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Description : Check out this medical presentation on Germ Cell Tumor, which is titled "Testis", to know about testicular tumor, tumor markers in diagnosis, morphology of seminoma, embryonal carcinoma and Yolk sac tumor, and cryptorchidism.

Tags : Germ Cell Tumor, Testis, testicular tumor, tumor markers, diagnosis, morphology, seminoma, embryonal carcinoma, Yolk sac tumor, cryptorchidism

Published on : May 18, 2021 | Views : 3961 | Downloads : 9

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Testis
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Must know 1-Classification of testicular tumor 2-Tumor markers in diagnosis 3-Morphology of Seminoma Embryonal carcinoma Yolk sac tumor 4-Cryptorchidism
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Testicular lesion Congenital Anomalies Regressive Changes Inflammation (Nonspecific , Specific Inflammations, Granulomatous (Autoimmune) Orchitis) Vascular Disorders(torsion) Spermatic Cord and Paratesticular Tumors Testicular Tumors
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INFLAMMATIONS- Inflammation of the testis is termed as orchitis and of epididymis is called as epididymitis; the latter being more common
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1-Non-specific Epididymitis and Orchitis- may be acute or chronic common routes of spread are via the vas deferens, or lymphatic and haematogenous routes caused by urethritis, cystitis, prostatitis and seminal vesiculitis common infecting organisms in Neisseria gonorrhoeae and Chlamydia trachomatis
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Grossly, acute stage- firm, tense, swollen and congested may be multiple abscesses, especially in gonorrhoeal infection chronic stage- variable degree of atrophy and fibrosis
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Histologically, acute- congestion, oedema and diffuse infiltration by neutrophils, or formation of neutrophilic abscesses Chronic- focal or diffuse chronic inflammation, disappearance of seminiferous tubules, fibrous scarring and destruction of interstitial Leydig cells
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2-Granulomatous (Autoimmune) Orchitis - Non-tuberculous granulomatous orchitis- unilateral, painless testicular enlargement may resemble a testicular tumour clinically autoimmune basis is suspected
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Gross- enlarged Cut section of the testicle is greyish-white to tan-brown Histologically, granulomatous reaction(non caseating) is present diffusely throughout the testis and is confined to the seminiferous tubules Peritubular fibrosis interstitial lymphocytes and plasma cells
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3-Tuberculous Epididymo-orchitis- invariably begins in the epididymis and spreads to the testis May spread via -tuberculous seminal vesiculitis, prostatitis and renal tuberculosis haematogenous spread- from tuberculosis of the lungs
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Grossly, discrete, yellowish, caseous necrotic areas Microscopically, numerous tubercles which may coalesce to form large caseous mass Characteristics of typical tubercles such as epithelioid cells, peripheral mantle of lymphocytes, occasional multinucleate giant cells and central areas of caseation necrosis are seen AFB positive
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4-Spermatic Granuloma(epididymitis nodosa) Spermatic granuloma is the term used for development of inflammatory lesions due to invasion of spermatozoa into the stroma
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MORPHOLOGIC FEATURES- Grossly, a small nodule, 3 mm to 3 cm in diameter in head of epididymis firm, white to yellowish-brown
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Histologically, it consists of a granuloma composed of histiocytes, epithelioid cells, lymphocytes and some neutrophils Characteristically, the centre of spermatic granuloma contains spermatozoa and necrotic debris
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Vascular disorder Torsion of Testis Twisting of the spermatic cord sudden cessation of venous drainage and arterial supply usually followed by sudden muscular effort or physical trauma Trauma may occure in either in a fully-descended testis or in an undescended testis
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1-Neonatal torsion- occurs either in utero or shortly after birth It lacks any associated anatomic defect in testis 2-“Adult” torsion- is typically seen in adolescence and presents with the sudden onset of testicular pain bell-clapper abnormality -bilateral anatomic defect that leads to increased mobility of the testes (bell-clapper abnormality)
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Viable- manually untwisted within approximately 6 hours of the onset of torsion
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MORPHOLOGIC FEATURES- duration and severity of vascular occlusion may be coagulative necrosis of the testis and epididymis may be haemorrhagic infarction
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Spermatic Cord and Paratesticular Tumors 1-Lipomas common lesions involving the proximal spermatic cord, identified at the time of inguinal hernia repair represent retroperitoneal adipose tissue that has been pulled into the inguinal canal along with the hernia sac, rather than a true neoplasm
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2-Adenomatoid tumor- most common benign paratesticular tumor typically occurring near the upper pole of the epididymis
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grossly , well circumscribed small nodules Microscopically- Proliferation of glandular structures, irregularly lined by cuboidal to flattened epithelial cell Treatmet- local excision
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Malignant tumor rhabdomyosarcomas -children liposarcomas- adults
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CLASSIFICATION OF TESTICULAR TUMOR most useful classification of tumors is histogenetic Named according to from which tissue they arise and of which they consist
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WHO histological classification of testis tumours Germ cell tumours Tumours of one histological type (pure forms) Tumours of more than one histological type (mixed forms) Sex cord/gonadal stromal tumours Pure forms Miscellaneous tumours of the testis Haematopoietic tumours Tumours of collecting ducts and rete Tumours of paratesticular structures Mesenchymal tumours of the spermatic cord and testicular adnexae Secondary tumours of the testis
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Testicular cancer is staged using the TNM system created by the American Joint Committee on Cancer (AJCC) It’s based on 4 key pieces of information: T refers to how much the main (primary) tumor has spread to tissues next to the testicle N describes how much the cancer has spread to regional (nearby) lymph nodes M indicates whether the cancer has metastasized (spread to distant lymph nodes or other organs of the body) S indicates the serum (blood) levels of tumor markers that are made by some testicular cancers
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Letters or numbers appear after T, N, M, and S to provide more details about each piece of information. The numbers 0 through 4 indicate increasing severity The letters “IS” after the T stand for in situ, which means the tumor is contained in one place and has not yet penetrated to a deeper layer of tissue. The letter X after T, N, M, or S means “cannot be assessed” because the information is not known
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TNM classification of germ cell tumours of the testis pTNM pathological classification pTx –Primary tumour cannot be assessed pT0 No evidence of primary tumour (e.g. histologic scar in testis) pTis Intratubular germ cell neoplasia (carcinoma in situ) pT1 Tumour limited to testis and epididymis without vascular/lymphatic invasion; tumour may invade tunica albuginea but not tunica vaginalis pT2 Tumour pT1 + involvement of tunica vaginalis pT3 Tumour invades spermatic cord with or without vascular/lymphatic invasion pT4 Tumour invades scrotum with or without vascular/lymphatic invasion
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pN – Regional lymph nodes pNX Regional lymph nodes cannot be assessed N0 No regional lymph node metastasis pN1 <2 cm or less in greatest dimension and 5 or fewer positive nodes pN2 2 to 5 cm in greatest dimension; or more than 5 nodes positive, none more than 5 cm; or evidence of extranodal extension of tumour pN3 Metastasis with a lymph node mass more than 5 cm in greatest dimension
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S – Serum tumour markers SX Serum marker studies not available or not performed S0 Serum marker study levels within normal limits LDH, hCG (mIU/ml) ,AFP (ng/ml)
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Serum tumor markers (S) For staging, serum (blood) levels of tumor markers are measured after the testicle containing the cancer has been removed with surgery
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Cryptorchidism Cryptorchidism is a complete or partial failure of the intra-abdominal testes to descend into the scrotal sac associated with testicular dysfunction an increased risk of testicular cancer
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In 70% of cases, the undescended testis lies in the inguinal ring in 25% in the abdomen
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ETIOLOGY. exact etiology is not known in majority of cases Mechanical factors- short spermatic cord narrow inguinal canal adhesions to the peritoneum problems with development of the gubernaculum a patent processus vaginalis, or impaired intra-abdominal pressure have also been hypothesized to contribute to cryptorchidism
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2. Genetic factors- up to 23% of cases suggesting an underlying genetic mutation Mutations in insulin-like factor 3 and its receptor, LGR8, have been demonstrated in a small number of cases trisomy 13
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3. Hormonal factor- cryptorchidism is only rarely associated with a well-defined hormonal disorder deficient androgenic secretions mullerian inhibiting substance insulin-like 3 hormone 4. Neuromuscular- abnormalities of the genitofemoral nerve's calcitonin gene-related peptide or the cremasteric nucleus have been postulated to cause cryptorchidism
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Miscellaneous- Maternal alcohol consumption, analgesic consumption, and smoking have also been associated with an increased risk Gestational diabetes has been shown to be related to the development of cryptorchidism
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MORPHOLOGIC FEATURES. Cryptorchidism is unilateral in 80% cases Grossly, the cryptorchid testis is small in size, firm and fibrotic
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Histology- 1-Seminiferous tubules tubular basement membrane is thickened hyalinised tubules with a few Sertoli cells foci of spermatogenesis are discernible in 10% of cases 2. Interstitial stroma: usually increase in the interstitial fibrovascular stroma and conspicuous presence of Leydig cells, seen singly or in small clusters
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CLINICAL FEATURES. asymptomatic and is discovered only on physical examination 1. Sterility-infertility. Bilateral cryptorchidism is associated with sterility while unilateral disease may result in infertility 2. Inguinal hernia. A concomitant inguinal hernia is frequently present along with cryptorchidism
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3-Malignancy. Cryptorchid testis is at 30-50 times increased risk of developing testicular malignancy most commonly seminoma and embryonal carcinoma, than a normally descended testis risk of malignancy is greater in intraabdominal testis than in testis in the inguinal canal
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current recommendations are for correction at 6 to 12 months of age carcinoma arises from foci of intratubular germ cell neoplasia within the atrophic tubules Orchiopexy reduces the risk of sterility and cancer
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Tumour marker Tumour markers- Germ cell tumours of the testis secrete polypeptide hormones and certain enzymes which can be detected in the blood There are two principal serum tumour markers alpha fetoprotein (AFP) and beta subunit of human chorionic gonadotropin (shCG) In addition, carcinoembryonic antigen (CEA), human placental lactogen (HPL), placental alkaline phosphatase, testosterone, oestrogen and luteinising hormone may also be elevated
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AFP- synthesized by fetal yolk sac and also the liver and intestine elevated in 50-70% of testicular germ cell tumours Markedly elevated in yolk sac tumor a serum half life of 4.5 days However, elevated serum AFP levels are also found in liver cell carcinoma hCG- secreted by placental trophoblastic cells elevated in non-seminomatous germ cell tumours of the testis (e.g. in choriocarcinoma, yolk sac tumour and embryonal carcinoma) elevated in 50% of patients with germ cell tumours elevation in seminoma in 10-25% of cases
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Lactate dehydrogenase (LDH)- may also be elevated direct relationship between LDH and tumour burden However, this test is nonspecific although its degree of elevation correlates with bulk of disease
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Applications- In the evaluation of testicular masses In the staging of testicular germ cell tumors. For example, after orchiectomy, persistent elevation of HCG or AFP concentrations indicates stage II disease even if the lymph nodes appear of normal size by imaging studies In assessing tumor burden • In monitoring the respons to therapy. After eradication of tumors there is a rapid fall in serum AFP and HCG. With serial measurements it is often possible to predict recurrence before the patients become symptomatic or develop any other clinical signs of relapse
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TESTICULAR TUMOR
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Testicular tumor Most germ cell tumours occur between the ages of 20 and 50 years Before puberty, seminoma is extremely uncommon usual germ cell tumours , yolk sac tumour and the better differentiated types of teratoma Spermatocytic seminoma and malignant lymphoma usually occur in older patients incidence increases shortly after the onset of puberty and reaches a maximum in men in the late twenties and thirties
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ETIOLOGIC FACTORS Cryptorchidism Other developmental disorders- Dysgenetic gonads associated with endocrine abnormalities such as androgen insensitivity syndrome Genetic factors-high incidence in first-degree family members, twins Other factors. A few less common factors Orchitis Trauma Carcinogens. LSD, hormonal therapy for sterility, copper, zinc etc
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Prenatal risk factors – consistent associations of testicular cancer with low birth weight Exposures in adulthood Possible etiological clues, however, include a low level of physical activity and high socioeconomic class
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PATHOGENESIS-vast majority of these tumours originate from germ cells 1-Developmental disorders- contribute to the pathogenesis 2-Molecular genetic features-common molecular pathogenesis of all germ cell tumours: Hyperdiploidy is almost a constant feature isochromosome of short arm of chromosome 12 Telomerase activity is present in all germ cell tumours of the testis Other mutations include p53, cyclin E and FAS gene
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3-Intratubular germ cell neoplasia (ITGCN) or carcinoma insitu- Most testicular germ cell tumors originate from a precursor lesion called intratubular germ cell neoplasia (ITGCN)exceptions to this rule are pediatric yolk sac tumors Teratomas adult spermatocytic seminoma
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4-Three hit’ process. Germ cells in seminiferous tubules undergo first hit-activate the cell second hit- occure in CIS cell and further activate third hit- via some epigenetic phenomena cell become invasive this sequential tumorigenesis explains the development of seminomatous tumours
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CLINICAL FEATURES AND DIAGNOSIS gradual gonadal enlargement and a dragging sensation in the testis secondary symptoms such as pain, lymphadenopathy, haemoptsis and urinary obstruction (Metastatic involvement ) SPREAD- Lymphatic spread- retroperitoneal para-aortic lymph nodes, mediastinal lymph nodes and supraclavicular lymph nodes Haematogenous spread -primarily occurs to the lungs, liver, brain and bones
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1-Intratubular germ cell neoplasia, unclassified type (IGCNU) Also called carcinoma in situ (CIS) stage of germ cell tumours preinvasive stage of germ cell tumours intratubular seminoma and intratubular embryonal carcinoma are common 2-4% of cryptorchidism pt show Clinical features - atrophic testis, infertility, maldescended testis, and intersex features
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gross- no grossly visible lesion Histopathology - Germ cells with abundant vacuolated cytoplasm, large, irregular nuclei and prominent nucleoli located within the seminiferous tubules restricted to the seminiferous tubules without evident invasion into the interstitium Immunoprofile- PLAP can be demonstrated in 83-99% of intratubular germ cell neoplasia of the unclassified type (IGCNU) cases and is widely used for diagnosis
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Comparison of morphological features of normal seminiferous tubules (left part) and intratubular germ cell neoplasia (IGCNU) in seminiferous tubules (right part).
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Seminoma Seminomas are the most common type of germ cell tumor, making up about (50%) peak incidence is the third decade and they almost never occur in infants An identical tumor arises in the ovary, where it is called dysgerminoma
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.
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MORPHOLOGY- cut surface has a homogeneous, graywhite, lobulated, usually devoid of hemorrhage or necrosis Generally the tunica albuginea is not penetrated but occasionally extension to the epididymis, spermatic cord, or scrotal sac occurs
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Microscopy- typical seminoma is composed of sheets of uniform cells divided into poorly demarcated lobules by delicate fibrous septa containing a lymphocytic infiltrate Tumor cell- cell is large and round to polyhedral and has a distinct cell membrane; clear or watery-appearing cytoplasm; and a large, central nucleus with one or two prominent nucleoli
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Stroma- delicate fibrous tissue which divides the tumour into lobules characteristic lymphocytic infiltration, indicative of immunologic response of the host to the tumour Variable features- tumor giant cells and greater mitotic activity 15% of seminomas contain syncytiotrophoblasts ill-defined granulomatous reaction (20%)
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Special stain-Cytoplasm contains variable amount of glycogen that stains positively with PAS reaction IHC- seminoma cells stain positively for KIT, (regardless of KIT mutational status), OCT4, and placental alkaline phosphatase (PLAP)
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Prognosis- better than other germ cell tumours tumour is highly radiosensitive
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Spermatocytic Seminoma- Spermatocytic seminoma is both clinically and morphologically a distinctive tumour from classic seminoma Incidence of about 5% of all germ cell tumours older patients generally in 6th decade of life bilateral in 10% of patients
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Grossly, spermatocytic seminoma is homogeneous, larger, softer and more yellowish and gelatinous than the classic seminoma
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Histologically, the distinctive features are as under: 1. Tumour cells. lymphocyte-like to huge mononucleate or multinucleate giant cells. Majority of cells are, however, of intermediate size. Mitoses are often frequent. 2. Stroma. stroma lacks lymphocytic and granulomatous reaction seen in classic seminoma.
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prognosis of spermatocytic seminoma is excellent slow-growing and rarely metastasises tumour is radiosensitive
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Embryonal Carcinoma- 30% of germ cell tumours more common 2nd to 3rd decades of life 90% cases are associated with elevation of AFP or hCG or both
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Grossly,- a small tumour in the testis distorts the contour of the testis as it frequently invades the tunica and the epididymis Cut surface- greywhite, soft with areas of haemorrhages and necrosis
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Microscopy- 1. tumour cells are arranged in a variety of patterns— glandular, tubular, papillary and solid 2.tumour cells are highly anaplastic carcinomatous cells having large size, indistinct cell borders, amphophilic cytoplasm and prominent hyperchromatic nuclei
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Yolk Sac Tumour (Synonyms: Endodermal Sinus Tumour, Orchioblastoma, Infantile Embryonal Carcinoma) most common testicular tumour of infants and young children upto the age of 4 year may be present as the major component in 40% of germ cell tumours AFP levels are elevated in 100% cases of yolk sac tumours
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Grossly, the tumour is generally soft, yellow-white, mucoid with areas of necrosis and haemorrhages Microscopically, yolk sac tumour has the following features patterns—loose reticular network, papillary, tubular and solid arrangement 2. flattened to cuboid epithelial cells with clear vacuolated cytoplasm 3.A pathognomonic feature is Schiller -Duvel body a central vessel surrounded by tumor cells in a cystic space often lined by flattened tumor cells 4. presence of both intracellular and extracellular PAS-positive hyaline globules
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Choriocarcinoma highly malignant tumour composed of syncytiotrophoblast and cytotrophoblast 2nd decade of life serum and urinary levels of hCG are greatly elevated in 100% cases
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Grossly, the tumour is usually small and may appear as a soft, haemorrhagic and necrotic mass Microscopically, the characteristic feature is syncytiotrophoblast and cytotrophoblast without formation of definite placental-type villi
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Teratoma- Teratomas are complex tumours composed of tissues derived from more than one of the three germ cell layers—endoderm, mesoderm and ectoderm more common in infants and children and constitute ( 40%) in adults they comprise 5% of all germ cell tumours
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MORPHOLOGIC FEATURES. Testicular teratomas are classified into 3 types: 1. Mature (differentiated) teratoma 2. Immature teratoma 3. Teratoma with malignant transformation
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Gross- large, grey-white masses enlarging testis Cut surface shows characteristic variegated appearance—grey-white solid areas, cystic and honey-combed areas, and foci of cartilage and bone
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Germ cell layer derivatives
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Microscopicy- three categories of teratomas show different appearances: 1-Mature (differentiated) teratoma. Well differentiated structures such as cartilage, smooth muscle, intestinal and respiratory epithelium, mucus glands, cysts lined by squamous and transitional epithelium, neural tissue, fat and bone
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2-Immature teratoma. incompletely differentiated and primitive or embryonic tissues along with some mature elements present are poorly-formed cartilage, mesenchyme, neural tissues, abortive eye, intestinal and respiratory tissue elements etc Mitoses are usually frequent
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Immature stroma
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3-Teratoma with malignant transformation- extremely rare form of teratoma one or more of the tissue elements show malignant transformation Transformation may take the form of a squamous cell carcinoma, mucin-secreting adenocarcinoma, sarcoma, or other cancers. importance of recognizing a non–germ cell malignancy arising in a teratoma is that these secondary tumors are chemoresistant
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Mixed Germ Cell Tumours About 60% of germ cell tumours have more than one of the above histologic types (except spermatocytic seminoma) and are called mixed germ cell tumours most common combinations of mixed germ cell tumours are as under: 1. Teratoma, embryonal carcinoma, yolk sac tumour and syncytiotrophoblast 2. Embryonal carcinoma and teratoma (teratocarcinoma) 3. Seminoma and embryonal carcinoma
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SEX CORD-STROMAL TUMOURS-Tumours arising from specialised gonadal stroma primitive mesenchyme>>> specialised stroma of gonads in either sex gives rise to theca, granulosa and lutein cells in the female Sertoli and interstitial Leydig cells in the male
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Leydig (Interstitial) Cell Tumour- 20 to 50 yr, secrete androgen, or both androgen and oestrogen Grossly, as a small, well-demarcated and lobulated nodule. Cut surface is homogeneously yellowish or brown Histologically, the tumour is composed of sheets and cords of normal-looking Leydig cells These cells contain abundant eosinophilic cytoplasm and Reinke’s crystals and a small central nucleus
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Sertoli Cell Tumours (Androblastoma)- infants and children Oestrogen or androgen gynaecomastia in an adult precocious sexual development in a child
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Grossly, the tumour is large, firm, round, and well circumscribed. Cut surface is yellowish or yellow-grey Microscopically, Sertoli cell tumour is composed of benign Sertoli cells arranged in well-defined tubules
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MIXED GERM CELL-SEX CORD STROMAL TUMOURS- Gonadoblastoma- secrete androgen Grossly, the tumour is of variable size, yellowish-white and soft Microscopically, gonadoblastoma is composed of 2 principal cell types—large germ cells resembling seminoma cells, and small cells resembling immature Sertoli, Leydig and granulosa cells
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OTHER TUMOURS Malignant Lymphoma- comprises 5% of testicular malignancies most common testicular tumour in the elderly Bilaterality is seen in half the cases Most common are large cell non-Hodgkin’s lymphoma of B cell type
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Must know 1-classification 2-Tumor markers in diagnosis 3-Morphology of Seminoma Embryonal carcinoma Yolk sac tumor 4-Cryporchidism