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One of the first signs of testicular cancer is often a lump or swelling in the testes. The U.S. Preventive Services Task Force (USPSTF) recommends against routine screening for testicular cancer in asymptomatic adolescent and adults including routine testicular self-exams. However, the American Cancer Society suggests that some men should examine their testicles monthly, especially if they have a family history of cancer, and the American Urological Association recommends monthly testicular self-examinations for all young men.
Symptoms may also include one or more of the following:
- a lump in one testis which may or may not be painful
- sharp pain or a dull ache in the lower abdomen or scrotum
- a feeling often described as "heaviness" in the scrotum
- breast enlargement (gynecomastia) from hormonal effects of β-hCG
- low back pain (lumbago) due to the cancer spreading to the lymph nodes along the back
It is not very common for testicular cancer to spread to other organs, apart from the lungs. If it has, however, the following symptoms may be present:
- shortness of breath (dyspnea), cough or coughing up blood (hemoptysis) from metastatic spread to the lungs
- a lump in the neck due to metastases to the lymph nodes
Testicular cancer, cryptorchidism, hypospadias, and poor semen quality make up the syndrome known as testicular dysgenesis syndrome.
Although testicular cancer can be derived from any cell type found in the testicles, more than 95% of testicular cancers are germ cell tumors (GCTs). Most of the remaining 5% are sex cord-gonadal stromal tumours derived from Leydig cells or Sertoli cells. Correct diagnosis is necessary to ensure the most effective and appropriate treatment. To some extent, this can be done via blood tests for tumor markers, but definitive diagnosis requires examination of the histology of a specimen by a pathologist.
Most pathologists use the World Health Organization classification system for testicular tumors:
- Germ cell tumors
- "Precursor lesions"
- Intratubular germ cell neoplasia
- Unclassified type (carcinoma in situ)
- Specified types
- "Tumors of one histologic type (pure forms)"
- Seminoma
- Variant - Seminoma with syncytiotrophoblastic cells
- Spermatocytic seminoma
- Variant - spermatocytic seminoma with sarcoma
- Embryonal carcinoma
- Yolk sac tumor
- Trophoblastic tumors
- Choriocarcinoma
- Variant - monophasic choriocarcinoma
- Placental site trophoblastic tumour
- Cystic trophoblastic tumor
- Teratoma
- Variant - Dermoid cyst
- Variant - Epidermoid cyst
- Variant - Monodermal teratoma (Carcinoid, Primitive neuroectodermal tumor (PNET), Nephroblastoma-like tumor, others.
- Variant - Teratomic with somatic-type malignancy
- "Tumours of more than one histologic type (mixed forms)"
- Embryonal carcinoma and teratoma
- Teratoma and seminoma
- Choriocarcinoma and teratoma.embryonal carcinoma
- Others
- Sex cord/Gonadal stromal tumors
- Leydig cell tumor
- Sertoli cell tumor
- Lipid rich variant
- Scleriosing variant
- Large cell calcifying variant
- Intratubular sertoli cell neoplasia in Peutz-Jeghers syndrome
- Granulosa cell tumor
- Adult type
- Juvenile type
- Thecoma Fibroma Group
- Thecoma
- Fibroma
- Sex cord/gonadal stromal tumor - incompletely differentiated
- Sex cord/gonadal stromal tumor - mixed types
- Mixed Germ Cell and Sex Cord/Gonadal Stromal Tumors
- Gonadoblastoma
- Germ cell-sex cord/gonadal stromal tumor, unclassified
- Miscellaneous tumours of the testis
- Carcinoid
- Tumors of ovarian epithelial types
- Serous tumor of borderline malignancy
- Serous carcinoma
- Well differentiated endometrioid tumor
- Mucinous cystadenoma
- Mucinous cystadenocarcinoma
- Brenner tumor
- Nephroblastoma
- Paraganglioma
- Haematopoietic tumors
- Tumours of collecting ducts and rete
- Adenoma
- Carcinoma
- Tumors of the paratesticular structures
- Adenomatoid tumor
- Malignant and Benign Mesothelioma
- Adenocarcinoma of the epididymis
- Papillary cystadenoma of the epididymis
- Melanotic neuroectodermal tumor
- Desmoplastic small round cell tumor
- Mesenchymal tumors of the spermatic cord and testicular adnexae
- Lipoma
- Liposarcoma
- Rhabdomyosarcoma
- Aggressive angiomyxoma
- Angiomyofibroblastoma-like tumor (see Myxoma)
- Fibromatosis
- Fibroma
- Solitary fibrous tumor
- Others
- Secondary tumors of the testis
Male breast cancer (male breast neoplasm) is a rare cancer in males that originates from the breast. Many males with breast cancer have inherited a "BRCA" mutation, but there are other causes, including alcohol abuse and exposure to certain hormones and ionizing radiation.
As it presents a similar pathology as female breast cancer, assessment and treatment relies on experiences and guidelines that have been developed in female patients. The optimal treatment is currently not known.
As in females, infiltrating ductal carcinoma is the most common type. While intraductal cancer, inflammatory carcinoma, and Paget's disease of the nipple have been described, lobular carcinoma in situ has not been seen in males. Breast cancer in males spreads via lymphatics and blood stream like female breast cancer. Accordingly, the TNM staging system for breast cancer is the same for males and females.
Size of the lesion and lymph node involvement determine prognosis; thus small lesions without lymph node involvement have the best prognosis. Estrogen receptor and progesterone receptor status and HER2/neu (Human Epidermal Growth Factor Receptor 2) gene amplification need to be reported as they may affect treatment options. About 85% of all male breast cancers are estrogen receptor–positive, and 70% are progesterone receptor–positive.
The symptoms produced by metastatic breast cancer vary by the location of the metastases. For instance:
- Metastatic disease to the bone causes severe, progressive pain, and, less commonly, pathological fracture, erythema over the affected bone, and swelling.
- Metastatic breast cancer to the brain causes the following symptoms: persistent, progressively worsening headache, visual changes, seizures, nausea or vomiting, vertigo, behavioral and personality changes, and increased intracranial pressure.
- Metastatic disease to the liver causes jaundice, elevated liver enzymes, abdominal pain, loss of appetite, nausea, and vomiting
- Metastatic breast cancer to the lung or pleura causes chronic cough, dyspnea, abnormal chest X-ray, and chest pain.
- Other nonspecific systemic symptoms of metastatic breast cancer include fatigue, malaise, weight loss, and poor appetite.
Triple-negative breast cancer (sometimes abbreviated TNBC) refers to any breast cancer that does not express the genes for estrogen receptor (ER), progesterone receptor (PR) or Her2/neu. This makes it more difficult to treat since most hormone therapies target one of the three receptors, so triple-negative cancers often require combination therapies. Triple negative is sometimes used as a surrogate term for basal-like; however, more detailed classification may provide better guidance for treatment and better estimates for prognosis.
Triple-negative breast cancers comprise a very heterogeneous group of cancers. There are conflicting information over prognosis for the various subtypes but it appears that the Nottingham prognostic index is valid and hence general prognosis is rather similar with other breast cancer of same stage, except that more aggressive treatment is required. Some types of triple-negative breast cancer are known to be more aggressive with poor prognosis, while other types have very similar or better prognosis than hormone receptor positive breast cancers. Pooled data of all triple-negative subtypes suggest that with optimal treatment 20-year survival rates are very close to those of hormone positive cancer.
Triple-negative breast cancers have a relapse pattern that is very different from hormone-positive breast cancers: the risk of relapse is much higher for the first 3–5 years but drops sharply and substantially below that of hormone-positive breast cancers after that. This relapse pattern has been recognized for all types of triple-negative cancers for which sufficient data exists although the absolute relapse and survival rates differ across subtypes.
Metastatic breast cancer, also referred to as metastases, advanced breast cancer, secondary tumours, secondaries or stage 4 breast cancer, is a stage of breast cancer where the disease has spread to distant sites beyond the axillary lymph nodes. There is no cure for metastatic breast cancer. There is no stage after IV.
It usually occurs several years after the primary breast cancer, although it is sometimes diagnosed at the same time as the primary breast cancer or, rarely, before the primary breast cancer has been diagnosed.
Metastatic breast cancer cells frequently differ from the preceding primary breast cancer in properties such as receptor status. The cells have often developed resistance to several lines of previous treatment and have acquired special properties that permit them to metastasize to distant sites. Metastatic breast cancer can be treated, sometimes for many years, but it cannot be cured. Distant metastases are the cause of about 90% of deaths due to breast cancer.
Breast cancer can metastasize anywhere in body but primarily metastasizes to the bone, lungs, regional lymph nodes, liver and brain, with the most common site being the bone. Treatment of metastatic breast cancer depends on location of the metastatic tumours and includes surgery, radiation, chemotherapy, biological, and hormonal therapy.
Typical environmental barriers in a metastatic event include physical (a basement membrane), chemical (reactive oxygen species or ROS, hypoxia and low pH) and biological (immune surveillance, inhibitory cytokines and regulatory extra-cellular matrix (ECM) peptides) components. Organ-specific anatomic considerations also influence metastasis; these include blood-flow patterns from the primary tumor and the homing ability of cancer cells to certain tissues. The targeting by cancer cells of specific organs is probably regulated by chemo-attractant factors and adhesion molecules produced by the target organ, along with cell-surface receptors expressed by the tumor cells.
Triple-negative breast cancers (TNBC) are sometimes classified into "basal-type" and other cancers; however, there is no standard classification scheme. Basal type cancers are frequently defined by cytokeratin 5/6 and EGFR staining. However, no clear criteria or cutoff values have been standardized yet. About 75% of basal-type breast cancers are triple negative.
Some TNBC overexpress epidermal growth factor receptor (EGFR) or transmembrane glycoprotein NMB (GPNMB).
Upon histologic examination, triple-negative breast tumors mostly fall into the categories of "secretory cell carcinoma" or "adenoid cystic types" (both considered less aggressive); "medullary cancers" and grade 3 invasive "ductal carcinomas" with no specific subtype; and highly aggressive "metastatic cancers". Medullary TNBC in younger women are frequently "BRCA1"-related.
Rare forms of triple-negative breast cancer are "apocrine" and "squamous carcinoma". "Inflammatory breast cancer" is also frequently triple negative.
Many proteins such as Caveolin 1/2, Survivin are researched as possible classification or prognostic factors.
TNBCs have been classified using an integrative analysis of cancer genomics data (DNA copy number, DNA methylation, and mRNA) and PPI data from a prognostic point of view and several key subnetworks (i.e. ubiquitin/proteasome, complement system, metabolism-related Warburg effect, ER-Golgi-cell surface trafficking, transcription) significantly related to patient survival have been identified.
Krukenberg tumors often come to the attention when they cause abdominal or pelvic pain, bloating, ascites, or pain during sexual intercourse. Krukenberg tumors can occasionally provoke a reaction of the ovarian stroma which leads to hormone production, that results in vaginal bleeding, a change in menstrual habits, or hirsutism, or occasionally virilization as a main symptom.
All these symptoms are non-specific and can also arise with a range of problems other than cancer, and a diagnosis can only be made following confirmatory investigations such as computed tomography (CT) scans, laparotomy and/or a biopsy of the ovary.
Initially, nearby lymph nodes are struck early. The lungs, liver, brain, and bones are the most common metastasis locations from solid tumors.
- In lymph nodes, a common symptom is lymphadenopathy
- Lungs: cough, hemoptysis and dyspnea (shortness of breath)
- Liver: hepatomegaly (enlarged liver), nausea and jaundice
- Bones: bone pain, fracture of affected bones
- Brain: neurological symptoms such as headaches, seizures, and vertigo
Although advanced cancer may cause pain, it is often not the first symptom.
Some patients, however, do not show any symptoms.
When the organ gets a metastatic disease it begins to shrink until its lymph nodes burst, or undergo lysis.
Sex cord–gonadal stromal tumour (or sex cord–stromal tumour) is a group of tumors derived from the stromal component of the ovary and testis, which comprises the granulosa, thecal cells and fibrocytes. In contrast, the epithelial cells originate from the outer epithelial lining surrounding the gonad while the germ cell tumors arise from the precursor cells of the gametes, hence the name germ cell. In humans, this group accounts for 8% of ovarian cancers and under 5% of testicular cancers. Their diagnosis is histological: only a biopsy of the tumour can make an exact diagnosis. They are often suspected of being malignant prior to operation, being solid ovarian tumours that tend to occur most commonly in post menopausal women.
This group of tumours is significantly less common than testicular germ cell tumours in men, and slightly less common than ovarian germ cell tumours in women (see Ovarian cancer).
Despite their name, germ cell tumors occur both within and outside the ovary and testis.
- head
- inside the cranium — pineal and suprasellar locations are most commonly reported
- inside the mouth — a fairly common location for teratoma
- neck
- mediastinum — account for 1% to 5% of all germ cell neoplasms
- pelvis, particularly sacrococcygeal teratoma
- ovary
- testis
In females, germ cell tumors account for 30% of ovarian tumors, but only 1 to 3% of ovarian cancers in North America. In younger women germ cell tumors are more common, thus in patients under the age of 21, 60% of ovarian tumors are of the germ cell type, and up to one-third are malignant. In males, germ cell tumors of the testis occur typically after puberty and are malignant (testicular cancer). In neonates, infants, and children younger than 4 years, the majority of germ cell tumors are sacrococcygeal teratomas.
Males with Klinefelter syndrome have a 50 times greater risk of germ cell tumors (GSTs). In these persons, GSTs usually contain nonseminomatous elements, present at an earlier age, and seldom are gonadal in location.
These tumours are of the following types, characterized by their abnormal production of otherwise apparently normal cells or tissues.
Although each of the cell and tissue types normally occurs in just one sex (male or female), within a tumour they can occur in the opposite sex. Consequently, depending on the specific histology produced, these tumours can cause virilization in women and feminization in men.
GCNIS is seen in the following settings:
- Almost all invasive germ cell tumours of the testis in adults
- Fifty percent of patients with GCNIS developed invasive germ cell tumours within five years of initial diagnosis.
- Five percent of contralateral testes in men with a history of prior testicular germ cell tumour.
- Less than five percent of cryptorchid testes.
- Less than one percent of patients with infertility.
Krukenberg tumors can be seen in all age groups, with an average age of 45 years. In most countries, cancer that has metastasized to the ovary accounts for only about 1 to 2% of ovarian cancer; in the remainder, the ovary itself is the primary cancer site. However, in Japan they represent a much higher percentage of malignancies in the ovary (almost 20%) due to the increased prevalence of gastric cancer.
Krukenberg tumors account for about 15% of metastatic cancers that initially appear to have arisen in the ovary, and as such is less common than metastasis arising from ovarian epithelial and germ-cell tumors.
In people who have had nongynecologic malignancy, approximately 20% of adnexal masses are malignant, and 60% of these are Krukenberg tumors.
Mixed germ cell tumors occur in many forms. Among these, a common form is teratoma with endodermal sinus tumor.
Teratocarcinoma refers to a germ cell tumor that is a mixture of teratoma with embryonal carcinoma, or with choriocarcinoma, or with both. This kind of mixed germ cell tumor may be known simply as a teratoma with elements of embryonal carcinoma or choriocarcinoma, or simply by ignoring the teratoma component and referring only to its malignant component: embryonal carcinoma and/or choriocarcinoma. They can present in the anterior mediastinum.
Signs and symptoms of TCC are entirely dependent on the location and extent of the cancer.
Most cancers typically present as a single primary tumor. Over the course of time—particularly if the primary tumor is left untreated—smaller "satellite" tumors will appear at other places in the body, a phenomenon known as metastasis. Less commonly, a metastatic tumor is found first; but in most such cases, the primary tumor can then be located via examination and testing. Rarely (3-5% of the time), the primary tumor cannot be found because it is too small, or because it has regressed due to immune system activity or other factors. In such situations a diagnosis of cancer of unknown primary origin (CUP) is made.
CUP usually comes to attention because of masses or swellings found somewhere in the body, either by physical examination or on medical imaging performed for another indication. The disease typically develops rapidly, and metastases may occur in places in the body that are otherwise unusual. Comprehensive physical examination is part of the process to identify a possible primary source of cancer; this should include the breasts, lymph nodes, the skin, external genitals, as well as an internal examination of the rectum and of the pelvic organs.
The location of metastases may be a clue as to the underlying source, even if this cannot be found on investigations. For instance, a woman in whom there is axillary lymphadenopathy (swelling in the lymph nodes of the armpit) it is likely that the cancer originated in the breast, and men with lymph node deposits in the mediastinum of the chest and/or retroperitoneal space of the abdomen may have a germ cell tumor.
Not all germ cell tumors (GCTs) arise from "intratubular germ cell neoplasia". The following testicular GCTs do not arise from ITGCN:
- Spermatocytic seminoma
- Pediatric Yolk sac tumors (endodermal sinus tumour). This is currently an area of controversy as some authors dispute the absence of ITGCN in these cases.
- Teratoma (rare exceptions)
Metastasis is a pathogenic agent's spread from an initial or primary site to a different or secondary site within the host's body; it is typically spoken of as such spread by a cancerous tumor. The newly pathological sites, then, are metastases (mets).
Cancer occurs after cells are genetically altered to proliferate rapidly and indefinitely. This uncontrolled proliferation by mitosis produces a primary heterogeneic tumour. The cells which constitute the tumor eventually undergo metaplasia, followed by anaplasia then dysplasia, resulting in a malignant phenotype. This malignancy allows for invasion into the circulation, followed by invasion to a second site for tumorigenesis.
Some cancer cells known as circulating tumor cells acquire the ability to penetrate the walls of lymphatic or blood vessels, after which they are able to circulate through the bloodstream to other sites and tissues in the body. This process is known (respectively) as "lymphatic" or "hematogenous" spread. After the tumor cells come to rest at another site, they re-penetrate the vessel or walls and continue to multiply, eventually forming another clinically detectable tumor. This new tumor is known as a metastatic (or "secondary") tumor. Metastasis is one of the hallmarks of cancer, distinguishing it from benign tumors. Most cancers can metastasize, although in varying degrees. Basal cell carcinoma for example rarely metastasizes.
When tumor cells metastasize, the new tumor is called a "secondary" or "metastatic" tumor, and its cells are similar to those in the original or primary tumor. This means that if breast cancer metastasizes to the lungs, the secondary tumor is made up of abnormal breast cells, not of abnormal lung cells. The tumor in the lung is then called "metastatic breast cancer", not "lung cancer". Metastasis is a key element in cancer staging systems such as the TNM staging system, where it represents the "M". In overall stage grouping, metastasis places a cancer in Stage IV. The possibilities of curative treatment are greatly reduced, or often entirely removed, when a cancer has metastasized.
Cancer of unknown primary origin (CUP, "occult cancer") is a cancer that is determined to be at the metastatic stage at the time of diagnosis, but a primary tumor cannot be identified. A diagnosis of CUP requires a clinical picture consistent with metastatic disease and one or more biopsy results inconsistent with a primary tumor.
CUP is found in about 3 to 5% of all people diagnosed with invasive cancer, and carries a poor prognosis in most (80 to 85%) of those circumstances. The other 15 to 20% of patients, however, have a relatively long survival with appropriate treatment.
Transitional cell carcinoma (TCC) also urothelial carcinoma (UCC), is a type of cancer that typically occurs in the urinary system. It is the most common type of bladder cancer and cancer of the ureter, urethra, and urachus. It is the second most common type of kidney cancer, but accounts for only five to 10 percent of all primary renal malignant tumors.
TCC arises from the transitional epithelium, a tissue lining the inner surface of these hollow organs.
When the term "urothelial" is used, it specifically refers to a carcinoma of the urothelium, meaning a TCC of the urinary system.
Choriocarcinoma is a malignant, trophoblastic cancer, usually of the placenta. It is characterized by "early hematogenous spread" to the lungs. It belongs to the malignant end of the spectrum in gestational trophoblastic disease (GTD). It is also classified as a germ cell tumor and may arise in the testis or ovary.
A urogenital neoplasm is a tumor of the urogenital system.
Types include:
- Cancer of the breast and female genital organs: (Breast cancer, Vulvar cancer, Vaginal cancer, Cervical cancer, Uterine cancer, Endometrial cancer, Ovarian cancer)
- Cancer of the male genital organs (Carcinoma of the penis, Prostate cancer, Testicular cancer)
- Cancer of the urinary organs (Renal cell carcinoma, Bladder cancer)
Unlike benign germ cell tumors of the mediastinum, malignant mediastinal tumors are usually symptomatic at the time of diagnosis. Most mediastinal malignant tumors are large and cause symptoms by compressing or invading adjacent structures, including the lungs, pleura, pericardium, and chest wall.
Seminomas grow relatively slowly and can become very large before causing symptoms. Tumors 20 to 30 cm in diameter can exist with minimal symptomatology.