Primary non gestational extra gonadal choriocarcinoma of the lung


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Primary non gestational extra gonadal choriocarcinoma of the lung

  1. 1. Primary Non Gestational Extra- gonadal Choriocarcinoma of the Lung By: Muhamad Na’im B. Ab Razak, Universiti Sains Malaysia Choriocarcinoma is a germ cell tumor containing syncytiotrophoblastic giant cells and often secreting a biological tumor marker (β-HCG). [Jong-Rung Tsai et al, 2002]. It is basically classified as gestational and non gestational. Simply put, gestational choriocarcinoma arises from or in association with a gestational event. In this form, the placenta is the site of origin of the tumor. The incidence increases after spontaneous abortions or a molar pregnancy or ectopic pregnancy. [Vadivel Ganapathy et al, 1999] A rare form of gonadal choriocarcinoma, called neonatal or infantile choriocarcinoma may develop in the baby during the neonatal period. This lesion is originally thought to arise from placenta which metastasizes to other part of fetal organ in vitro. Meanwhile, non gestational choriocarcinoma or primary carcinoma is the similar pathology which develops without any relation to pregnancy. It occurs in extra placental tissue of non gravid uterus and may be classify as either gonadal or extra gonadal type. Compared to gestational choriocarcinoma, non gestational choriocarcinoma is extremely rare but it can occur in both male and female. In female, it should be listed as one of the differential diagnosis when patient presented with amenorrhea or sign and symptoms of pregnancy but without clinical and sonographic finding of intrauterine or ectopic pregnancy. Apart from that, pregnancy of unknown location may be suspected as well. However, if β-HCG persistently high even after treatment for pregnancy of unknown location, therefore non gestational choriocarcinoma is most likely. Gonadal Choriocarcinoma arise from testis in male and ovary in females. Tumor arises from testis is more common world widely as compared to the ovary and may occur together with seminoma, teratoma, and embryonal carcinoma. Primary (non-gestational) choriocarcinoma of the ovary is an uncommon condition and accounts for less than 0.6% of all ovarian tumors. It occurs most frequently as a component of a mixed germ cell tumour, and the presence of other germ cell elements establishes the non-gestational origin of the tumour. [P.C. Lorigan et al, 1996] Extragonadal germ cell tumors are rare, and most of them occur in the midline structures such as sacrum, mediastinal, and the central nervous system. [Huaiyin Shi et al, 2009] One of the least common sites is the lung [M.A. Corpa Rodriguez et al, 2009] with the reported case are less than 30. Other rare sites include liver, peritoneum, small intestine, prostate and urinary bladder. Before diagnosing the Extragonadal germ cell tumor as a primary pathology, one needs to exclude the possibility of the metastasis from the gonadal choriocarcinoma.
  2. 2. Because the lung is a frequent site of metastatic choriocarcinoma, the diagnosis of the primary tumor should be made carefully. [Jong-Rung T et al, 2002]. Magrath, Golding and Bagshawe found that 36 of 179 patients had pulmonary presenting symptoms. [Robert P et al, 1979] Common presentations are respiratory symptoms like cough, recurrent haemoptysis, pleuritic chest pain and shortness of breath together with persistently high serum β-HCG level. Female patients may present with hormonal problems such as amenorrhoea, vaginal spotting or genital bleeding. [Usha Kini& M.K Babu, 2006] Apart from that, patient may also presented with endocrine symptoms [Usha Kini& M.K Babu, 2006] and male may have signs of feminization like gynecomastia, loss of libido, and testicular atrophy. [Anna Arslanian et al, 2003]. Bleeding tendency of the primary and metastatic sites and the constant elevation of serum β-HCG levels are two entities defining choriocarcinoma syndrome. The origin of this type of tumor is not clear, although a range of theories have been put forward. [M.A. Corpa Rodriguez et al, 2009] In a literature by Holt et al, 1965, they listed 5 theories that contribute to the origin of extra gonadal choriocarcinoma which includes 1) originate from teratoma, 2) Origin from a "germinal rest" either of toti-potential cells left during the blastula or morula stage of embryonic development or from primordial germ-cell rests, which, on separating from the urogenital ridge in embryo, did not complete the migration to the site of the normal testis, 3) Originate from primitive mesenchymal cells, 4) Originate from a dormant trophoblastic embolus acquired in fetal life, and 5) Metaplasia and dedifferentiation of a carcinoma or that embryonal carcinoma is a stage in the development of choriocarcinoma and that embryonal carcinomata themselves arise from multipotential cells. Autopsies performed on women who died during birth or after miscarriage have found trophoblastic cells in pulmonary arteries, suggesting that choriocarcinoma of the lung in women could be due to pulmonary embolization caused—during birth or miscarriage—by these cells, which might subsequently become malignant. The tumor may even appear years later. [M.A. Corpa Rodriguez et al, 2009] The diagnostic criteria of the primary non gestational choriocarcinoma of the lung would include lack of a previous gynecologic malignancy, solitary or predominant lung lesion with the exclusion of a gonadal primary site, raised serum β-HCG level titers that become normal after surgery or chemotherapy, and pathologic confirmation of the disease. [Anna Arslanian et al, 2003] Hematologic analysis shows also leukocytosis with neutrophilia and elevated sedimentation rate. Although urinary β-HCG has considerable diagnostic and prognostic value, a negative test result does not exclude presence of these neoplasms. [Anna Arslanian et al, 2003] Urine pregnancy test is a simple and convenient method that would be very useful in the rapid diagnosis of primary pulmonary choriocarcinoma. [Jong-Rung Tsai et al, 2002]
  3. 3. Imaging features may include well defined solitary lobulated opacity located at the central part in relation to bronchus, mediastinal shift to the opposite side, collapse of any adjacent tissue, peripheral ground glass opacity due to pulmonary hemorrhage and co exist pleural effusion. Multiple nodule and mediastinal or hilar lymphadenopathy is uncommon. In the asymptomatic patient, pulmonary mass could be an incidental finding at routine chest x ray. [Usha Kini& M.K Babu, 2006] CT can identify the lung lesion better and assess whether enlarged lymph nodes are present. Fiberoptic bronchoscopy can also be done, although the result may be negative. Fine-needle percutaneous biopsy will often reveal cells considered as squamous. Definitive diagnosis is histological, after lung biopsy, although it is not uncommon to reach a diagnosis after analyzing the resected specimen when another type of tumor with a more common histology had been suspected. Sometimes, diagnosis is made at autopsy. [M.A. Corpa Rodriguez et al, 2009] Histopathology examination may shows the present of malignant cells resembling either cytothrophoblast or multinucleate syncytiotrophoblast cells with large and bizarre nuclei which arrange themselves in alternating layers to mimic the structure of chorionic villi. However, true chorionic villi are not present. Area of necrosis and hemorrhage usually present due to the tendency of the trophoblastic cells to invade the blood vessel walls. This may explain why this malignancy is highly metastasizing to other part of the body. As for the treatment, there is no standardized regime for chemotherapy due to the rarity of this problem. EMA-CO (etoposide, methotrexate, actinomycin D, cyclophosphamide, and vincristine) regime may be used as well as regime for treating non small cell lung cancer which is bleomycin, etoposide, and cisplatin. In a low risk patient, treatment with methotrexate, folinic acid and actinomycin D may be justified. A return to normal β-hCG levels after therapy is indicative of good response, and increasing levels may point to recurrence. For monitoring and detection of recurrences, regular β-hCG measurements and radiological examinations should be performed. The prognosis of primary tumor of the lung is worst as compared to gestational choriocarcinoma because of its rapid progression and spread, mainly to the brain and kidney. The outcome is usually fatal and the prognosis poor despite treatment, with survival of less than 1 year in most cases. According to Umemori et al, mean survival is 5 months and the survival at 1 year 34.6% (9 patients). The 2 cases described previously also had a fatal outcome. [M.A. Corpa Rodriguez et al, 2009]
  4. 4. Reference: 1) Alan Stevens, James S. Lowe & Barbara Young, “Wheather’s Basic Histopathology; A Colour Atlas and Text”, 4th edition, Churchill Livingstone, 2002. 2) Anna Arslanian, Franco Pischedda, Pier Luigi Filosso et al, "Primary choriocarcinoma of the lung", J Thorac Cardiovasc Surg, 125:193-196, 200 3) A.S. Gremeau, N. Bourdel, W. Kondo et al, "Management of non-gestational ovarian choriocarcinoma: laparoscopy can be essential. Report of two cases.", Letters to the Editor / European Journal of Obstetrics & Gynecology and Reproductive Biology 152:111–114, 2010 4) Enrique Lastra Aras, Pilar Garrido López, Juan Lago & Ignacio Muguruza, "Primary lung choriocarcinoma", Rev Oncología, 3: 107-109, 2001. 5) Huaiyin Shi, Dengfeng Cao, Lixin Wei, Lu Sun & Aitao Guo "Primary choriocarcinoma of the liver: a clinicopathological study of five cases in males", Virchows Arch (2010) 456:65–70, Springer-Verlag 2009 6) Jong Rung Tsai, Inn Wen Chong, Jen Yu Hung & Kun Bow Tsai, "Use of Urine Pregnancy Test for Rapid Diagnosis of Primary Pulmonary Choriocarcinoma in a Man", CHEST 2002; 121:996–998 7) L. P. Holt, D. H. Melcher & J. Colquhoun "Extra- Gonadal Choriocarcinoma In The Male", Postgrad. Med. J, 41:134, 1965 8) María Elena Corpa Rodríguez, Juan Fernández Lahera, Héctor Guadalajara Labajo et al, "Choriocarcinoma of the Lung", Archivos de Bronconeumología (English Edition), Volume 45, Issue 3, Pages 157-159, March 2009. 9) P.C. Lorigan, A.J. Grierson, J.R. Goepel, R.E. Coleman & M.H. Goyn, "Gestational choriocarcinoma of the ovary diagnosed by analysis of tumour DNA", Cancer Letters, 104:27-30, 1996 10) Robert P. Stevens, Thomas H. Peirc, Parker C. Dooley & Gibbe H. Parsons, "Bilateral spontaneous pneumothorax in nongestational choriocarcinoma", CMA Journal, volume 120: April 7, 1979 11) Tomoyoshi Shibuya, Taro Osada1, Tomohiro Kodani, et al "Gastrointestinal Hemorrhage as the First Manifestation of Metastatic Extragonadal Choriocarcinoma", Inter Med 48: 551-554, 2009 12) Usha Kini & M.K. Babu, " Primary Pulmonary Choriocarcinoma: Is It Still an Enigma?", The Indian Journal of Chest Diseases & Allied Sciences volume 49, 2007 13) Vadivel Ganapathy, Puttur D. Prasad & Frederick H. Leibach, "Choriocarcinoma", Human Cell Culture Vol. 11, 141 –147, Kluwer Academic Publishers, 1999. 14) Willem K. Brouwer, Hans A. van Raalte, Henk van Veelen, et al, "An extra gonadal non- gestational choriocarcinoma in a woman treated for an endometrial carcinoma", European Journal of Obstetrics & Gynecology and Reproductive Biology 60: 195-199, Elsevier Science Ireland Ltd, 1995