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and received cisplatin therapy&#46; At recent check-up&#44; CT scans revealed some enlargement of known lung lesions&#59; blood alpha-fetoprotein levels were also slightly elevated &#40;AFP&#58; 9<span class="elsevierStyleHsp" style=""></span>ng&#47;ML&#41;&#46; Since needle-biopsy findings were inconclusive&#44; lung nodules were all excised by videothoracoscopy&#46; Histological examination of them revealed a multicystic lesion containing solid areas&#46; The cystic component was lined by squamous&#44; respiratory and intestinal epithelium&#44; a finding consistent with a mature teratoma&#46; The solid component comprised tumor cell nests displaying peripheral pallisading&#44; an organoid arrangement with rosette formation&#44; focal necrosis and a high mitotic rate &#40;6&#47;10 HPF&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>A&#41;&#46; No elements characteristic of immature teratoma were observed&#46; Immunohistochemical analysis revealed patchy focal positivity for CK7&#44; CK20&#44; CDX2 and SOX2 in the cylindrical epithelial cells of the cystic component &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>B and C&#41;&#46; Solid-component cells stained positive for cytokeratin &#40;AE1&#47;AE3&#41;&#44; chromogranin-A &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>D&#41;&#44; synaptophysin&#44; and cytoplasmic OCT4&#44; and negative for CD56&#46; Staining for neural development transcription factors &#40;TTF1&#44; ASCL1 and POU3F2&#41; was positive only for POU3F2 &#40;nuclear&#41;&#46; Since tests using a broad battery of antibodies &#40;CDX2&#44; TTF1&#44; CK7 and CK20&#41; yielded negative results&#44; it was not possible to identify the original tissue of the neuroendocrine component&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">The final pathological diagnosis was atypical carcinoid tumor in a metastatic mature cystic teratoma&#46; Surgical margins were tumor free&#44; and postoperative recovery was good&#44; with no complications&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Two histogenetic hypotheses have been put forward to account for this association&#46; The first is that cisplatin therapy selectively excludes immature components&#44; whilst chemotherapy-resistant mature components survive and in some cases grow&#46; The second is that chemotherapy induces the transformation of immature malignant teratoma into mature teratoma&#44; a phenomenon first reported by DiSaia et al&#46; in ovarian GCTs&#44; and termed chemotherapeutic retroconversion&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">3</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Somatic-type malignancy occurs in 3&#8211;6&#37; of GCTs&#44; almost always in postpubertal patients &#40;aged 15&#8211;68&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">1&#44;2&#44;4</span></a> Although most affected patients have teratomatous GCTs&#44;<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">1&#44;2&#44;5</span></a> somatic-type malignancy has occasionally been reported in other germ-cell tumors including yolk-sac and spermatocytic tumors&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">6</span></a> The time elapsing between GTC diagnosis and the appearance of STMs tends to vary widely&#44; ranging from simultaneous presentation to a latency period of up to 30 years&#46; The interval for carcinomas &#40;108 months&#41; is longer than for sarcomas &#40;20 months&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">5</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">Reported STMs include various types of sarcoma&#44; epithelial malignancies and hematological malignancies&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">7</span></a> Sarcomas are undoubtedly the most common type of malignancy&#59; although rhabdomyosarcomas account for over half the STMs recorded&#44; leiomyosarcomas&#44; angiosarcomas and other STMs have occasionally been reported&#46;<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">8&#44;9</span></a> Carcinomas tend to be mostly to be classed as adenocarcinomas NOS<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">6</span></a>&#59; there are very few reports of neuroendocrine tumors&#44; particularly in testicular lesions&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Generally speaking&#44; the prognosis for these tumors is not affected when the STM is located in the testicle&#59; however&#44; development of STM in metastases&#8212;as in the present case&#8212;is associated with an increased risk of mortality&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">8</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">The role of chemotherapy in teratomas with malignant neuroendocrine transformation has not been fully established&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">7</span></a> Complete surgical resection has traditionally been the treatment of choice when malignant transformation occurs at a single site&#46; Metastatic or unresectable tumors will generally require multimodal management including chemotherapy in addition to loco-regional approaches&#46; Although patients tend to respond poorly to cisplatin-based treatments&#44; some tumors may respond to the specific chemotherapy used for the somatic counterpart&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">10</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">Summarizing&#44; in this rare case a patient with mixed germ-cell tumor of the testis and metastasis&#44; treated with chemotherapy&#44; seven years later developed an atypical carcinoid tumor&#44; with a somatic-like malignant component&#44; in a metastatic mature cystic teratoma of the lung&#46; Comprehensive pathological examination is essential for the identification of somatic neoplasms within germ cell tumor metastases&#46;</p></span>"
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Scientific Letter
Mature Cystic Teratoma of the Lung With a Somatic-Like Malignant Component in a Patient With Testicular Germ-Cell Tumor
Teratoma quístico maduro de pulmón con componente maligno de tipo somático en un paciente con un tumor testicular de células germinales
Ana Vallejo-Beníteza,
Corresponding author
anvaben@hotmail.com

Corresponding author.
, Enrique Rodríguez-Zarcoa, Sofia Pereira-Gallardoa, Laura Macías-Garcíab
a Hospital Universitario Virgen Macarena, Seville, Spain
b Department of Cytology and Histology Normal and Pathological, University of Seville, Seville, Spain
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">In urological oncology&#44; the diagnosis of <span class="elsevierStyleItalic">teratoma with a somatic-like malignant component</span> refers to the presence of a malignant neoplasm&#44; e&#46;g&#46; carcinoma or sarcoma&#44; either within a teratoma of the genital tract &#40;usually the testis&#41; or&#44; more commonly&#44; in a metastasis&#44; following initial cisplatin therapy&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> The somatic-type malignancy &#40;STM&#41; most widely observed in germ cell tumors &#40;GCT&#41; is rhabdomyosarcoma&#59; neuroendocrine carcinoma is extremely rare&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">We report on a 40-year-old patient who had undergone surgery seven years earlier for a malignant mixed germ-cell tumor of the right testicle with pulmonary and retroperitoneal metastasis&#44; and received cisplatin therapy&#46; At recent check-up&#44; CT scans revealed some enlargement of known lung lesions&#59; blood alpha-fetoprotein levels were also slightly elevated &#40;AFP&#58; 9<span class="elsevierStyleHsp" style=""></span>ng&#47;ML&#41;&#46; Since needle-biopsy findings were inconclusive&#44; lung nodules were all excised by videothoracoscopy&#46; Histological examination of them revealed a multicystic lesion containing solid areas&#46; The cystic component was lined by squamous&#44; respiratory and intestinal epithelium&#44; a finding consistent with a mature teratoma&#46; The solid component comprised tumor cell nests displaying peripheral pallisading&#44; an organoid arrangement with rosette formation&#44; focal necrosis and a high mitotic rate &#40;6&#47;10 HPF&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>A&#41;&#46; No elements characteristic of immature teratoma were observed&#46; Immunohistochemical analysis revealed patchy focal positivity for CK7&#44; CK20&#44; CDX2 and SOX2 in the cylindrical epithelial cells of the cystic component &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>B and C&#41;&#46; Solid-component cells stained positive for cytokeratin &#40;AE1&#47;AE3&#41;&#44; chromogranin-A &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>D&#41;&#44; synaptophysin&#44; and cytoplasmic OCT4&#44; and negative for CD56&#46; Staining for neural development transcription factors &#40;TTF1&#44; ASCL1 and POU3F2&#41; was positive only for POU3F2 &#40;nuclear&#41;&#46; Since tests using a broad battery of antibodies &#40;CDX2&#44; TTF1&#44; CK7 and CK20&#41; yielded negative results&#44; it was not possible to identify the original tissue of the neuroendocrine component&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">The final pathological diagnosis was atypical carcinoid tumor in a metastatic mature cystic teratoma&#46; Surgical margins were tumor free&#44; and postoperative recovery was good&#44; with no complications&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Two histogenetic hypotheses have been put forward to account for this association&#46; The first is that cisplatin therapy selectively excludes immature components&#44; whilst chemotherapy-resistant mature components survive and in some cases grow&#46; The second is that chemotherapy induces the transformation of immature malignant teratoma into mature teratoma&#44; a phenomenon first reported by DiSaia et al&#46; in ovarian GCTs&#44; and termed chemotherapeutic retroconversion&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">3</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Somatic-type malignancy occurs in 3&#8211;6&#37; of GCTs&#44; almost always in postpubertal patients &#40;aged 15&#8211;68&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">1&#44;2&#44;4</span></a> Although most affected patients have teratomatous GCTs&#44;<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">1&#44;2&#44;5</span></a> somatic-type malignancy has occasionally been reported in other germ-cell tumors including yolk-sac and spermatocytic tumors&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">6</span></a> The time elapsing between GTC diagnosis and the appearance of STMs tends to vary widely&#44; ranging from simultaneous presentation to a latency period of up to 30 years&#46; The interval for carcinomas &#40;108 months&#41; is longer than for sarcomas &#40;20 months&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">5</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">Reported STMs include various types of sarcoma&#44; epithelial malignancies and hematological malignancies&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">7</span></a> Sarcomas are undoubtedly the most common type of malignancy&#59; although rhabdomyosarcomas account for over half the STMs recorded&#44; leiomyosarcomas&#44; angiosarcomas and other STMs have occasionally been reported&#46;<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">8&#44;9</span></a> Carcinomas tend to be mostly to be classed as adenocarcinomas NOS<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">6</span></a>&#59; there are very few reports of neuroendocrine tumors&#44; particularly in testicular lesions&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Generally speaking&#44; the prognosis for these tumors is not affected when the STM is located in the testicle&#59; however&#44; development of STM in metastases&#8212;as in the present case&#8212;is associated with an increased risk of mortality&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">8</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">The role of chemotherapy in teratomas with malignant neuroendocrine transformation has not been fully established&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">7</span></a> Complete surgical resection has traditionally been the treatment of choice when malignant transformation occurs at a single site&#46; Metastatic or unresectable tumors will generally require multimodal management including chemotherapy in addition to loco-regional approaches&#46; Although patients tend to respond poorly to cisplatin-based treatments&#44; some tumors may respond to the specific chemotherapy used for the somatic counterpart&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">10</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">Summarizing&#44; in this rare case a patient with mixed germ-cell tumor of the testis and metastasis&#44; treated with chemotherapy&#44; seven years later developed an atypical carcinoid tumor&#44; with a somatic-like malignant component&#44; in a metastatic mature cystic teratoma of the lung&#46; Comprehensive pathological examination is essential for the identification of somatic neoplasms within germ cell tumor metastases&#46;</p></span>"
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Article information
ISSN: 15792129
Original language: English
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