngeal Carcinoma --
Benign and especially malignant tumors of the larynx are rare. Malignant
tumors may be associated with benign tumors such as polyps and
papillomas.[30,31] These tumors may cause hoarseness, difficulty swallowing,
and enlargement of the lymph nodes of the neck. Rhabdomyosarcoma is the most
common malignant tumor of the larynx in the pediatric age group. Squamous cell
carcinoma of the larynx should be managed in the same manner as in adults with
carcinoma at this site, with surgery and radiation. Laser surgery may be the
first type of treatment utilized for these lesions.
Papillomatosis of the larynx is a benign overgrowth of tissues lining the
larynx, associated with the human papillomavirus.[32] This condition is not
cancerous and may be treated with interferon.[33] These tumors can cause
hoarseness because of their association with wart-like nodules on the vocal
cords and may extend into the lung, producing significant morbidity. Malignant
degeneration may occur, with development of cancer in the larynx. Refer to the
PDQ summary on adult Laryngeal Cancer Treatment for more information.
-- THORACIC CANCERS --
Thoracic cancers include breast cancer, bronchial adenomas, bronchial carcinoid
tumors, pleuropulmonary blastoma, esophageal tumors, thymomas, tumors of the
heart, and mesothelioma. The prognosis, diagnosis, classification, and
treatment of these thoracic cancers are discussed below.
-- Breast Cancer --
Most tumors that involve the breast during childhood are benign, yet carcinomas
have been reported in both males and females younger than 21 years.[34-37]
There is an increased lifetime risk of breast cancer in female survivors of
Hodgkin's disease who were treated with radiation to the chest area.[37]
Carcinomas are more frequent than sarcomas. Mammograms should start at age 25
for any patient who has had radiation therapy to the chest. Treatment options
include radiation, chemotherapy, and surgery for children and adolescents with
breast cancer. Breast tumors may also occur as metastatic deposits from
leukemia, rhabdomyosarcoma, or other sarcomas. Refer to the PDQ summary on
adult Breast Cancer Treatment for more information.
-- Bronchial Adenomas/Carcinoids --
Bronchial adenomas, which are slow-growing neoplasms, are also called carcinoid
tumors.[38-40] Primary treatment of these tumors is surgical resection. For
bronchial carcinoid tumors, nuclear scans may demonstrate uptake of
radioactivity by the tumor or lymph nodes, suggesting metastatic spread.
Neither chemotherapy nor radiation therapy is indicated for bronchial
carcinoid, unless evidence of metastasis is documented.
-- Pleuropulmonary Blastoma --
Pleuropulmonary blastoma is a rare and highly aggressive pulmonary malignancy
in children. The tumor usually is located in lung periphery, but it may be
extrapulmonary with involvement of the mediastinum, diaphragm, and/or
pleura.[41] The tumors may recur or metastasize, in spite of primary
resection.[42] Responses to chemotherapy have been reported with agents
similar to those used for the treatment of rhabdomyosarcoma.[43]
Chemotherapeutic agents may include vincristine, cyclophosphamide,
dactinomycin, and doxorubicin. Radiation, either external beam or p32, may be
used when the tumor cannot be surgically removed. A family history of cancer
in close relatives has been noted for many young patients affected by this
tumor.[44]
-- Esophageal Tumors --
Esophageal cancer is rare in the pediatric age group, although it is relatively
common in older adults.[45] Symptoms are related to difficulty in swallowing
and associated weight loss. Most of these tumors are squamous cell carcinomas,
although sarcomas can also arise in the esophagus. The most common benign
tumor is leiomyoma. Diagnosis is made by histologic examination of biopsy
tissue.
Treatment options for esophageal carcinoma include either external beam,
intracavitary radiation therapy, or chemotherapy with the platinum derivatives,
paclitaxel, and etoposide, agents commonly used to treat carcinomas. Prognosis
generally is poor for this cancer, which rarely can be completely resected.
Refer to the PDQ summary on adult Esophageal Cancer Treatment for more
information.
-- Thymomas --
A cancer of the thymus is not considered a thymoma unless there are neoplastic
changes of the epithelial cells that cover the organ.[46] Other tumors that
involve the thymus gland include lymphoma, germ cell tumors, carcinomas,
carcinoid, and thymoma. Hodgkin's disease and non-Hodgkin's lymphoma may also
involve the thymus and must be differentiated from true thymomas.
Thymomas are rare in adults and children.[47] Various diseases and syndromes
are associated with thymoma, including myasthenia gravis, polymyositis,
systemic lupus erythematosus, rheumatoid arthritis, thyroiditis, and pure red
cell aplasia.[48] Endocrine (hormonal) disorders including hyperthyroidism,
Addison's disease, and panhypopituitarism can also be associated with a
diagnosis of thymoma.[49]
Thymomas are usually located in the front part of the chest, and are usually
discovered during a routine chest x-ray. Symptoms can include cough,
difficulty with swallowing, tightness of the chest, chest pain, and shortness
of breath although nonspecific symptoms may occur. These tumors generally are
slow-growing, but are potentially invasive, with metastases to distant organs
or lymph nodes. Staging is related to invasiveness. Surgery is performed with
the goal of a complete resection.
Radiation therapy is necessary for patients with invasive thymoma, whether or
not there has been a complete resection.[49] Chemotherapy is usually reserved
for patients with advanced stage disease who have not responded to radiation
therapy or corticosteroids. Agents that have been effective include
doxorubicin, cisplatin, and paclitaxel.[49-51] The prognosis for patients with
invasive thymoma usually is poor, although significantly higher rates of
survival have been reported for patients with tumors that are not locally
invasive. Thymic carcinoma, which microscopically resembles undifferentiated
nasopharyngeal carcinoma, is associated with Epstein-Barr virus infection, as
is nasopharyngeal carcinoma. This tumor is responsive to chemotherapy and is
potentially curable. Refer to the PDQ summary on adult Malignant Thymoma
Treatment for more information.
-- Tumors of the Heart --
The most common tumors of the heart are benign and include myxomas and
neurofibromas, i.e., tumors of the nerves that innervate the muscles.[52]
Other tumors of the heart can include metastatic spread of rhabdomyosarcoma,
melanoma, leukemia, and carcinoma of other sites. Primary tumors of the heart
may include benign and malignant teratoma, rhabdomyosarcoma, hemangioma, and
chondrosarcoma. Symptoms include abnormalities of heart rhythm, enlargement of
the heart, fluid in the pericardial sac, and congestive heart failure.
Successful treatment requires surgery, which may include transplantation, and
chemotherapy appropriate for the type of cancer that is present.[53,54]
-- Mesothelioma --
This tumor can involve the membranous coverings of the lung, the heart, or the
abdominal organs.[55] These tumors can spread over the surface of organs,
without invading far into the underlying tissue, and may spread to regional or
distant lymph nodes. Mesothelioma may develop after successful treatment of an
earlier cancer, especially after treatment with radiation.[56,57] In adults,
these tumors have been associated with exposure to asbestos, which was used as
building insulation.[58] The amount of exposure required to develop cancer is
unknown, and there is no information about the risk for children exposed to
asbestos.
Benign and malignant mesotheliomas cannot be differentiated using histologic
criteria. A poor prognosis is associated with lesions that are diffuse and
invasive or for those that recur. In general, the course of the disease is
slow, and long-term survival is common. Treatment with various
chemotherapeutic agents used for carcinomas or sarcomas may result in partial
responses. Pain is an infrequent symptom; however, radiation therapy may be
used for palliation of pain.
Papillary serous carcinoma of the peritoneum is sometimes mistaken for
mesothelioma.[59] This tumor generally involves all surfaces lining the
abdominal organs, including the surfaces of the ovary. Treatment includes
surgical resection whenever possible and use of chemotherapy with agents such
as cisplatin, carboplatin, and paclitaxel. Refer to the PDQ summary on adult
Malignant Mesothelioma Treatment for more information.
-- ABDOMINAL CANCERS --
Abdominal cancers include adrenocortical tumors, renal cell carcinoma,
carcinoma of the stomach, cancer of the pancreas, colorectal carcinoma,
carcinoid tumors, and multiple endocrine neoplasia syndrome. The prognosis,
diagnosis, classification, and treatment of these abdominal cancers are
discussed below.
-- Carcinoma of the Adrenal Cortex --
Adrenocortical tumors are classified as carcinomas and adenomas.[60]
Adrenocortical tumors may be hormonally active or inactive. Adenomas are
generally benign, whereas adrenocortical carcinomas frequently secrete hormones
and may cause the patient to develop masculine traits, irrespective of the
patient's gender. Pediatric patients with adrenocortical carcinoma often have
Li-Fraumeni syndrome, which is an inherited condition that predisposes family
members to multiple cancers, including breast cancer, rhabdomyosarcoma, and
osteosarcoma.[61] Children with Beckwith-Wiedemann Syndrome [62] or
hemihypertrophy [63] are at increased risk of developing carcinoma of the
adrenal cortex (as well as Wilms' tumor, hepatoblastoma, and other rare
cancers) in the first several years of life.
These tumors spread locally to the lymph nodes and can also involve the
kidneys, lungs, and bones. Surgical removal should be attempted but may not
always be possible if the tumor has spread widely. Additional treatment may
include the use of an artificial hormone that blocks the masculinizing effects
of the tumor [64] or chemotherapy using cisplatin, 5-fluorouracil, and
etoposide.[65] The prognosis for patients who have small, completely resected
tumors generally is excellent, but prognosis can be poor for patients who have
large primary tumors or metastatic disease at diagnosis.[66] Refer to the PDQ
summary on adult Adrenocortical Carcinoma Treatment for more information.
-- Renal Cell Carcinoma --
Renal cell carcinoma is the most common primary malignancy of the kidney in
adults; however, it occurs rarely in children.[67,68] The annual incidence
rate is approximately 4 per 1 million children, compared to an incidence of
Wilms' tumor of the kidney that is at least 29-fold higher. Renal cell
carcinoma may be associated with von Hippel-Lindau disease, a hereditary
condition in which blood vessels within the retina and cerebellum grow
excessively.[69] The gene for von Hippel-Lindau is on chromosome 3p14 and is a
tumor-suppressor gene whose function is lost in patients with the syndrome.
Renal cell carcinoma has also been associated with tuberous sclerosis, a
hereditary disease characterized by benign fatty cysts in the kidney.[70-72]
Familial renal cell carcinoma has been associated with an inherited chromosome
translocation involving chromosome 3.[71] A high incidence of chromosome 3
abnormalities has also been demonstrated in nonfamilial renal tumors. There is
a subset of tumors previously considered to be renal cell carcinoma in young
people that appears to be genetically related to alveolar soft part
sarcoma.[73]
Renal cell carcinoma usually presents as an abdominal mass, and there may be
discomfort, pain, and/or blood in the urine.[70] The tumor can metastasize to
the lungs, bones, liver, and lymph nodes and often has spread before the
diagnosis is made. This tumor should be considered whenever a patient presents
with a kidney mass and is older than 5 years of age.
The primary treatment includes total surgical removal of the kidney and
associated lymph nodes. Consideration should also be given to treatment with
irradiation, chemotherapy, or both. Treatment of metastatic disease is
presently unsatisfactory but usually includes the use of immune system
modulators such as interferon-alfa and interleukin-2.[74] Rare spontaneous
regression of pulmonary metastasis may occur with resection of the primary
tumor. Refer to the PDQ summary on adult Renal Cell Cancer Treatment for more
information.
-- Carcinoma of the Stomach --
The frequency and death rate from stomach cancer has declined worldwide over
the past 50 years with the introduction of food preservation practices such as
refrigeration.[75] The tumor must be distinguished from other conditions such
as non-Hodgkin's lymphoma, malignant carcinoid, leiomyosarcoma, and various
benign conditions or tumors of the stomach. Symptoms include vague upper
abdominal pain, which can be associated with poor appetite, and weight loss.
Many individuals become anemic but otherwise show no symptoms before the
development of metastatic spread. Other symptoms may include nausea, vomiting,
change in bowel habits, poor appetite, weakness, and Helicobacter pylori
infection.[76] Fiberoptic endoscopy can be used to visualize the tumor or to
take a biopsy sample to ensure the correctness of diagnosis. Confirmation can
also involve an x-ray examination of the upper gastrointestinal tract.
Treatment should include surgical excision with wide margins. For individuals
who cannot have a complete surgical resection, radiation therapy may be used
along with chemotherapeutic agents such as 5-fluorouracil and irinotecan.[77]
Other agents that may be of value are the nitrosoureas, with or without
cisplatin, etoposide, doxorubicin, or mitomycin C.
Prognosis depends on the extent of the disease at the time of diagnosis and the
success of treatment that is appropriate for the clinical situation.[78]
Because of the rarity of stomach cancer in the pediatric age group, little
information regarding the treatment outcomes of children exists. Refer to the
PDQ summary on adult Gastric Cancer Treatment for more information.
-- Cancer of the Pancreas --
Pancreatic tumors are rare in children and adolescents.[3] Tumors included in
the general category can arise at any site within the pancreas. Cancers of the
pancreas may be classified as adenocarcinoma, squamous cell carcinoma, acinic
cell carcinoma, liposarcoma, lymphoma, papillary-cystic carcinoma,
pancreaticoblastoma, malignant insulinoma, glucagonoma, and gastrinoma.[79]
Most pancreatic tumors do not secrete hormones, although some tumors secrete
insulin, which can lead to symptoms of weakness, fatigue, hypoglycemia, and
coma.[79] If tumor interferes with the normal function of the islet cells,
patients may have watery diarrhea or abnormalities of salt balance. Both
carcinoma of the pancreas and pancreaticoblastoma can produce active hormones
and can be associated with abdominal mass, wasting, and pain.[80-82] At times,
there is obstruction of the head of the pancreas, which is associated with
jaundice and gastrointestinal bleeding. Elevation of alpha-fetoprotein (AFP)
has been seen in pancreatoblastoma.[83]
The diagnosis is usually established by biopsy, using laparotomy or a minimally
invasive surgery (laparoscopy). A diagnosis can only be achieved after ruling
out various benign and cancerous lesions. Treatment includes various surgical
procedures to remove the pancreas and duodenum or removal of part of the
pancreas. For pediatric patients, the effectiveness of radiation therapy is
not known. Chemotherapy may be useful for treatment of localized or metastatic
pancreatic carcinoma. The combination of cisplatin and doxorubicin has
produced responses in pancreatoblastoma prior to tumor resection.[83] Other
agents that may be of value include 5-fluorouracil, streptozotocin, mitomycin
C, carboplatin, gemcitabine, and irinotecan. Response rates and survival rates
generally are not good.[81-83] Refer to the PDQ summary on adult Pancreatic
Cancer Treatment for more information.
-- Colorectal Carcinoma --
Carcinoma of the large bowel is rare in the pediatric age group, as it is seen
in only 1 person per 1 million younger than 20 years in the United States
annually.[84] These tumors can occur anywhere in the colon or rectum and are
often associated with a family cancer syndrome.[85] There is an increasing
risk of colorectal carcinoma in members of families with a family history of
intestinal polyposis, which can lead to the development of multiple adenomatous
polyps.[86] Juvenile polyps are not associated with an increased incidence or
risk of cancer.
Familial polyposis is inherited as a dominant trait, which confers a high
degree of risk. Early diagnosis and surgical removal of the colon eliminate
the risk of developing carcinomas of the large bowel.[87] Some colorectal
carcinomas in young people, however, may be associated with a mutation of the
adenomatous polyposis coli (APC) gene, which also is associated with an
increased risk of brain tumors and hepatoblastoma.[88] The familial APC
syndrome is caused by mutation of a gene on chromosome 5q, which normally
suppresses proliferation of cells lining the intestine and later development of
polyps.[89] Another tumor suppressor gene on chromosome 18 is associated with
progression of polyps to malignant form. Multiple colon carcinomas have also
been associated with progression of polyps to a malignant form. Multiple colon
carcinomas have been associated with neurofibromatosis type I (NF-1) and
several other rarer syndromes.[90]
The histologic types of colorectal cancer include adenocarcinoma, mucinous or
colloid adenocarcinomas, signet-ring adenocarcinoma, and scirrhous tumors.
Most tumors in the pediatric age group are mucin-producing carcinomas,[91]
whereas only about 15% of adult lesions are of this histology. The tumors of
younger patients with this histologic variant may be less responsive to
chemotherapy. These tumors arise from the surface of the bowel, usually at the
site of an adenomatous polyp. The tumor may extend into the muscle layer
surrounding the bowel, or the tumor may perforate the bowel entirely and seed
through the spaces around the bowel, including intra-abdominal fat, lymph
nodes, liver, ovaries, and the surface of other loops of bowel. A high
incidence of metastasis involving the pelvis, ovaries, or both may be present
in girls.[92]
Colorectal carcinoma usually presents with symptoms related to the site of the
tumor. Changes in bowel habits are associated with tumors of the rectum or
lower colon. Tumors of the right colon may cause more subtle symptoms, but are
often associated with an abdominal mass, weight loss, decreased appetite, and
blood in the stool. Any tumor that causes complete obstruction of the large
bowel can cause bowel perforation and spread of the tumor cells within the
abdominal cavity.
Because of its rarity, colorectal carcinoma is rarely diagnosed in a pediatric
patient; however, vague gastrointestinal symptoms should alert the physician to
investigate this possibility. Diagnostic studies that may be of value include
examination of the stool for blood, studies of liver and kidney function,
measurement of carcinoembryonic antigen, and various medical imaging studies,
including direct examination using colonoscopy to detect polyps in the large
bowel. Other conventional radiographic studies include barium enema followed
by CT of the chest and bone scans.[91,92]
Most patients present with evidence of metastatic disease, either as gross
tumor or as microscopic deposits in lymph nodes, on the surface of the bowel,
or on intra-abdominal organs. Complete surgical excision should be the primary
aim of the surgeon, but in most instances this is impossible; removal of large
portions of tumor provides little benefit for the individuals with extensive
metastatic disease. Most patients with microscopic metastatic disease
generally develop gross metastatic disease, and few individuals with metastatic
disease at diagnosis become long-term survivors.
Current therapy includes the use of radiation for rectal and lower colon
tumors, in conjunction with chemotherapy using 5-fluorouracil with
leucovorin.[93] Other agents that may be of value include irinotecan and
oxaliplatin. No significant benefit has been determined for interferon-alfa
given in conjunction with 5-fluorouracil/leucovorin.[94] Refer to the PDQ
summaries on adult Colon and Rectal Cancer Treatment for more information.
-- Carcinoid Tumors --
These tumors, like bronchial adenomas, may be benign or malignant and can
involve the lining of the lung or the large or small bowel.[95-97] Most lung
lesions are benign, however, some metastasize.[98] Most carcinoid tumors of
the appendix are small, localized tumors and simple appendectomy is the therapy
of choice.[99] For larger (>2 cm) tumors or tumors that have spread to local
nodes, cecectomy or rarely, right hemicolectomy, is the usual treatment. It
has become accepted practice to remove the entire right colon in patients with
large carcinoid tumors of the appendix (greater than 2 cm in diameter) or with
tumors that have spread to the nodes. Treatment of metastatic carcinoid tumors
of the large bowel or stomach becomes more complicated and requires treatment
similar to that given for colorectal carcinoma. The carcinoid syndrome of
excessive excretion of somatostatin is characterized by flushing, labile blood
pressure, and metastatic spread of the tumor to the liver.[98] Symptoms may be
lessened by giving somatostatin analogues, which are available in short- and
long-acting forms.
-- GENITAL/URINARY TUMORS --
Genital/urinary tumors include carcinoma of the bladder and ovarian cancer.
The prognosis, diagnosis, classification, and treatment of these
genital/urinary tumors are discussed below.
-- Carcinoma of the Bladder --
Carcinoma of the bladder is extremely rare in children. The most common
carcinoma to involve the bladder is transitional cell carcinoma, which
generally presents with hematuria.[100] The diagnosis and treatment of this
tumor are the same for children, adolescents, and adults. Adolescents who
develop this tumor are often prone to the development of other cancers,
including other bladder cancers. Bladder cancer in adolescents may develop as
a consequence of alkylating-agent chemotherapy given for other childhood tumors
or leukemia.[101,102] The association between cyclophosphamide and bladder
cancer is the only established relationship between a specific anticancer drug
and a solid tumor.[101] One of the most important risk factors for bladder
cancer in adults is cigarette smoking, which may be associated with up to 50%
of these cancers in men and 33% in women.[102] Refer to the PDQ summary on
adult Bladder Cancer Treatment for more information.
-- Ovarian Cancer --
Most cancers that affect the ovaries are of germ cell origin, which are more
common in children than adults, in whom adenocarcinomas are more frequently
encountered. Ovarian carcinomas of nongerm-cell origin include tumors derived
from malignant epithelial elements, including adenocarcinoma,[103]
cystadenocarcinoma, endometrioid tumors, clear cell tumors, and
undifferentiated carcinomas. Treatment is stage related and may include
radiation and chemotherapy with cisplatin, carboplatin, etoposide, topotecan,
taxol, and other agents. Refer to the PDQ summaries on adult Ovarian Cancer
Treatment for more information.
Juvenile granulosa cell tumor (JGCT) of the ovary is one of the rare sex
cord/stromal tumors of the ovary seen in girls under 18 years old (median age
7.6 yr.; range 6 months to 17.5 years in one study).[104] They represent about
5% of ovarian tumors in children and adolescents and are distinct from the
granulosa cell tumors seen in adults.[105-107] The majority of patients
present with precocious puberty. Other presenting symptoms include abdominal
pain, abdominal mass, and ascites. JGCT has been reported in children with
Ollier's disease and Maffuci syndrome.[108] Up to 90% of children will have
low stage disease (FIGO [International Federation of Gynecology and Obstetrics]
stage I) and are usually curable with unilateral salpingo-oophorectomy alone.
Patients with advanced disease (FIGO stage II-IV) and those with high mitotic
activity tumors have a poorer prognosis. Use of a cisplatin-based chemotherapy
regimen has been reported in both the adjuvant and recurrent disease settings
with some success.[104,107,109]
-- OTHER RARE CHILDHOOD CANCERS --
Other rare childhood cancers include multiple endocrine neoplasia syndrome,
skin cancer, clear cell sarcoma of tendon sheaths, and cancer of unknown
primary site. The prognosis, diagnosis, classification, and treatment of these
other rare childhood cancers are discussed below.
-- Multiple Endocrine Neoplasia Syndrome --
These syndromes are familial disorders that are characterized by neoplastic
changes in more than one endocrine organ.[87] Changes may include hyperplasia,
benign adenomas, and carcinomas. There are distinct genetic disorders with
characteristic clinical presentations referred to as MEN-1, MEN-2a, and MEN-2b.
An additional complex is referred to as the Carney complex, which is an
association of multiple endocrine neoplasia associated with heart and skin
tumors.[110-112]
The MEN-1 syndrome, also referred to as Werner's syndrome,[113] may involve
tumors of the pituitary gland, the parathyroid, adrenal, and gastric and
pancreatic structures, which may secrete hormones such as insulin. The gene
for this syndrome is located on chromosome 11q13. The MEN-2a syndrome (Sipple
syndrome) is associated with medullary thyroid carcinoma, parathyroid
hyperplasia, adenomas, and pheochromocytoma. The MEN-2b syndrome is associated
with medullary thyroid carcinoma, parathyroid hyperplasia, adenomas, and
pheochromocytoma, mucosal neuromas, and ganglioneuromas.[114] Patients with
the MEN-2b syndrome may have a slender body build, long and thin extremities, a
high arch palate, and pectus excavatum or pes cavus. The face may be
characterized by thick lips because of mucosal neuromas. Such patients can
also be identified by performing a pentagastrin stimulation test or by genetic
screening in families known to be affected. In this syndrome, medullary
thyroid carcinoma may be particularly aggressive; therefore, the thyroid should
be removed by age 5 or 6 years in affected individuals.[115,116]
The Carney complex includes the association of primary pigmented nodular
adrenocortical disease with blue nevi of the skin and mucosa and a variety of
additional endocrine or non-endocrine tumors. There may be myxomas of the skin
or breast and tumors of peripheral nerve sheath origin.[110-112] The outcome
of patients with the MEN-1 syndrome is generally good provided adequate
treatment can be obtained for parathyroid, pancreatic, and pituitary tumors.
The outcome for patients with the MEN-2a syndrome is also generally good, yet
the possibility exists for recurrence of medullary thyroid carcinoma and
pheochromocytoma.[115-117] For patients with the Carney complex, prognosis
depends on the frequency of recurrences of cardiac and skin myxomas and other
tumors.
-- Skin Cancer (Melanoma, Basal Cell and Squamous Cell Carcinoma) --
Melanoma is thought to be the most common skin cancer in children, followed by
basal cell and squamous cell carcinomas.[118-122] The incidence of melanoma in
children and adolescents represents approximately 1% of the new cases of
melanoma that are diagnosed annually in this country. In all instances,
melanoma in the pediatric population is similar to that of adults in relation
to site of presentation, symptoms, description, spread, and prognosis.
The greatest cause of skin cancer of any type is exposure to the ultraviolet
(UV) portion of sunlight.[123-126] Other causes may be related to chemical
carcinogenesis, radiation exposure, immunodeficiency, or immunosuppression.
The person who is most likely to develop a melanoma is easily sunburned, has
poor tanning ability, and generally has light hair, blue eyes, and pale skin.
Worldwide, there is an increasing incidence of both melanoma and nonmelanoma
skin cancers. Melanoma presents as a relatively flat, dark-colored lesion,
which may enlarge, penetrate the skin, or metastasize.
Melanomas may be congenital.[121] They are sometimes associated with large
congenital black spots known as melanocytic nevi, which may cover the trunk and
thigh. Melanomas can also develop in individuals with xeroderma pigmentosum, a
rare recessive disorder characterized by extreme sensitivity to sunlight,
keratosis, and various neurologic manifestations. Individuals with xeroderma
pigmentosum may also develop other skin cancers, including squamous and basal
cell carcinomas.[122] Children with hereditary immunodeficiencies have an
increased lifetime risk of developing melanoma.
Neurocutaneous melanosis is an unusual condition associated with large or
multiple congenital nevi of the skin and melanin deposits within the central
nervous system. These deposits may be detected by magnetic resonance imaging
of the brain or spinal cord. Dysplastic nevi occur in about 5% of the U.S.
population and are potential precursors of melanoma.[122] Individuals with
atypical moles, which include raised lesions (that may bleed) and various color
hues (brown, tan, pink, black), are at an increased risk of having melanoma and
of having children affected by these premalignant lesions.
Basal cell carcinomas generally appear as raised lumps or ulcerated lesions,
usually in areas with previous sun exposure. These tumors may be multiple and
exacerbated by radiation therapy as delivered for medulloblastoma.[127,128]
Squamous cell carcinomas are usually reddened lesions with varying degrees of
scaling or crusting, and they have an appearance similar to eczema, infections,
trauma, or psoriasis.[129]
Biopsy or excision is necessary to determine the diagnosis of any skin cancer.
Diagnosis is necessary for decisions regarding additional treatment. Basal and
squamous cell carcinomas are generally curable with surgery alone, but the
treatment of melanoma requires greater consideration because of its potential
for metastasis. Surgery for melanoma depends on the size, site, level of
invasion, and metastatic extent or stage of the tumor.[122] Wide excision with
skin grafting may become necessary. It is currently recommended that surgical
resection include a 2-cm-deep margin for melanoma lesions, with examination of
the regional lymph nodes draining the site of the melanoma. This procedure may
require the injection of a radioisotope, following its distribution, and then
performing excision of the associated regional lymph nodes (sentinel node
biopsy technique). This requires injection of a vital blue stain and
radioisotope into the skin to characterize the pattern of lymph node drainage.
Lymph node dissection is necessary if sentinel nodes are involved with the
tumor; however, if there is no spread of the disease beyond the lymph nodes,
adjuvant therapy with interferon alfa-2b alone may be recommended for a period
of 1 year.[122] For individuals with metastatic disease, a combination of
cisplatin, vinblastine, imidazole carboxamide, interleukin-2, and interferon
alfa-2b has been proposed.[122] Prognosis for melanoma in children and
adolescents is similar to that for adults with similar stage disease, with the
prognosis depending on the tumor thickness and the extent of spread at the time
of diagnosis.[130,131] Survival decreases with greater depth of invasion and
with metastases to lymph nodes. Refer to the PDQ summary on adult Skin Cancer
Treatment for more information.
-- Clear Cell Sarcoma of Tendon Sheaths --
Malignant melanoma of soft parts has been described as "clear cell sarcoma of
tendons and aponeuroses."[132] Because of its association with tenosynovial
structures and its derivation from neuroectoderm, malignant melanoma of soft
parts shares a number of features with cutaneous melanoma, as has been shown by
immunophenotyping and structural similarities. More than 95% of these tumors
present in the extremities. Survival with this tumor has been correlated with
tumor size and other microscopic features. Cytogenetic studies of these tumors
have noted a specific chromosome abnormality. Treatment includes surgical
removal, radiation therapy, and chemotherapy similar to that given for soft
tissue sarcomas.
-- Cancer of Unknown Primary Site --
These cancers present as a metastatic cancer for which a precise primary tumor
site cannot be determined.[133] As an example, lymph nodes at the base of the
skull may enlarge in relationship to a tumor that may be on the face or the
scalp but is not evident by physical examination or by radiographic imaging.
Thus, modern imaging techniques may indicate the extent of the disease but not
a primary site. Tumors such as adenocarcinoma, melanoma, and embryonal tumors
such as rhabdomyosarcoma and neuroblastoma may have such a presentation.
For all patients who present with tumors from an unknown primary site, the
treatment should be considered in relation to the pathology of the tumor and
should be appropriate for the general type of cancer initiated, irrespective of
the site or sites of involvement.[133] Chemotherapy and radiation therapy
treatments appropriate and relevant for the general category of carcinoma or
sarcoma (depending upon the histologic findings, symptoms, and extent of tumor)
should be initiated as early as possible.
References:
1. Sanders J, Glader B, Cairo M, et al.: Guidelines for the pediatric cancer
center and role of such centers in diagnosis and treatment. American
Academy of Pediatrics Section Statement Section on Hematology/Oncology.
Pediatrics 99(1): 139-141, 1997.
2. Vasef MA, Ferlito A, Weiss LM: Nasopharyngeal carcinoma, with emphasis on
its relationship to Epstein-Barr virus. Annals of Otology, Rhinology,
and Laryngology 106(4): 348-356, 1997.
3. Young JL Jr, Miller RW: Incidence of malignant tumors in U.S. children.
Journal of Pediatrics 86(2): 254-258, 1975.
4. Naegele RF, Champion J, Murphy S, et al.: Nasopharyngeal carcinoma in
American children: Epstein-Barr virus-specific antibody titers and
prognosis. International Journal of Cancer 29(2): 209-212, 1982.
5. Beahrs OH, Henson DE, Hutter RP, Myers MH, eds.: American Joint
Committee on Cancer: Manual for Staging of Cancer. 5th ed.,
Philadelphia, Pa: JB Lippincott, 1997.
6. Casanova M, Ferrari A, Gandola L, et al.: Undifferentiated nasopharyngeal
carcinoma in children and adolescents: comparison between staging
systems. Annals of Oncology 12(8): 1157-1162, 2001.
7. Martin WD, Shah KJ: Carcinoma of the nasopharynx in young patients.
International Journal of Radiation Oncology, Biology, Physics 28(4):
991-999, 1994.
8. Al-Sarraf M, LeBlanc M, Giri PG, et al.: Chemoradiotherapy versus
radiotherapy in patients with advanced nasopharyngeal cancer: phase III
randomized Intergroup study 0099. Journal of Clinical Oncology 16(4):
1310-1317, 1998.
9. Mertens R, Granzen B, Lassay L, et al.: Nasopharyngeal carcinoma in
childhood and adolescence. Concept and preliminary results of the
Cooperative GPOH study NPC-91. Cancer 80(5): 951-959, 1997.
10. Douglass EC, Fontanesi J, Ribeiro RC, et al.: Improved long-term
disease-free survival in nasopharyngeal carcinoma (NPC) in childhood and
adolescence: a multi-institution treatment protocol. Proceedings of the
American Society of Clinical Oncology 15: A1470, 467, 1996.
11. Wolden SL, Steinherz PG, Kraus DH, et al.: Improved long-term survival
with combined modality therapy for pediatric nasopharynx cancer.
International Journal of Radiation Oncology, Biology, Physics 46(4):
859-864, 2000.
12. Geiger JD, Thompson NW: Thyroid tumors in children. Otolaryngologic
Clinics of North America 29(4): 711-719, 1996.
13. Feinmesser R, Lubin E, Segal K, et al.: Carcinoma of the thyroid in
children--a review. Journal of Pediatric Endocrinology and Metabolism
10(6): 561-568, 1997.
14. Cotterill SJ, Pearce MS, Parker L: Thyroid cancer in children and young
adults in the North of England. Is increasing incidence related to the
Chernobyl accident? European Journal of Cancer 37(8): 1020-1026, 2001.
15. Flannery TK, Kirkland JL, Copeland KC, et al.: Papillary thyroid cancer:
a pediatric perspective. Pediatrics 98(3 pt 1): 464-466, 1996.
16. Kaplan MM, Garnick MB, Gelber R, et al.: Risk factors for thyroid
abnormalities after neck irradiation for childhood cancer. American
Journal of Medicine 74(2): 272-280, 1983.
17. Hill CS, Ibanez ML, Samaan NA, et al.: Medullary (solid) carcinoma of the
thyroid gland: an analysis of the M.D. Anderson Hospital experience with
patients with the tumor, its special features, and its histogenesis.
Medicine 52(2): 141-171, 1973.
18. Krueger JE, Maitra A, Albores-Saavedra J: Inherited medullary
microcarcinoma of the thyroid: a study of 11 cases. American Journal of
Surgical Pathology 24(6): 853-858, 2000.
19. Vassilopoulou-Sellin R: Childhood thyroid cancer outcome and mortality.
Oncology Case Reports & Review 13(1): 1-7, 1998.
20. Yeh SD, La Quaglia MP: 131I therapy for pediatric thyroid cancer.
Seminars in Pediatric Surgery 6(3): 128-133, 1997.
21. Vassilopoulou-Sellin R, Goepfert H, Raney B, et al.: Differentiated
thyroid cancer in children and adolescents: clinical outcome and
mortality after long-term follow-up. Head and Neck 20(6): 549-555,
1998.
22. Alessandri AJ, Goddard KJ, Blair GK, et al.: Age is the major determinant
of recurrence in pediatric differentiated thyroid carcinoma. Medical
and Pediatric Oncology 35(1): 41-46, 2000.
23. Stellman SD, Resnicow K: Tobacco smoking, cancer and social class. In:
Kogevinas M, Pearce N, eds.: Social Inequalities and Cancer. Lyon,
France: International Agency for Research on Cancer, IARC No. 138, 1997,
pp 229-250.
24. Kahn MA: Ameloblastoma in young persons: a clinicopathologic analysis and
etiologic investigation. Oral Surgery, Oral Medicine, and Oral
Pathology 67(6): 706-715, 1989.
25. Johns ME, Goldsmith MM: Incidence, diagnosis, and classification of
salivary gland tumors. Oncology (Huntington NY) 3(2): 47-62, 1989.
26. Kaste SC, Hedlund G, Pratt CB: Malignant parotid tumors in patients
previously treated for childhood cancer: clinical and imaging findings
in eight cases. American Journal of Roentgenology 162(3): 655-659,
1994.
27. Kamal SA, Othman EO: Diagnosis and treatment of parotid tumours. Journal
of Laryngology and Otology 111(4): 316-321, 1997.
28. Rogers DA, Rao BN, Bowman L, et al.: Primary malignancy of the salivary
gland in children. Journal of Pediatric Surgery 29(1): 44-47, 1994.
29. Bentz BG, Hughes CA, Ludemann JP, et al.: Masses of the salivary gland
region in children. Archives of Otolaryngology, Head and Neck Surgery
126(12): 1435-1439, 2000.
30. McGuirt WF Jr., Little JP: Laryngeal cancer in children and adolescents.
Otolaryngologic Clinics of North America 30(2): 207-214, 1997.
31. Bauman NM, Smith RJ: Recurrent respiratory papillomatosis. Pediatric
Clinics of North America 43(6): 1385-1401, 1996.
32. Kashima HK, Mounts P, Shah K: Recurrent respiratory papillomatosis.
Obstetrics and Gynecology Clinics of North America 23(3): 699-706, 1996.
33. Avidano MA, Singleton GT: Adjuvant drug strategies in the treatment of
recurrent respiratory papillomatosis. Otolaryngology - Head and Neck
Surgery 112(2): 197-202, 1995.
34. Serour F, Gilad A, Kopolovic J, et al.: Secretory breast cancer in
childhood and adolescence: report of a case and review of the
literature. Medical and Pediatric Oncology 20(4): 341-344, 1992.
35. Drukker BH: Breast disease: a primer on diagnosis and management.
International Journal of Fertility 42(5): 278-287, 1997.
36. Rogers DA, Lobe TE, Rao BN, et al.: Breast malignancy in children.
Journal of Pediatric Surgery 29(1): 48-51, 1994.
37. Kaste SC, Hudson MM, Jones DJ, et al.: Breast masses in women treated for
childhood cancer. Cancer 82(4): 784-792, 1998.
38. Vadasz P, Palffy G, Egervary M, et al.: Diagnosis and treatment of
bronchial carcinoid tumors: clinical and pathological review of 120
operated patients. European Journal of Cardio-thoracic Surgery 7(1):
8-11, 1993.
39. Kulke MH, Mayer RJ: Carcinoid tumors. New England Journal of Medicine
340(11): 858-868, 1999.
40. Oliaro A, Filosso PL, Donati G, et al.: Atypical bronchial carcinoids.
Review of 46 patients. Journal of Cardiovascular Surgery 41(1):
131-135, 2000.
41. Indolfi P, Casale F, Carli M, et al.: Pleuropulmonary blastoma.
Management and prognosis of 11 cases. Cancer 89(6): 1396-1401, 2000.
42. Wright JR Jr: Pleuropulmonary blastoma: a case report documenting
transition from type I (cystic) to type III (solid). Cancer 88(12):
2853-2858, 2000.
43. Schmaltz C, Sauter S, Opitz O, et al.: Pleuro-pulmonary blastoma: a case
report and review of the literature. Medical and Pediatric Oncology
25(6): 479-484, 1995.
44. Priest JR, Watterson J, Strong L, et al.: Pleuropulmonary blastoma: a
marker for familial disease. Journal of Pediatrics 128(2): 220-224,
1996.
45. Gangopadhyay AN, Mohanty PK, Gopal SC, et al.: Adenocarcinoma of the
esophagus in an 8-year-old boy. Journal of Pediatric Surgery 32(8):
1259-1260, 1997.
46. Verley JM, Hollmann KH: Thymoma. A comparative study of clinical stages,
histologic features, and survival in 200 cases. Cancer 55(5):
1074-1086, 1985.
47. Furman WL, Buckley PJ, Green AA, et al.: Thymoma and myasthenia gravis in
a 4-year-old child. Case report and review of the literature. Cancer
56(11): 2703-2706, 1985.
48. Souadjian JV, Enriques P, Silverstein MN, et al.: The spectrum of
diseases associated with thymoma. Coincidence or syndrome? Archives of
Internal Medicine 134(2): 374-379, 1974.
49. Cowen D, Richaud P, Mornex F, et al.: Thymoma: results of a multicentric
retrospective series of 149 non-metastatic irradiated patients and
review of the literature. Radiotherapy and Oncology 34(1): 9-16, 1995.
50. Carlson RW, Dorfman RF, Sikic BI: Successful treatment of metastatic
thymic carcinoma with cisplatin, vinblastine, bleomycin, and etoposide
chemotherapy. Cancer 66(10): 2092-2094, 1990.
51. Niehues T, Harms D, Jurgens H, et al.: Treatment of pediatric malignant
thymoma: long-term remission in a 14-year-old boy with EBV-associated
thymic carcinoma by aggressive, combined modality treatment. Medical
and Pediatric Oncology 26(6): 419-424, 1996.
52. Chan HS, Sonley MJ, Moes CA, et al.: Primary and secondary tumors of
childhood involving the heart, pericardium, and great vessels. A report
of 75 cases and review of the literature. Cancer 56(4): 825-836, 1985.
53. Michler RE, Goldstein DJ: Treatment of cardiac tumors by orthotopic
cardiac transplantation. Seminars in Oncology 24(5): 534-539, 1997.
54. Stiller B, Hetzer R, Meyer R, et al.: Primary cardiac tumours: when is
surgery necessary? European Journal of Cardio-thoracic Surgery 20(5):
1002-1006, 2001.
55. Kelsey A: Mesothelioma in childhood. Pediatric Hematology and Oncology
11(5): 461-462, 1994.
56. Hofmann J, Mintzer D, Warhol MJ: Malignant mesothelioma following
radiation therapy. American Journal of Medicine 97(4): 379-382, 1994.
57. Pappo AS, Santana VM, Furman WL, et al.: Post-irradiation malignant
mesothelioma. Cancer 79(1): 192-193, 1997.
58. Hyers TM, Ohar JM, Crim C: Clinical controversies in asbestos-induced
lung diseases. Seminars in Diagnostic Pathology 9(2): 97-101, 1992.
59. Wall JE, Mandrell BN, Jenkins JJ III, et al.: Effectiveness of paclitaxel
in treating papillary serous carcinoma of the peritoneum in an
adolescent. American Journal of Obstetrics and Gynecology 172(3):
1049-1052, 1995.
60. Abramson SJ: Adrenal neoplasms in children. Radiologic Clinics of North
America 35(6): 1415-1453, 1997.
61. Li FP, Fraumeni JF Jr., Mulvihill JJ, et al.: A cancer family syndrome in
twenty-four kindreds. Cancer Research 48(18): 5358-5362, 1988.
62. DeBaun MR, Tucker MA: Risk of cancer during the first four years of life
in children from The Beckwith-Wiedemann Syndrome Registry. Journal of
Pediatrics 132(3, pt 1): 398-400, 1998.
63. Hoyme HE, Seaver LH, Jones KL, et al.: Isolated hemihyperplasia
(hemihypertrophy): report of a prospective multicenter study of the
incidence of neoplasia and review. American Journal of Medical Genetics
79(4): 274-278, 1998.
64. Bugg MF, Ribeiro RC, Roberson PK, et al.: Correlation of pathologic
features with clinical outcome in pediatric adrenocortical neoplasia. A
study of a Brazilian population. American Journal of Clinical Pathology
101(5): 625-629, 1994.
65. Sandrini R, Ribeiro RC, DeLacerda L: Childhood Adrenocortical tumors.
Journal of Clinical Endocrinology and Metabolism 82(7): 2027-2031, 1997.
66. Mayer SK, Oligny LL, Deal C, et al.: Childhood adrenocortical tumors:
case series and reevaluation of prognosis--a 24-year experience.
Journal of Pediatric Surgery 32(6): 911-915, 1997.
67. Fiori E, Leone G, Gazzanelli S, et al.: Renal cell carcinoma in
adolescents. A case report and review of the literature. Panminerva
Medica 38(2): 121-128, 1996.
68. Carcao MD, Taylor GP, Greenberg ML, et al.: Renal-cell carcinoma in
children: a different disorder from its adult counterpart? Medical and
Pediatric Oncology 31(3): 153-158, 1998.
69. Bleggi-Torres LF, De Noranha L, Fillus NJ, et al.: Von Hippel-Lindau's
disease: report of three cases and review of the literature. Arquivos
de Neuro-Psiquiatria 53(4): 782-788, 1995.
70. Raney RB Jr., Palmer N, Sutow WW, et al.: Renal cell carcinoma in
children. Medical and Pediatric Oncology 11(2): 91-98, 1983.
71. Wang N, Perkins KL: Involvement of band 3p14 in t(3;8) hereditary renal
carcinoma. Cancer Genetics and Cytogenetics 11(4): 479-481, 1984.
72. Eble JN: Angiomyolipoma of kidney. Seminars in Diagnostic Pathology
15(1): 21-40, 1998.
73. Argani P, Antonescu CR, Illei PB, et al.: Primary renal neoplasms with
the ASPL-TFE3 gene fusion of alveolar soft part sarcoma. A distinctive
tumor entity previously included among renal cell carcinomas of children
and adolescents. American Journal of Pathology 159(1): 179-192, 2001.
74. Fyfe G, Fisher RI, Rosenberg SA, et al.: Results of treatment of 255
patients with metastatic renal cell carcinoma who received high-dose
recombinant interleukin-2 therapy. Journal of Clinical Oncology 13(3):
688-696, 1995.
75. American Cancer Society: Cancer Facts and Figures-2000. Atlanta, Ga:
American Cancer Society, 2000.
76. Rowland M, Drumm B: Helicobacter pylori infection and peptic ulcer
disease in children. Current Opinion in Pediatrics 7(5): 553-559, 1995.
77. Ajani JA: Current status of therapy for advanced gastric carcinoma.
Oncology (Huntington NY) 12(8 suppl 6): 99-102, 1998.
78. Schwartz MG, Sgaglione NA: Gastric carcinoma in the young: overview of
the literature. The Mount Sinai Journal of Medicine 51(6): 720-723,
1984.
79. Vossen S, Goretzki PE, Goebel U, et al.: Therapeutic management of rare
malignant pancreatic tumors in children. World Journal of Surgery
22(8): 879-882, 1998.
80. Schwartz MZ: Unusual peptide-secreting tumors in adolescents and
children. Seminars in Pediatric Surgery 6(3): 141-146, 1997.
81. Murakami T, Ueki K, Kawakami H, et al.: Pancreatoblastoma: case report
and review of treatment in the literature. Medical and Pediatric
Oncology 27(3): 193-197, 1996.
82. Imamura A, Nakagawa A, Okuno M, et al.: Pancreatoblastoma in an
adolescent girl: case report and review of 26 Japanese cases. European
Journal of Surgery 164(4): 309-312, 1998.
83. Defachelles AS, de Lassalle EM, Boutard P, et al.: Pancreatoblastoma in
childhood: clinical course and therapeutic management of seven patients.
Medical and Pediatric Oncology 37(1): 47-52, 2001.
84. Correa P, Haenszel W: The epidemiology of large-bowel cancer. Advances
in Cancer Research 26: 1-141, 1978.
85. Sherlock P, Lipkin M, Winawer SJ: Predisposing factors in carcinoma of
the colon. Advances in Internal Medicine 20: 121-150, 1975.
86. Lynch HT, Fusaro RM, Lynch JF: Cancer genetics in the new era of
molecular biology. Annals of the New York Academy of Sciences 833:
1-28, 1997.
87. Dean PA: Hereditary intestinal polyposis syndromes. Revista de
Gastroenterolgia de Mexico 61(2): 100-111, 1996.
88. Turcot J, Despres JP, St. Pierre F: Malignant tumors of the central
nervous system associated with familial polyposis of the colon: Report
of two cases. Diseases of the Colon and Rectum 2: 465-468, 1959.
89. Vogelstein B, Fearon ER, Hamilton SR, et al.: Genetic alterations during
colorectal-tumor development. New England Journal of Medicine 319(9):
525-532, 1988.
90. Pratt CB, Jane JA: Multiple colorectal carcinomas, polyposis coli, and
neurofibromatosis, followed by multiple glioblastoma multiforme.
Journal of the National Cancer Institute 83(12): 880-881, 1991.
91. Pratt CB, Rao BN, Merchant TE, et al.: Treatment of colorectal carcinoma
in adolescents and young adults with surgery,
5-fluorouracil/leucovorin/interferon-alfa 2a and radiation therapy.
Medical and Pediatric Oncology 32(6): 459-460, 1999.
92. Kauffman, WM, Jenkins JJ III, Helton K, et al.: Imaging features of
ovarian metastases from colonic adenocarcioma in adolescents. Pediatric
Radiology 25(4): 286-288, 1995.
93. Madajewicz S, Petrelli N, Rustum YM, et al.: Phase I-II trial of
high-dose calcium leucovorin and 5-fluorouracil in advanced colorectal
cancer. Cancer Research 44(10): 4667-4669, 1984.
94. Wolmark N, Bryant J, Smith R, et al.: Adjuvant 5-fluorouracil and
leucovorin with or without interferon alfa-2a in colon carcinoma:
National Surgical Adjuvant Breast and Bowel Project protocol C-05.
Journal of the National Cancer Institute 90(23): 1810-1816, 1998.
95. Modlin IM, Sandor A: An analysis of 8305 cases of carcinoid tumors.
Cancer 79(4): 813-829, 1997.
96. Deans GT, Spence RA: Neoplastic lesions of the appendix. British Journal
of Surgery 82(3): 299-306, 1995.
97. Doede T, Foss HD, Waldschmidt J: Carcinoid tumors of the appendix in
children - epidemiology, clinical aspects and procedure. European
Journal of Pediatric Surgery 10(6): 372-377, 2000.
98. Tormey WP, FitzGerald RJ: The clinical and laboratory correlates of an
increased urinary 5-hydroxyindoleacetic acid. Postgraduate Medical
Journal 71(839): 542-545, 1995.
99. Pelizzo G, La Riccia A, Bouvier R, et al.: Carcinoid tumors of the
appendix in children. Pediatric Surgery International 17(5-6): 399-402,
2001.
100. Hoenig DM, McRae S, Chen SC, et al.: Transitional cell carcinoma of the
bladder in the pediatric patient. Journal of Urology 156(1): 203-205,
1996.
101. Johansson SL, Cohen SM: Epidemiology and etiology of bladder cancer.
Seminars in Surgical Oncology 13(5): 291-298, 1997.
102. IARC Working Group on the Evaluation of Carcinogenic Risks to Humans.
International Agency for Research on Cancer: Overall evaluations of
carcinogenicity: an updating of IARC monographs, volumes 1 to 42. IARC
Monographs on the Evaluation of Carcinogenic Risks to Humans, Supplement
7. Lyon, France: International Agency for Research on Cancer, 1987.
103. Lovvorn HN III, Tucci LA, Stafford PW: Ovarian masses in the pediatric
patient. AORN Journal 67(3): 568-576, 1998.
104. Calaminus G, Wessalowski R, Harms D, et al.: Juvenile granulosa cell
tumors of the ovary in children and adolescents: results from 33
patients registered in a prospective cooperative study. Gynecologic
Oncology 65(3): 447-452, 1997.
105. Bouffet E, Basset T, Chetail N, et al.: Juvenile granulosa cell tumor of
the ovary in infants: a clinicopathologic study of three cases and
review of the literature. Journal of Pediatric Surgery 32(5): 762-765,
1997.
106. Zaloudek C, Norris HJ: Granulosa tumors of the ovary in children.
American Journal of Surgical Pathology 6(6): 503-512, 1982.
107. Vassal G, Flamant F, Caillaud JM, et al.: Juvenile granulosa cell tumor
of the ovary in children: a clinical study of 15 cases. Journal of
Clinical Oncology 6(6): 990-995, 1988.
108. Gell JS, Stannard MW, Ramnani DM, et al.: Juvenile granulosa cell tumor
in a 13-year-old girl with enchondromatosis (Ollier's disease): a case
report. Journal of Pediatric and Adolescent Gynecology 11(3): 147-150,
1998.
109. Powell JL, Connor GP, Henderson GS: Management of recurrent juvenile
granulosa cell tumor of the ovary. Gynecologic Oncology 81(1): 113-116,
2001.
110. Carney JA, Go VL, Sizemore GW, et al.: Alimentary-tract
ganglioneuromatosis: A major component of the syndrome of multiple
endocrine neoplasia, type 2b. New England Journal of Medicine 295(23):
1287-1291, 1976.
111. Carney JA, Go VL, Gordon H, et al.: Familial pheochromocytoma and islet
cell tumor of the pancreas. American Journal of Medicine 68(4):
515-521, 1980.
112. Carney JA, Young WF: Primary pigmented nodular adrenocortical disease and
its associated conditions. Endocrinologist 2: 6-21, 1992.
113. Werner P: Endocrine adenomatosis and peptic ulcer in a large kindred:
Inherited multiple tumors and mosaic pleiotropism in man. American
Journal of Medicine 35(2): 205-212, 1963.
114. Skinner MA, DeBenedetti MK, Moley JF, et al.: Medullary thyroid carcinoma
in children with multiple endocrine neoplasia types 2A and 2B. Journal
of Pediatric Surgery 31(1): 177-182, 1996.
115. Lallier M, St-Vil D, Giroux M, et al.: Prophylactic thyroidectomy for
medullary thyroid carcinoma in gene carriers of MEN2 syndrome. Journal
of Pediatric Surgery 33(6): 846-848, 1998.
116. Dralle H, Gim O, Simon D, et al.: Prophylactic thyroidectomy in 75
children and adolescents with hereditary medullary thyroid carcinoma:
German and Austrian experience. World Journal of Surgery 22(7):
744-751, 1998.
117. Skinner MA, Wells SA Jr: Medullary carcinoma of the thyroid gland and the
MEN 2 syndromes. Seminars in Pediatric Surgery 6(3): 134-140, 1997.
118. Sasson M, Mallory SB: Malignant primary skin tumors in children. Current
Opinion in Pediatrics 8(4): 372-377, 1996.
119. Barnhill RL: Childhood melanoma. Seminars in Diagnostic Pathology 15(3):
189-194, 1998.
120. Ruiz-Maldonado R, Orozco-Covarrubias ML: Malignant melanoma in children.
A review. Archives of Dermatology 133(3): 363-371, 1997.
121. Pratt CB, Palmer MK, Thatcher N, et al.: Malignant melanoma in children
and adolescents. Cancer 47(2): 392-397, 1981.
122. Ceballos PI, Ruiz-Maldonado R, Mihm MC Jr: Melanoma in children. New
England Journal of Medicine 332(10): 656-662, 1995.
123. Pappo AS, Kaste SC, Rao BN, et al.: Childhood melanoma. In: Balch CM,
Houghton AN, Sober AJ, et al., eds.: Cutaneous Melanoma. 3rd ed., St.
Louis, Mo: Quality Medical Publishing Inc., 1998, pp 175-186.
124. Heffernan AE, O'Sullivan A: Pediatric sun exposure. Nurse Practitioner
23(7): 67-68, 71-78, 83-86, 1998.
125. Berg P, Lindelof B: Differences in malignant melanoma between children
and adolescents. A 35-year epidemiological study. Archives of
Dermatology 133(3): 295-297, 1997.
126. Elwood JM, Jopson J: Melanoma and sun exposure: An overview of published
studies. International Journal of Cancer 73(2): 198-203, 1997.
127. Garcia-Silva J, Velasco-Benito JA, Pena-Penabad C, et al.: Basal cell
carcinoma in a girl after cobalt irradiation to the cranium for acute
lymphoblastic leukemia: case report and literature review. Pediatric
Dermatology 13(1): 54-57, 1996.
128. Gorlin RJ: Nevoid basal cell carcinoma syndrome. Dermatologic Clinics
13(1): 113-125, 1995.
129. Kimonis VE, Goldstein AM, Pastakia B, et al.: Clinical manifestations in
105 persons with nevoid basal cell carcinoma syndrome. American Journal
of Medical Genetics 69: 299-308, 1997.
130. Gibbs P, Moore A, Robinson W, et al.: Pediatric melanoma: are recent
advances in the management of adult melanoma relevant to the pediatric
population. Journal of Pediatric Hematology/Oncology 22(5): 428-432,
2000.
131. Conti EM, Cercato MC, Gatta G, et al.: Childhood melanoma in Europe since
1978: a population-based survival study. European Journal of Cancer
37(6): 780-784, 2001.
132. Hicks MJ, Saldivar VA, Chintagmapala MM, et al.: Malignant melanoma of
soft parts involving the head and neck region: review of literature and
case report. Ultrastructural Pathology 19(5): 395-400, 1995.
133. Kuttesch JF Jr, Parham DM, Kaste SC, et al.: Embryonal malignancies of
unknown primary origin in children. Cancer 75(1): 115-121, 1995.
Date Last Modified: 07/2002
******************************************************************************
* This information from PDQ is reviewed regularly by members of the PDQ *
* Editorial Boards. If you have specific comments on the content of this *
* information, direct them to: PDQ Editorial Board, CIPS/NCI, 6116 *
* Executive Boulevard, Suite 3002B, MSC-8321, 20892-8321, fax: 301-480-8105.*
* *
* The PDQ database also contains listings of clinical trial protocols and *
* directories of organizations and physicians who treat cancer patients, *
* but this information is not available through CancerMail. For more *
* information on accessing PDQ, consult the CancerMail Contents List. *
******************************************************************************
|
[Home] | [Search] | [Medical Q&A Forums] | [Patient Network] |
This information has been brought to you by
Med Help International,
licenced by the National Cancer Institute as a distributor of CancerNet.