Immature teratoma | |
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Micrograph of the primitive neuroepithelium of an immature teratoma. H&E stain. | |
Specialty | Oncology |
An immature teratoma is a teratoma that contains anaplastic immature elements, and is often synonymous with malignant teratoma. [1] A teratoma is a tumor of germ cell origin, containing tissues from more than one germ cell line, [2] [3] [4] It can be ovarian or testicular in its origin. [4] and are almost always benign. [5] An immature teratoma is thus a very rare tumor, representing 1% of all teratomas, 1% of all ovarian cancers, and 35.6% of malignant ovarian germ cell tumors. [6] It displays a specific age of incidence, occurring most frequently in the first two decades of life and almost never after menopause. [4] Unlike a mature cystic teratoma, an immature teratoma contains immature or embryonic structures. It can coexist with mature cystic teratomas and can constitute of a combination of both adult and embryonic tissue. [7] [8] The most common symptoms noted are abdominal distension and masses. [9] Prognosis and treatment options vary and largely depend on grade, stage and karyotype of the tumor itself.
At CT and MRI, an immature teratoma possesses characteristic appearance. It is typically large (12–25 cm) and has prominent solid components with cystic elements. [10] It is usually filled with lipid constituents and therefore demonstrates fat density at CT and MRI. [10] Ultrasound appearance of an immature teratoma is nonspecific. It is highly heterogeneous with partially solid lesions and scattered calcifications. [11] [12]
Traditionally, comprehensive surgical staging is performed via exploratory laparotomy with cytologic washings, peritoneal biopsies, an omental assessment (either biopsy or rarely a full omentectomy), and both pelvic and aortic lymph node dissection. Laproscopy is often suggested as an alternative to surgically stage patients with immature teratoma. [13] [14]
Ovarian cancer is staged using the FIGO staging system and uses information obtained after surgery, which can include a total abdominal hysterectomy via midline laparotomy, unilateral (or bilateral) salpingo-oophorectomy, pelvic (peritoneal) washings, assessment of retroperitoneal lymph nodes and/or appendectomy. [15] [16] The AJCC staging system, identical to the FIGO staging system, describes the extent of tumor (T), the presence of absences of metastases to lymph nodes (N), the presence or absence of distant metastases (M). [17]
Stage | Description | |||
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I | Cancer is completely limited to the ovary | |||
IA | involves one ovary, capsule intact, no tumor on ovarian surface, negative washings | |||
IB | involves both ovaries; capsule intact; no tumor on ovarian surface; negative washings | |||
IC | tumor involves one or both ovaries | |||
IC1 | surgical spill | |||
IC2 | capsule has ruptured or tumor on ovarian surface | |||
IC3 | positive ascites or washings | |||
II | pelvic extension of the tumor (must be confined to the pelvis) or primary peritoneal tumor, involves one or both ovaries | |||
IIA | tumor found on uterus or fallopian tubes | |||
IIB | tumor elsewhere in the pelvis | |||
III | cancer found outside the pelvis or in the retroperitoneal lymph nodes, involves one or both ovaries | |||
IIIA | metastasis in retroperitoneal lymph nodes or microscopic extrapelvic metastasis | |||
IIIA1 | metastasis in retroperitoneal lymph nodes | |||
IIIA1(i) | the metastasis is less than 10 mm in diameter | |||
IIIA1(ii) | the metastasis is greater than 10 mm in diameter | |||
IIIA2 | microscopic metastasis in the peritoneum, regardless of retroperitoneal lymph node status | |||
IIIB | metastasis in the peritoneum less than or equal to 2 cm in diameter, regardless of retroperitoneal lymph node status; or metastasis to liver or spleen capsule | |||
IIIC | metastasis in the peritoneum greater than 2 cm in diameter, regardless of retroperitoneal lymph node status; or metastasis to liver or spleen capsule | |||
IV | distant metastasis (i.e. outside of the peritoneum) | |||
IVA | pleural effusion containing cancer cells | |||
IVB | metastasis to distant organs (including the parenchyma of the spleen or liver), or metastasis to the inguinal and extra-abdominal lymph nodes |
An immature teratoma contains varying compositions of adult and embryonic tissue. The most common embryonic component identified in immature teratomas is the neuroectoderm. [19] Occasionally, tumors may present neuroepithelium that resemble neuroblasts. [19] Tumors may also present embryonic components such as immature cartilage and skeletal muscle of mesodermal origin. [19] Immature teratomas composed of embryonic endodermal derivatives are rare. [19]
Often a mature cystic teratoma is misdiagnosed as its immature counterpart due to the misinterpretation of mature neural tissue as immature. [20] While mature neural cells have nuclei with uniformly dense chromatin and neither exhibit apoptotic or mitotic activity, immature neural cells have nuclei with vesicular chromatin and exhibit both apoptotic and mitotic activity. [20] A recent study has identified the use of Oct-4 as a reliable biomarker for the diagnosis of highly malignant cases of immature teratomas. [21]
Thurlbeck and Scully devised a grading system for “pure” immature teratomas on the basis of differentiation of the cellular elements of the tumor. [22] The proportion of immature tissue elements defines the grade of immaturity. [22] This was later modified by Norris et al. (1976), who added a quantitative aspect to the degree of immaturity. [23]
Grade | Thurlbeck and Scully (1960) | Norris et al. (1976) |
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0 | All cells are well differentiated | All cells are mature; mitotic activity is rare or absent. |
1 | Cells are well differentiated except in rare small foci of embryonic tissue; neuroepithelium is absent or rare | Neuroepithelium absent or limited to fewer than one low-magnification field (x40) per slide |
2 | Moderate quantities of embryonic tissue present; cells show atypicality and mitotic activity | Neuroepithelium does not exceed more than three low-magnification fields (x40) per slide |
3 | Large quantities of embryonic tissue present; cells show atypicality and mitotic activity | Neuroepithelium exceeds more than three low-magnification fields (x40) per slide |
An ovarian immature teratoma is karyotypically normal 46,XX or near-normal. Grade 1 or 2 tumors exhibit 46,XX normal karyotype, whereas grade 3 tumors show a variety of abnormal karyotypes. [24] Though immature teratoma cells show a normal karyotype, there may still be detectable alterations in the gene level and that these aberrations may influence the stability of chromosome status. [24]
Ovarian immature teratomas have been classified as among the least mutated of all solid cancers. [25] Immature teratomas originate from germ cells that undergo one of several meiotic failures, leading to a tumor genome with high levels of copy neutral loss of heterozygosity. [25]
Though several studies have shown that size and stage of the primary tumor are related to survival, the grade of the tumor is the best determinant of prognosis prior to peritoneal spread. [23] [24] Once peritoneal spread has occurred, the grade of metastatic lesions or implants is the best determinant of prognosis. [23] [24] Multiple sections of the primary tumor and wide sampling of the implants are necessary to properly grade the tumor. In most cases, the implants are better differentiated than the primary tumors. [8] Gliomatosis peritonei, a rare condition often associated with immature ovarian teratoma, is characterized by the presence of mature glial implants in the peritoneum. [26] Yoon et al. (2012), reported that immature ovarian teratoma patients with Gliomatosis peritonei have larger tumors, more frequent recurrence and higher CA-125 levels than immature ovarian teratoma patients without gliomatosis peritonei. [27]
A high degree of immaturity in the primary tumor, one that corresponds with a grade 3 diagnosis is a sign of poor prognosis. [23] [8] [28] [29] Grade 3 tumors often display chromosomal abnormalities, also an indication of poor prognosis. [24] Tumor grade is the most important factor for relapse in immature teratomas. [28] Vicus et al. (2011), reported that grade 2 or 3 tumors are associated with a greater chance of relapse that can be fatal, predominantly within 2 years of diagnosis. [30] Among grade 3 patients, the stage was significantly associated with relapse. [30]
In the past, survival rates were low for high-grade immature teratomas. Norris et al. (1976), reported a survival rate of 82% for patients with grade 1 tumors, 62% for grade 2 and 30% for grade 3 tumors. [23] However, these results antedate the use of multi-agent chemotherapy. [8] With the advent of multiagent chemotherapy after surgical resection, long-term remission and increased survival rates have been achieved. Pashankar et al. (2016), reported that the estimated 5-year overall survival rate for grade 3 Stage I and II disease was 91% compared with 88% for grade 3, Stage III and IV disease. [28]
Histologic grade and fertility desires of the patient are key considerations in determining treatment options. In adult women postoperative adjuvant chemotherapy is standard except for stage I /grade 1 disease. In pediatric patients, surgery alone is standard. [28]
Since the occurrence of immature teratoma is very rarely bilateral, current standard of care of unilateral salpingo-oophorectomy with wide sampling of peritoneal implants. [8] Total abdominal hysterectomy with bilateral salpingo-oophorectomy are not indicated as they do not influence outcomes. [8] Fertility-sparing surgery in the form of unilateral salpingo-oophorectomy is the primary treatment modality in young patients. [31] [32] [33] Some physicians recommend ovarian cystectomy alone, rather than a unilateral salpingo-oophorectomy for patients with an early stage low grade disease. Zhao et al. (2017), reported no significant differences in survival rates or post-operative fertility outcomes between the two treatment options. [34] However, others caution against such an approach. [8]
Norris et al. (1976) observed an 18% recurrence rate in grade 2 tumors and 70% recurrence in grade 3 tumors. [23] Gershenson et al. (1986), reported outcomes of 41 patients with Stage I-IV disease and observed recurrences in 94% of patients treated with surgery alone compared with 14% in patients treated with surgery and chemotherapy. [35] Studies like these resulted in the recommendation to use chemotherapy for grade 2 and 3 tumors. Currently, the use of multi agent chemotherapy for adult patients with ovarian immature teratoma is standard of care except for grade 1, stage I tumors. [28] There is considerable experience with a combination of vincristine, dactinomycin, and cyclophosphamide (VAC) given in an adjuvant setting; however, combinations containing cisplatin, etoposide, and bleomycin (BEP) are now preferred because of a lower relapse rate and shorter treatment time. [36] While a prospective comparison of VAC versus BEP has not been performed, in well-staged patients with completely resected tumors, relapse is essentially unheard of following platinum-based chemotherapy. [36] However, the disease will recur in about 25% of well-staged patients treated with 6 months of VAC. [37]
A teratoma is a tumor made up of several different types of tissue, such as hair, muscle, teeth, or bone. Teratomata typically form in the tailbone, ovary, or testicle.
Ovarian cancer is a cancerous tumor of an ovary. It may originate from the ovary itself or more commonly from communicating nearby structures such as fallopian tubes or the inner lining of the abdomen. The ovary is made up of three different cell types including epithelial cells, germ cells, and stromal cells. When these cells become abnormal, they have the ability to divide and form tumors. These cells can also invade or spread to other parts of the body. When this process begins, there may be no or only vague symptoms. Symptoms become more noticeable as the cancer progresses. These symptoms may include bloating, vaginal bleeding, pelvic pain, abdominal swelling, constipation, and loss of appetite, among others. Common areas to which the cancer may spread include the lining of the abdomen, lymph nodes, lungs, and liver.
A serous tumour is a neoplasm that typically has papillary to solid formations of tumor cells with crowded nuclei, and which typically arises on the modified Mullerian-derived serous membranes that surround the ovaries in females. Such ovarian tumors are part of the surface epithelial-stromal tumour group of ovarian tumors. They are common neoplasms with a strong tendency to occur bilaterally, and they account for approximately a quarter of all ovarian tumors.
Surface epithelial-stromal tumors are a class of ovarian neoplasms that may be benign or malignant. Neoplasms in this group are thought to be derived from the ovarian surface epithelium or from ectopic endometrial or Fallopian tube (tubal) tissue. Tumors of this type are also called ovarian adenocarcinoma. This group of tumors accounts for 90% to 95% of all cases of ovarian cancer; however is mainly only found in postmenopausal women with the exception of the United States where 7% of cases occur in women under the age of 40. Serum CA-125 is often elevated but is only 50% accurate so it is not a useful tumor marker to assess the progress of treatment. 75% of women with epithelial ovarian cancer are found within the advanced-stages; however younger patients are more likely to have better prognoses than older patients.
Granulosa cell tumours are tumours that arise from granulosa cells. They are estrogen secreting tumours and present as large, complex, ovarian masses. These tumours are part of the sex cord–gonadal stromal tumour or non-epithelial group of tumours. Although granulosa cells normally occur only in the ovary, granulosa cell tumours occur in both ovaries and testicles. These tumours should be considered malignant and treated in the same way as other malignant tumours of ovary. The ovarian disease has two forms, juvenile and adult, both characterized by indolent growth, and therefore has high recovery rates. The staging system for these tumours is the same as for epithelial tumours and most present as stage I. The peak age at which they occur is 50–55 years, but they may occur at any age.
Sex cord–gonadal 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.
Germ cell tumor (GCT) is a neoplasm derived from germ cells. Germ-cell tumors can be cancerous or benign. Germ cells normally occur inside the gonads. GCTs that originate outside the gonads may be birth defects resulting from errors during development of the embryo.
Pseudomyxoma peritonei (PMP) is a clinical condition caused by cancerous cells that produce abundant mucin or gelatinous ascites. The tumors cause fibrosis of tissues and impede digestion or organ function, and if left untreated, the tumors and mucin they produce will fill the abdominal cavity. This will result in compression of organs and will destroy the function of the colon, small intestine, stomach, or other organs. Prognosis with treatment in many cases is optimistic, but the disease is lethal if untreated, with death occurring via cachexia, bowel obstruction, or other types of complications.
In medicine, Meigs's syndrome, also Meigs syndrome or Demons–Meigs syndrome, is the triad of ascites, pleural effusion, and benign ovarian tumor. Meigs syndrome resolves after the resection of the tumor. Because the transdiaphragmatic lymphatic channels are larger in diameter on the right, the pleural effusion is classically on the right side. The causes of the ascites and pleural effusion are poorly understood. Atypical Meigs syndrome, characterized by a benign pelvic mass with right-sided pleural effusion but without ascites, can also occur. As in typical Meigs syndrome, pleural effusion resolves after removal of the pelvic mass.
A germinoma is a type of germ-cell tumor, which is not differentiated upon examination. It may be benign or malignant.
Ovarian tumors, or ovarian neoplasms, are tumors arising from the ovary. They can be benign or malignant. They consist of mainly solid tissue, while ovarian cysts contain fluid.
A gonadoblastoma is a complex neoplasm composed of a mixture of gonadal elements, such as large primordial germ cells, immature Sertoli cells or granulosa cells of the sex cord, and gonadal stromal cells. Gonadoblastomas are by definition benign, but more than 50% have a co-existing dysgerminoma which is malignant, and an additional 10% have other more aggressive malignancies, and as such are often treated as malignant.
Uterine clear-cell carcinoma (CC) is a rare form of endometrial cancer with distinct morphological features on pathology; it is aggressive and has high recurrence rate. Like uterine papillary serous carcinoma CC does not develop from endometrial hyperplasia and is not hormone sensitive, rather it arises from an atrophic endometrium. Such lesions belong to the type II endometrial cancers.
A borderline tumor, sometimes called low malignant potential (LMP) tumor, is a distinct but yet heterogeneous group of tumors defined by their histopathology as atypical epithelial proliferation without stromal invasion. It generally refers to such tumors in the ovary but borderline tumors may rarely occur at other locations as well.
Endodermal sinus tumor (EST) is a member of the germ cell tumor group of cancers. It is the most common testicular tumor in children under three, and is also known as infantile embryonal carcinoma. This age group has a very good prognosis. In contrast to the pure form typical of infants, adult endodermal sinus tumors are often found in combination with other kinds of germ cell tumor, particularly teratoma and embryonal carcinoma. While pure teratoma is usually benign, endodermal sinus tumor is malignant.
The ovarian fibroma, also fibroma, is a benign sex cord-stromal tumour.
Hyperthermic intrathoracic chemotherapy (HITOC) is part of a surgical strategy employed in the treatment of various pleural malignancies. The pleura in this situation could be considered to include the surface linings of the chest wall, lungs, mediastinum, and diaphragm. HITOC is the chest counterpart of HIPEC. Traditionally used in the treatment of malignant mesothelioma, a primary malignancy of the pleura, this modality has recently been evaluated in the treatment of secondary pleural malignancies.
High-grade serous carcinoma (HGSC) is a type of tumour that arises from the serous epithelial layer in the abdominopelvic cavity and is mainly found in the ovary. HGSCs make up the majority of ovarian cancer cases and have the lowest survival rates. HGSC is distinct from low-grade serous carcinoma (LGSC) which arises from ovarian tissue, is less aggressive and is present in stage I ovarian cancer where tumours are localised to the ovary.
An extracranial germ cell tumor (EGCT) occurs in the abnormal growth of germ cells in the gonads and the areas other than the brain via tissue, lymphatic system, or circulatory system. The tumor can be benign or malignant (cancerous) by its growth rate. According to the National Cancer Institute and St. Jude Children's Research Hospital, the chance of children who are under 15 years old having EGCTs is 3%, in comparison to adolescents, a possibility of 14% with aged 15 to 19 can have EGCTs. There is no obvious cut point in between children and adolescents. However, common cut points in researches are 11 years old and 15 years old.
Ovarian germ cell tumors (OGCTs) are heterogeneous tumors that are derived from the primitive germ cells of the embryonic gonad, which accounts for about 2.6% of all ovarian malignancies. There are four main types of OGCTs, namely dysgerminomas, yolk sac tumor, teratoma, and choriocarcinoma.
This article incorporates public domain material from Dictionary of Cancer Terms. U.S. National Cancer Institute.