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The definitive diagnosis is by histologic analysis, i.e. and examination under the microscope.
Under the microscope, OKCs vaguely resemble keratinized squamous epithelium; however, they lack rete ridges and often have an artifactual separation from their basement membrane.
On a CT scan, The radiodensity of a keratocystic odontogenic tumour is about 30 Hounsfield units, which is about the same as ameloblastomas. Yet, ameloblastomas show more bone expansion and seldom show high density areas.
Radiologically
- Odontogenic Myxoma
- Ameloblastoma
- Central Giant Cell Granuloma
- Adenomatoid odontogenic tumor
Histologically
- Orthokeratocyst
- Radicular cyst (particularly if the OKC is very inflamed)
- Unicystic ameloblastoma
Although often described as benign, a teratoma does have malignant potential. In a UK study of 351 infants and children diagnosed with "benign" teratoma reported 227 with MT, 124 with IT. Five years after surgery, event-free survival was 92.2% and 85.9%, respectively, and overall survival was 99% and 95.1%. A similar study in Italy reported on 183 infants and children diagnosed with teratoma. At 10 years after surgery, event free and overall survival were 90.4% and 98%, respectively.
Depending on which tissue(s) it contains, a teratoma may secrete a variety of chemicals with systemic effects. Some teratomas secrete the "pregnancy hormone" human chorionic gonadotropin (βhCG), which can be used in clinical practice to monitor the successful treatment or relapse in patients with a known HCG-secreting teratoma. This hormone is not recommended as a diagnostic marker, because most teratomas do not secrete it. Some teratomas secrete thyroxine, in some cases to such a degree that it can lead to clinical hyperthyroidism in the patient. Of special concern is the secretion of alpha-fetoprotein (AFP); under some circumstances AFP can be used as a diagnostic marker specific for the presence of yolk sac cells within the teratoma. These cells can develop into a frankly malignant tumor known as yolk sac tumor or endodermal sinus tumor.
Adequate follow-up requires close observation, involving repeated physical examination, scanning (ultrasound, MRI, or CT), and measurement of AFP and/or βhCG.
Extraspinal ependymoma, usually considered to be a glioma (a type of non-germ cell tumor), may be an unusual form of mature teratoma.
GCNIS is not palpable, and not visible on macroscopic examination of testicular tissue. Microscopic examination of affected testicular tissue most commonly shows germ cells with enlarged hyperchromatic nuclei with prominent nucleoli and clear cytoplasm. These cells are typically arranged along the basement membrane of the tubule, and mitotic figures are frequently seen. The sertoli cells are pushed toward the lumen by the neoplastic germ cells, and spermatogenesis is almost always absent in the affected tubules. Pagetoid spread of GCNIS into the rete testis is common. Immunostaining with placental alkaline phosphatase (PLAP) highlights GCNIS cell membranes in 95 percent of cases. OCT3/4 is a sensitive and specific nuclear stain of GCNIS.
Treatment is by excisional biopsy, wide local excision and possibly sentinel node biopsy. Spread of disease to local lymph nodes or distant sites (typically brain, bone, skin and lung) marks a decidedly poor prognosis.
GCNIS is generally treated by radiation therapy and/or orchiectomy. Chemotherapy used for metastatic germ cell tumours may also eradicate GCNIS.
Heck's disease (also known as focal or multifocal epithelial hyperplasia) is an asymptomatic, benign neoplastic condition characterized by multiple white to pinkish papules that occur diffusely in the oral cavity. Can present with slightly pale, smooth or roughened surface morphology. It is caused by the human papilloma virus types 13 and 32. It exhibits surface cells with vacuolated cytoplasm around irregular, pyknotic nuclei and occasional cells with mitosis-like changes within otherwise mature and well-differentiated epithelium. A distinguishing histologic feature is elongated rete ridges resembling Bronze Age axe with mitosoid bodies present. It was first identified in the Aboriginal population.
Over time, they will spontaneously regress without treatment. Possible treatment may be excisional biopsy for lesions of functional or aesthetic concern.
The diagnosis is made clinically, and usually this is clear cut if the lesion is associated with the flange of a denture. Tissue biopsy is not usually indicated before removal of the lesion, since the excises surgical specimen is usually sent for histopathologic examination and the diagnosis is confirmed retrospectively. Rarely, incisional biopsy may be indicated to rule out neoplasia, e.g. in the presence of suspicious ulceration. The appearance may also be confused with pyogenic granuloma.
The excessive tissue is composed of cellular, inflamed fibrous connective tissue. The appearance of an epulis fissuratum microscopically is an overgrowth of cells from the fibrous connective tissue. The epithelial cells are usually hyperkeratotic and irregular, hyperplastic rete ridges are often seen.
Tissue biopsy is usually indicated to rule out other causes of white patches and also to enable a detailed histologic examination to grade the presence of any epithelial dysplasia. This is an indicator of malignant potential and usually determines the management and recall interval. The sites of a leukoplakia lesion that are preferentially biopsied are the areas that show induration (hardening) and erythroplasia (redness), and erosive or ulcerated areas. These areas are more likely to show any dysplasia than homogenous white areas.
Brush biopsy/exfoliative cytology is an alternative to incisional biopsy, where a stiff brush is scraped against the lining of the mouth to remove a sample of cells. This is then made into a smear which can be examined microscopically. Sometimes the biopsy site can be selected with adjunct methods which aim to highlight areas of dysplasia. Toluidine blue staining, where the dye is preferentially retained by dysplastic tissue, is sometimes used, but there is high false positive rate. Other methods involve the use of illuminescence, relying on either the property of normal autoflorescent molecules in mucosa such as collagen and keratin which is lost from areas of dysplasia or carcinoma under blue light, or by initially staining of the mucosa with toluidine blue or dilute acetic acid and examination under white light.
Spermatoceles can be discovered as incidental scrotal masses found on physical examination by a physician. They may also be discovered by self-inspection of the scrotum and testicles.
Finding a painless, cystic mass at the head of the epididymis, that transilluminates and can be clearly differentiated from the testicle, is generally sufficient. If uncertainty exists, ultrasonography of the scrotum can confirm if it is spermatocele.
If an individual finds what he suspects to be a spermatocele, he is advised to consult a urologist.
A struma ovarii (literally: goitre of the ovary) is a rare form of monodermal teratoma that contains mostly thyroid tissue, which may cause hyperthyroidism.
Despite its name, struma ovarii is not restricted to the ovary.
The vast majority of struma ovarii are benign tumors; however, malignant tumors of this type is found in a small percentage of cases.
There is no simple and reliable way to test for ovarian cancer in women who do not have any signs or symptoms. The Pap test does not screen for ovarian cancer.
Screening is not recommended in women who are at average risk, as evidence does not support a reduction in death and the high rate of false positive tests may lead to unneeded surgery, which is accompanied by its own risks.
Ovarian cancer is usually only palpable in advanced stages. Screening is not recommended using CA-125 measurements, HE4 levels, ultrasound, or adnexal palpation in women who are at average risk. Risk of developing ovarian cancer in those with genetic factors can be reduced. Those with a genetic predisposition may benefit from screening. This high risk group has benefited with earlier detection.
Ovarian cancer has low prevalence, even in the high-risk group of women from the ages of 50 to 60 (about one in 2000), and screening of women with average risk is more likely to give ambiguous results than detect a problem which requires treatment. Because ambiguous results are more likely than detection of a treatable problem, and because the usual response to ambiguous results is invasive interventions, in women of average risk, the potential harms of having screening without an indication outweigh the potential benefits. The purpose of screening is to diagnose ovarian cancer at an early stage, when it is more likely to be treated successfully.
Screening with transvaginal ultrasound, pelvic examination, and CA-125 levels can be used instead of preventative surgery in women who have BRCA1 or BRCA2 mutations. This strategy has shown some success.
The ultrasound (US) features of struma ovarii are nonspecific, but a heterogeneous, predominantly solid mass may be seen. US demonstrates a complex appearance with multiple cystic and solid areas, findings that reflect the gross pathologic appearance of the tumor.
Magnetic resonance imaging findings may be more characteristic: The cystic spaces demonstrate both high and low signal intensity on T1- and T2-weighted images. Some of the cystic spaces may demonstrate low signal intensity on both T1- and T2-weighted images due to the thick, gelatinous colloid of the struma. No fat is evident in these lesions.
If the causative factor persists, tissue will become more fibrous over time.
Gardasil 6 is an HPV vaccine aimed at preventing cervical cancers and genital warts. Gardasil is designed to prevent infection with HPV types 16, 18, 6, and 11. HPV types 16 and 18 currently cause about 70% of cervical cancer cases, and also cause some vulvar, vaginal, penile and anal cancers. HPV types 6 and 11 are responsible for 90% of documented cases of genital warts.
Gardasil 9, approved in 2014 protects against HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58.
HPV vaccines do not currently protect against the virus strains responsible for plantar warts (verrucas).
Leukoplakia has a wide range of possible histologic appearances. The degree of hyperkeratosis, epithelial thickness (acanthosis/), dysplasia and inflammatory cell infiltration in the underlying lamina propria are variable. In mucous membranes, hyperkeratosis can be defined as "an increase in the thickness of the keratin layer of the epithelium, or the presence of such a layer in a site where none would normally be expected." In leukoplakia, the hyperkeratosis varies in thickness, and may be either ortho- or para-keratosis, (depending upon whether cell nuclei are lost or retained in the superficial layers respectively), or a mixture of both in different areas of the lesion.
The epithelium may show hypertrophy (e.g. acanthosis) or atrophy. Red areas within leukoplakia represent atrophic or immature epithelium which has lost the ability to keratinize. The transition between the lesion and normal surrounding mucosa may be well demarcated, or poorly defined. Melanin, a pigment naturally produced in oral mucosa, can leak from cells and give a grey color to some leukoplakia lesions.
Hyperkeratosis and altered epithelial thickness may be the only histologic features of a leukoplakia lesion, but some show dysplasia. The word "dysplasia" generally means "abnormal growth", and specifically in the context of oral red or white lesions refers to microscopic changes ("cellular atypia") in the mucosa that indicate a risk of malignant transformation. When dysplasia is present, there is generally an inflammatory cell infiltration in the lamina propria. The following are commonly cited as being possible features of epithelial dysplasia in leukoplakia specimens:
- Cellular pleomorphism, in which cells are of abnormal and different shapes.
- Nuclear atypia, in which the nuclei of cells varies in size, any may be increased in size relative to the cytoplasm, shape, and may stain more intensely. There may also be more prominent nucleoli.
- Increased number of cells seen undergoing mitosis, including both normal and abnormal mitoses. Abnormal mitosis may be abnormally located, e.g. occurring in suprabasal cells (cell layers more superficial to the basal cell layer) or of abnormal form, e.g. "tri-radiate mitoses" (a cell splitting into 3 daughter cells rather than only 2)
- Loss the normal organization of the epithelial layers. The distinction between the epithelial layers may be lost. Normally stratified squamous epithelium shows progressive changes in the form of cells from the basal to the superficial layers, with cells becoming more flat ("squames") towards the surface as a continuous maturation process. In dysplastic epithelium, cells may become vertically orientated rather than becoming flat towards the surface.
- There may be abnormal keratinization, where keratin is formed below the normal keratin layer. This can occur in individual cells or groups of cells, forming an intraepithelial keratin pearl. There may be an increase in number of basal cells, and they may lose their cellular orientation (losing their polarity and long axis).
- Alteration of the normal epithelial-connective tissue architecture - the rete pegs may become "drop shaped". wider at their base than more superficially.
Generally dysplasia is subjectively graded by pathologists into mild, moderate or severe dysplasia. This requires experience as it is a difficult skill to learn. It has been shown that there is high degree of inter-observer variation and poor reproducibility in how dysplasia is graded. Severe dysplasia is synonymous with the term carcinoma in situ, denoting the presence of neoplastic cells which have not yet penetrated the basement membrane and invaded other tissues.
Leukoedema is a harmless condition, and no treatment is indicated. People may be alarmed by the appearance and benefit from reassurance.
Small cysts are best left alone, as are larger cysts that are an asymptomatic condition. Only when the cysts are causing discomfort and are enlarging in size, or the patient wants the spermatocele removed, should a spermatocelectomy be considered. Pain may persist even after removal.
Spermatocelectomy can be performed on an outpatient basis, with the use of local or general anesthesia.
A spermatocelectomy will not improve fertility.
Superficial spreading melanoma (also known as "superficially spreading melanoma") (SSM) is usually characterized as the most common form of cutaneous melanoma in Caucasians. The average age at diagnosis is in the fifth decade, and it tends to occur on sun-exposed skin, especially on the backs of males and lower limbs of females.
The diagnosis is usually made on the clinical appearance, and tissue biopsy is not usually needed. The histologic picture is one of superficial candidal hyphal infiltration and a polymorphonuclear leukocytic inflammatory infiltrate present in the epithelium. The rete ridges are elongated and hyperplastic (pseudoepitheliomatous hyperplasia, which may be mistaken for carcinoma).
People with strong genetic risk for ovarian cancer may consider the surgical removal of their ovaries as a preventative measure. This is often done after completion of childbearing years. This reduces the chances of developing both breast cancer (by around 50%) and ovarian cancer (by about 96%) in people at high risk. Women with "BRCA" gene mutations usually also have their Fallopian tubes removed at the same time (salpingo-oophorectomy), since they also have an increased risk of Fallopian tube cancer. However, these statistics may overestimate the risk reduction because of how they have been studied.
People with a significant family history for ovarian cancer are often referred to a genetic counselor to see if they if testing for BRCA mutations would be beneficial. The use of oral contraceptives, the absence of 'periods' during the menstrual cycle, and tubal ligation reduce the risk.
There may an association of developing ovarian cancer and ovarian stimulation during infertility treatments. Endometriosis has been linked to ovarian cancers. Human papillomavirus infection, smoking, and talc have not been identified as increasing the risk for developing ovarian cancer.
Common warts have a characteristic appearance under the microscope. They have thickening of the stratum corneum (hyperkeratosis), thickening of the stratum spinosum (acanthosis), thickening of the stratum granulosum, rete ridge elongation, and large blood vessels at the dermoepidermal junction.
After removal, the testicle is fixed with Bouin's solution because it better conserves some morphological details such as nuclear conformation. Then the testicular tumor is staged by a pathologist according to the TNM Classification of Malignant Tumors as published in the AJCC Cancer Staging Manual. Testicular cancer is categorized as being in one of three stages (which have subclassifications). The size of the tumor in the testis is irrelevant to staging. In broad terms, testicular cancer is staged as follows:
- Stage I: the cancer remains localized to the testis.
- Stage II: the cancer involves the testis and metastasis to retroperitoneal and/or paraaortic lymph nodes (lymph nodes below the diaphragm).
- Stage III: the cancer involves the testis and metastasis beyond the retroperitoneal and paraaortic lymph nodes. Stage 3 is further subdivided into non-bulky stage 3 and bulky stage 3.
Further information on the detailed staging system is available on the website of the American Cancer Society.
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