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Pulmonary-type adenocarcinoma and signet ring mucinous adenocarcinoma arising in an ovarian dermoid cyst: report of a unique case
Human Pathology (2012) 43, 2088–2092
www.elsevier.com/locate/humpath
Case study
Pulmonary-type adenocarcinoma and signet ring mucinous adenocarcinoma arising in an ovarian dermoid cyst: report of a unique case Clinton Boyd FRCPath a , Kaushik Patel FRCPath b , Brendan O'Sullivan FRCPath c , Philippe Taniere FRCPath c , W. Glenn McCluggage FRCPath a,⁎ a
Department of Pathology, Belfast Health and Social Care Trust and Molecular Pathology Programme, Centre for Cancer Research and Cell Biology, Queens University Belfast, BT12 6BA Belfast, UK b Department of Pathology, Kingston Hospital, Surrey, KT2 Kingston, UK c Department of Pathology, University Hospital of Birmingham, B15 2TG Birmingham, UK Received 1 April 2012; accepted 29 May 2012
Keywords: Ovary; Dermoid cyst; Mucinous adenocarcinoma; Pulmonary adenocarcinoma
Summary Dermoid cysts are common benign ovarian germ cell neoplasms. Occasionally, one of the mature elements undergoes malignant transformation resulting in the formation of a somatic malignancy; most commonly this is squamous carcinoma. We report a unique case where 2 separate malignancies arose within a dermoid cyst, one a signet ring mucinous adenocarcinoma and the other a pulmonary-type adenocarcinoma. There have been only occasional earlier case reports of a possible pulmonary-type adenocarcinoma arising in a dermoid cyst. In the case we report, the pulmonary-type adenocarcinoma was closely associated with a bronchial structure and exhibited diffuse positive immunohistochemical staining with TTF1, PE10, and napsin A. Molecular studies revealed no evidence of epidermal growth factor receptor mutation, a molecular alteration which may be found in primary pulmonary adenocarcinoma. © 2012 Elsevier Inc. All rights reserved.
1. Introduction Dermoid cysts (mature cystic teratomas) are common ovarian germ cell neoplasms composed of an admixture of mature elements of multiple types. Uncommonly, one of the elements undergoes malignant transformation resulting in the formation of a somatic neoplasm. Most commonly, this is a squamous carcinoma [1,2]. Adenocarcinomas, especially of mucinous type, have also been reported in association ⁎ Corresponding author. E-mail address: [email protected] (W. G. McCluggage). 0046-8177/$ – see front matter © 2012 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.humpath.2012.05.027
with and arising from teratomas [3-5]. In this report, we describe a unique case where a signet ring mucinous adenocarcinoma and a pulmonary-type adenocarcinoma both arose within a dermoid cyst; as far as we are aware, there have been only 3 earlier case reports of a possible pulmonary-type adenocarcinoma arising in an ovarian teratoma [6-8].
2. Case report A 35-year-old woman presented with pain in the left side of her vagina. Her past medical history included recurrent
Pulmonary-type and signet ring mucinous adenocarcinoma
2089
Fig. 1 Large intestinal mucosa (A), benign mucinous glands (B), and signet ring mucinous adenocarcinoma (C); the latter is diffusely positive with CK20 (D).
miscarriages and antiphospholipid syndrome. She had underwent bilateral ovarian cystectomies 10 years previously, and histology of both ovaries had shown dermoid cysts (it was not possible to review the slides of these). Following this, she was followed up by ultrasound scans and discharged after 3 years. An ultrasound scan before her latest admission showed an unremarkable anteverted uterus and a cystic right ovary measuring 52 × 20 × 41 mm. The left ovary measured 40 × 20 × 30 mm and contained several small cysts. She underwent laparoscopy which confirmed bilateral ovarian cysts. A right ovarian cystectomy with preservation of ovarian tissue and left oophorectomy was performed with the presumptive diagnosis of recurrent bilateral dermoid cysts.
3. Pathological findings The left ovary measured 38 × 25 × 25 mm. Sectioning revealed a unilocular cyst containing hair and sebaceous material. The right ovary was received as multiple pieces of tissue, the largest measuring 85 mm in maximum dimension. These were partly cystic and partly solid.
Histology of the left ovary showed features of a dermoid cyst (mature cystic teratoma). Elements present were skin with underlying skin appendage structures and adipose tissue. There were no immature or malignant elements. Multiple sections from the right ovary were examined histologically. They showed a residual dermoid cyst with skin and underlying skin appendage structures. Large intestinal-type mucosa was also present (Fig. 1A). In addition, many of the sections showed a mucinous neoplasm with a variable histological appearance. There were benign cysts and glands lined by a single layer of bland mucinous epithelium, areas of epithelial proliferation involving the lining of cysts, in keeping with borderline mucinous tumor of intestinal type, and foci of invasive adenocarcinoma. In areas, the adenocarcinoma was composed of well formed glands but there were also elements of signet ring adenocarcinoma. The features were those of an intestinal (enteric)–type mucinous tumor with benign, borderline and malignant elements. Fig. 1B and C illustrate representative areas of the mucinous neoplasm. The malignant mucinous elements, including the signet ring cells, were diffusely positive with cytokeratin 20 (CK20) (Fig. 1D), CEA, CDX2, and CA19.9. CK7 was only very focally positive in the
2090 malignant component, although the benign and borderline mucinous elements were diffusely positive. Estrogen receptor (ER), CA125, and PAX8 were negative in the mucinous elements. In addition to the mucinous elements, a morphologically distinct tumor was present. This comprised an adenocarcinoma with infiltrative glandular structures and solid arrangements of cells with no intracytoplasmic mucin. The cells contained moderately atypical nuclei with prominent nucleoli and a scant to moderate amount of eosinophilic cytoplasm (Fig. 2A). This adenocarcinoma was intimately related to and appeared to be arising from a bronchial structure lined by ciliated epithelium with extensive squamous metaplasia (Fig. 2B). In some areas, the 2 types of adenocarcinoma were intermingled, but for the most part, they were separate and they were clearly morphologically distinct. The nonmucinous adenocarcinoma exhibited diffuse CK7 positivity and was negative for CK20, CEA, CDX2, CA19.9, CA125, PAX8, and ER. There was diffuse positive nuclear staining with TTF1. Napsin A and PE10 were also diffusely positive. The immunohistochemical features were in keeping with a pulmonary-type adenocarcinoma. Fig. 3 illustrates various immunohistochemical stains within the pulmonary-type adenocarcinoma component.
4. Molecular analysis and findings A representative paraffin block containing the pulmonary type adenocarcinoma was tested for epidermal growth factor receptor (EGFR) mutations. The paraffin block was sectioned under sterile laboratory conditions. A single 3μm section was stained to allow assessment of appropriate tumor-rich areas suitable for DNA extraction. DNA extraction was performed using the Qiagen QIAmp FFPE Tissue Kit; a single 6-μm section was digested overnight. Mutation analysis was performed using the Qiagen Ther-
C. Boyd et al. ascreen kit. The EGFR analysis detects mutations in regions of exons 18, 19, 20, and 21 of the EGFR1 gene (known to contain clinically relevant mutations associated with drug sensitivity). EGFR was wild type with no pathogenic mutations found.
5. Discussion Dermoid cysts (mature cystic teratomas) are common ovarian neoplasms, particularly in women of reproductive age, and are by a significant margin the most common type of ovarian germ cell tumor. A wide range of tissues derived from all 3 germ cell layers may be present but some tissue types are found more commonly than others. Skin, skin appendage structures, smooth muscle, and adipose tissue are among the most commonly identified elements. Glial tissue, choroid plexus, nerves, gastrointestinal and bronchial tissue, thyroid, cartilage, and bone are less frequent but still relatively common. Any of the mature tissue components within a dermoid cyst can in theory undergo malignant transformation. Malignant transformation is rare, probably occurring in less than 1% of these neoplasms and by far the most frequent somatic malignancy to develop within these tumors is squamous cell carcinoma, which accounts for approximately 75% of cases of malignant transformation [1,2] Less common tumor types include adenocarcinoma, undifferentiated carcinoma, sebaceous carcinoma, thyroid-type tumors, carcinoid tumor, various sarcomas, glial neoplasms, and malignant melanoma [9-16]. Most adenocarcinomas are of intestinal mucinous type, sometimes with associated benign and borderline elements (the full range of mucinous neoplasms from benign to borderline to malignant can arise in association with a dermoid cyst), but more uncommon variants of adenocarcinoma reported include a single case of a prostatic-type adenocarcinoma [17]. Reports
Fig. 2 Pulmonary type adenocarcinoma composed of glandular and solid arrangements of cells (A). A bronchial-type structure is present lined by respiratory epithelium exhibiting squamous metaplasia (B).
Pulmonary-type and signet ring mucinous adenocarcinoma
Fig. 3
2091
The pulmonary-type adenocarcinoma is diffusely positive for CK7 (A), TTF1 (B), PE10 (C), and napsin A (D).
of 2 separate malignancies arising in a dermoid cyst are exceedingly rare, although there has been 1 report of a squamous carcinoma and a microcystic adnexal carcinoma and another of a leiomyosarcoma and squamous cell carcinoma in situ [18,19]. In the case we report, the 2 adenocarcinoma components were focally intermingled but for the most part they were separate and were morphologically and immunophenotypically clearly distinct. One adenocarcinoma comprised an intestinal-type mucinous adenocarcinoma with signet ring cells and benign and borderline elements. The second adenocarcinoma was morphologically different and was intimately associated with and probably arose from a bronchial structure. This adenocarcinoma was diffusely positive with CK7 and also with TTF1, PE10, and napsin A. Although none of these antibodies is totally specific [20,21], they are all markers of primary pulmonary adenocarcinoma. Given the association with a bronchial structure and the diffuse immunoreactivity with the 3 pulmonary markers mentioned, it is clear that this component represents a pulmonary-type adenocarcinoma. To our knowledge, only 3 case reports exist in the literature of a possible pulmonary (bronchial)–type adenocarcinoma arising in a dermoid cyst [6-8]. All were considered to arise from ciliated respiratory-type epithelium
but none were stained with pulmonary markers (TTF1, PE10, napsin A) to help confirm a pulmonary-type adenocarcinoma. A case of squamous carcinoma arising from bronchial epithelium in an ovarian dermoid cyst has also been reported [22]. The latter case raises the interesting possibility that some squamous carcinomas arising in dermoid cysts are derived from bronchial tissue rather than the more commonly accepted pathway of development from areas of epidermis [22]. Molecular studies revealed no evidence of EGFR mutation. Activating EGFR mutations are present in approximately 10% of pulmonary non–small cell carcinomas in white patients with a higher rate in adenocarcinomas occurring in nonsmokers [23]. Mutations are present within exons 18 to 21 of EGFR. Deletions in exon 19 and the missense mutation L858R in exon 21 represent 90% of all the alterations seen in human tumors and convey good response to tyrosine kinase inhibitors; gefitinib has been licensed in mutated tumors as a first-line monotherapy. Although metastasis of lung carcinoma to the ovary is uncommon, a pulmonary-type adenocarcinoma within the ovary is much more likely to represent a metastatic than a primary neoplasm [24], and it is important in such cases to review the clinical information and radiological features to ensure that a primary lung lesion is not missed. In our case,
2092 there was no history or clinical features to suggest a primary pulmonary lesion. Moreover the presence of a dermoid cyst and in particular the close association of the pulmonary-type adenocarcinoma to a bronchial structure were in keeping with a primary pulmonary-type adenocarcinoma arising within a teratomatous neoplasm. General pathological features suggestive of a metastasis, such as bilateral ovarian involvement, a nodular pattern, and lymphovascular invasion, were also absent. In summary, we report a unique case where 2 separate malignancies arose within a dermoid cyst, one a signet ring mucinous adenocarcinoma and the other a pulmonarytype adenocarcinoma.
References [1] Pins MR, Young RH, Daly WJ, Scully RE. Primary squamous cell carcinoma of the ovary. Report of 37 cases. Am J Surg Pathol 1996;20: 823-33. [2] Hurwitz J, Fenton A, McCluggage WG, McKenna S. Squamous cell carcinoma of the ovary arising in a dermoid cyst: a case series. Br J Obstet Gynaecol 2007;114:1283-7. [3] Ronnett BM, Seidman JD. Mucinous tumors arising in ovarian mature cystic teratomas: relationship to the clinical syndrome of pseudomyxoma peritonei. Am J Surg Pathol 2003;27:650-7. [4] Vang R, Gown AM, Zhao C, et al. Ovarian mucinous tumors associated with mature cystic teratomas: morphologic and immunohistochemical analysis identifies a subset of potential teratomatous origin that shares features of lower gastrointestinal tract mucinous tumors more commonly encountered as secondary tumors in the ovary. Am J Surg Pathol 2007;31:854-69. [5] McKenney JK, Soslow RA, Longacre TA. Ovarian mature teratomas with mucinous epithelial neoplasms: morphologic heterogeneity and association with pseudomyxoma peritonei. Am J Surg Pathol 2008;32: 645-55. [6] Cobellis L, Schurfeld K, Ignacchiti E, et al. An ovarian mucinous adenocarcinoma arising from mature cystic teratoma associated with respiratory type tissue: a case report. Tumori 2004;90:521-4. [7] Yahata T, Kawasaki T, Serikawa T, et al. Adenocarcinoma arising from respiratory ciliated epithelium in benign cystic teratoma of the ovary: a case report with analyzes of the CT, MRI and pathological findings. J Obstet Gynaecol Res 2008;34:408-12. [8] Sumi T, Ishiko O, Maeda K, et al. Adenocarcinoma arising from respiratory ciliated epithelium in mature ovarian cystic teratoma. Arch Gynecol Obstet 2002;267:107-9.
C. Boyd et al. [9] O'Gorman T, Olaitan A. Primary malignant melanoma arising in an ovarian cystic teratoma. Eur J Gynaecol Oncol 2009;30:88-9. [10] McCluggage WG, Bissonette JP, Young RH. Primary malignant melanoma of the ovary: a report of 9 definite or probable cases with emphasis on their morphologic diversity and mimicry of other primary and secondary ovarian neoplasms. Int J Gynecol Pathol 2006;25:321-9. [11] Gupta D, Deavers MT, Silva EG, Malpica A. Malignant melanoma involving the ovary: a clinicopathologic and immunohistochemical study of 23 cases. Am J Surg Pathol 2004;28-771-780. [12] Roth LM, Miller AW, Talerman A. Typical thyroid type carcinoma arising in struma ovarii: a report of four cases and review of the literature. Int J Gynecol Pathol 2008;27:496-506. [13] Devaney K, Synder R, Norris HJ, Tavassoli FA. Proliferative and histologically malignant struma ovarii: a clinicopathologic study of 54 cases. Int J Gynecol Pathol 1993;12:333-43. [14] Vartanian RK, McRae B, Hessler RB. Sebaceous carcinoma arising in a mature cystic teratoma of the ovary. Int J Gynecol Pathol 2002;21: 418-21. [15] Rabban JT, Lerwill MF, McCluggage WG, Grenert JP, Zaloudek CJ. Primary ovarian carcinoid tumors may express CDX2: a potential pitfall in distinction from metastatic intestinal carcinoid tumors involving the ovary. Int J Gynecol Pathol 2009;28:41-8. [16] Aygun B, Kimpo M, Lee T, et al. An adolescent with ovarían osteosarcoma arising in a cystic teratoma. J Pediatr Hematol Oncol 2003;25:410-3. [17] Halabi M, Oliva E, Mazal PR, et al. Prostatic tissues in mature cystic teratoma of the ovary: a report of four cases, including one with features of prostatic adenocarcinoma, and cytogenetic studies. Int J Gynecol Pathol 2002;21:261-7. [18] Yoon HK, Park SM, Joo JE. Combined microcystic adnexal carcinoma and squamous cell carcinoma arising in the ovarian cystic teratoma-a brief case report. J Korean Med Sci 1994;9:432-5. [19] Tyagi SP, Maheshwari V, Tyagi N, Tewari K. Double malignancy in a benign cystic teratoma of the ovary (a case report). Indian J Cancer 1993;30:140-2. [20] Kubba LA, McCluggage WG, Liu J, et al. Thyroid transcription factor1 expression in ovarian epithelial neoplasms. Mod Pathol 2008;21: 485-90. [21] Siami K, McCluggage WG, Ordonez NG, et al. Thyroid transcription factor-1 expression in endometrial and endocervical adenocarcinomas. Am J Surg Pathol 2007;31:1759-63. [22] Fox H. Bronchial carcinoma in an ovarian cystic teratoma (dermoid). J Clin Pathol 1965;18:164-6. [23] Cheng L, Alexander RE, MacLennan GT, et al. Molecular pathology of lung cancer: key to personalized medicine. Mod Pathol 2012;25: 347-69. [24] Irving JA, Young RH. Lung carcinoma metastatic to the ovary: a clinicopathologic study of 32 cases emphasizing their morphologic spectrum and problems in differential diagnosis. Am J Surg Pathol 2005;29:997-1006.
www.elsevier.com/locate/humpath
Case study
Pulmonary-type adenocarcinoma and signet ring mucinous adenocarcinoma arising in an ovarian dermoid cyst: report of a unique case Clinton Boyd FRCPath a , Kaushik Patel FRCPath b , Brendan O'Sullivan FRCPath c , Philippe Taniere FRCPath c , W. Glenn McCluggage FRCPath a,⁎ a
Department of Pathology, Belfast Health and Social Care Trust and Molecular Pathology Programme, Centre for Cancer Research and Cell Biology, Queens University Belfast, BT12 6BA Belfast, UK b Department of Pathology, Kingston Hospital, Surrey, KT2 Kingston, UK c Department of Pathology, University Hospital of Birmingham, B15 2TG Birmingham, UK Received 1 April 2012; accepted 29 May 2012
Keywords: Ovary; Dermoid cyst; Mucinous adenocarcinoma; Pulmonary adenocarcinoma
Summary Dermoid cysts are common benign ovarian germ cell neoplasms. Occasionally, one of the mature elements undergoes malignant transformation resulting in the formation of a somatic malignancy; most commonly this is squamous carcinoma. We report a unique case where 2 separate malignancies arose within a dermoid cyst, one a signet ring mucinous adenocarcinoma and the other a pulmonary-type adenocarcinoma. There have been only occasional earlier case reports of a possible pulmonary-type adenocarcinoma arising in a dermoid cyst. In the case we report, the pulmonary-type adenocarcinoma was closely associated with a bronchial structure and exhibited diffuse positive immunohistochemical staining with TTF1, PE10, and napsin A. Molecular studies revealed no evidence of epidermal growth factor receptor mutation, a molecular alteration which may be found in primary pulmonary adenocarcinoma. © 2012 Elsevier Inc. All rights reserved.
1. Introduction Dermoid cysts (mature cystic teratomas) are common ovarian germ cell neoplasms composed of an admixture of mature elements of multiple types. Uncommonly, one of the elements undergoes malignant transformation resulting in the formation of a somatic neoplasm. Most commonly, this is a squamous carcinoma [1,2]. Adenocarcinomas, especially of mucinous type, have also been reported in association ⁎ Corresponding author. E-mail address: [email protected] (W. G. McCluggage). 0046-8177/$ – see front matter © 2012 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.humpath.2012.05.027
with and arising from teratomas [3-5]. In this report, we describe a unique case where a signet ring mucinous adenocarcinoma and a pulmonary-type adenocarcinoma both arose within a dermoid cyst; as far as we are aware, there have been only 3 earlier case reports of a possible pulmonary-type adenocarcinoma arising in an ovarian teratoma [6-8].
2. Case report A 35-year-old woman presented with pain in the left side of her vagina. Her past medical history included recurrent
Pulmonary-type and signet ring mucinous adenocarcinoma
2089
Fig. 1 Large intestinal mucosa (A), benign mucinous glands (B), and signet ring mucinous adenocarcinoma (C); the latter is diffusely positive with CK20 (D).
miscarriages and antiphospholipid syndrome. She had underwent bilateral ovarian cystectomies 10 years previously, and histology of both ovaries had shown dermoid cysts (it was not possible to review the slides of these). Following this, she was followed up by ultrasound scans and discharged after 3 years. An ultrasound scan before her latest admission showed an unremarkable anteverted uterus and a cystic right ovary measuring 52 × 20 × 41 mm. The left ovary measured 40 × 20 × 30 mm and contained several small cysts. She underwent laparoscopy which confirmed bilateral ovarian cysts. A right ovarian cystectomy with preservation of ovarian tissue and left oophorectomy was performed with the presumptive diagnosis of recurrent bilateral dermoid cysts.
3. Pathological findings The left ovary measured 38 × 25 × 25 mm. Sectioning revealed a unilocular cyst containing hair and sebaceous material. The right ovary was received as multiple pieces of tissue, the largest measuring 85 mm in maximum dimension. These were partly cystic and partly solid.
Histology of the left ovary showed features of a dermoid cyst (mature cystic teratoma). Elements present were skin with underlying skin appendage structures and adipose tissue. There were no immature or malignant elements. Multiple sections from the right ovary were examined histologically. They showed a residual dermoid cyst with skin and underlying skin appendage structures. Large intestinal-type mucosa was also present (Fig. 1A). In addition, many of the sections showed a mucinous neoplasm with a variable histological appearance. There were benign cysts and glands lined by a single layer of bland mucinous epithelium, areas of epithelial proliferation involving the lining of cysts, in keeping with borderline mucinous tumor of intestinal type, and foci of invasive adenocarcinoma. In areas, the adenocarcinoma was composed of well formed glands but there were also elements of signet ring adenocarcinoma. The features were those of an intestinal (enteric)–type mucinous tumor with benign, borderline and malignant elements. Fig. 1B and C illustrate representative areas of the mucinous neoplasm. The malignant mucinous elements, including the signet ring cells, were diffusely positive with cytokeratin 20 (CK20) (Fig. 1D), CEA, CDX2, and CA19.9. CK7 was only very focally positive in the
2090 malignant component, although the benign and borderline mucinous elements were diffusely positive. Estrogen receptor (ER), CA125, and PAX8 were negative in the mucinous elements. In addition to the mucinous elements, a morphologically distinct tumor was present. This comprised an adenocarcinoma with infiltrative glandular structures and solid arrangements of cells with no intracytoplasmic mucin. The cells contained moderately atypical nuclei with prominent nucleoli and a scant to moderate amount of eosinophilic cytoplasm (Fig. 2A). This adenocarcinoma was intimately related to and appeared to be arising from a bronchial structure lined by ciliated epithelium with extensive squamous metaplasia (Fig. 2B). In some areas, the 2 types of adenocarcinoma were intermingled, but for the most part, they were separate and they were clearly morphologically distinct. The nonmucinous adenocarcinoma exhibited diffuse CK7 positivity and was negative for CK20, CEA, CDX2, CA19.9, CA125, PAX8, and ER. There was diffuse positive nuclear staining with TTF1. Napsin A and PE10 were also diffusely positive. The immunohistochemical features were in keeping with a pulmonary-type adenocarcinoma. Fig. 3 illustrates various immunohistochemical stains within the pulmonary-type adenocarcinoma component.
4. Molecular analysis and findings A representative paraffin block containing the pulmonary type adenocarcinoma was tested for epidermal growth factor receptor (EGFR) mutations. The paraffin block was sectioned under sterile laboratory conditions. A single 3μm section was stained to allow assessment of appropriate tumor-rich areas suitable for DNA extraction. DNA extraction was performed using the Qiagen QIAmp FFPE Tissue Kit; a single 6-μm section was digested overnight. Mutation analysis was performed using the Qiagen Ther-
C. Boyd et al. ascreen kit. The EGFR analysis detects mutations in regions of exons 18, 19, 20, and 21 of the EGFR1 gene (known to contain clinically relevant mutations associated with drug sensitivity). EGFR was wild type with no pathogenic mutations found.
5. Discussion Dermoid cysts (mature cystic teratomas) are common ovarian neoplasms, particularly in women of reproductive age, and are by a significant margin the most common type of ovarian germ cell tumor. A wide range of tissues derived from all 3 germ cell layers may be present but some tissue types are found more commonly than others. Skin, skin appendage structures, smooth muscle, and adipose tissue are among the most commonly identified elements. Glial tissue, choroid plexus, nerves, gastrointestinal and bronchial tissue, thyroid, cartilage, and bone are less frequent but still relatively common. Any of the mature tissue components within a dermoid cyst can in theory undergo malignant transformation. Malignant transformation is rare, probably occurring in less than 1% of these neoplasms and by far the most frequent somatic malignancy to develop within these tumors is squamous cell carcinoma, which accounts for approximately 75% of cases of malignant transformation [1,2] Less common tumor types include adenocarcinoma, undifferentiated carcinoma, sebaceous carcinoma, thyroid-type tumors, carcinoid tumor, various sarcomas, glial neoplasms, and malignant melanoma [9-16]. Most adenocarcinomas are of intestinal mucinous type, sometimes with associated benign and borderline elements (the full range of mucinous neoplasms from benign to borderline to malignant can arise in association with a dermoid cyst), but more uncommon variants of adenocarcinoma reported include a single case of a prostatic-type adenocarcinoma [17]. Reports
Fig. 2 Pulmonary type adenocarcinoma composed of glandular and solid arrangements of cells (A). A bronchial-type structure is present lined by respiratory epithelium exhibiting squamous metaplasia (B).
Pulmonary-type and signet ring mucinous adenocarcinoma
Fig. 3
2091
The pulmonary-type adenocarcinoma is diffusely positive for CK7 (A), TTF1 (B), PE10 (C), and napsin A (D).
of 2 separate malignancies arising in a dermoid cyst are exceedingly rare, although there has been 1 report of a squamous carcinoma and a microcystic adnexal carcinoma and another of a leiomyosarcoma and squamous cell carcinoma in situ [18,19]. In the case we report, the 2 adenocarcinoma components were focally intermingled but for the most part they were separate and were morphologically and immunophenotypically clearly distinct. One adenocarcinoma comprised an intestinal-type mucinous adenocarcinoma with signet ring cells and benign and borderline elements. The second adenocarcinoma was morphologically different and was intimately associated with and probably arose from a bronchial structure. This adenocarcinoma was diffusely positive with CK7 and also with TTF1, PE10, and napsin A. Although none of these antibodies is totally specific [20,21], they are all markers of primary pulmonary adenocarcinoma. Given the association with a bronchial structure and the diffuse immunoreactivity with the 3 pulmonary markers mentioned, it is clear that this component represents a pulmonary-type adenocarcinoma. To our knowledge, only 3 case reports exist in the literature of a possible pulmonary (bronchial)–type adenocarcinoma arising in a dermoid cyst [6-8]. All were considered to arise from ciliated respiratory-type epithelium
but none were stained with pulmonary markers (TTF1, PE10, napsin A) to help confirm a pulmonary-type adenocarcinoma. A case of squamous carcinoma arising from bronchial epithelium in an ovarian dermoid cyst has also been reported [22]. The latter case raises the interesting possibility that some squamous carcinomas arising in dermoid cysts are derived from bronchial tissue rather than the more commonly accepted pathway of development from areas of epidermis [22]. Molecular studies revealed no evidence of EGFR mutation. Activating EGFR mutations are present in approximately 10% of pulmonary non–small cell carcinomas in white patients with a higher rate in adenocarcinomas occurring in nonsmokers [23]. Mutations are present within exons 18 to 21 of EGFR. Deletions in exon 19 and the missense mutation L858R in exon 21 represent 90% of all the alterations seen in human tumors and convey good response to tyrosine kinase inhibitors; gefitinib has been licensed in mutated tumors as a first-line monotherapy. Although metastasis of lung carcinoma to the ovary is uncommon, a pulmonary-type adenocarcinoma within the ovary is much more likely to represent a metastatic than a primary neoplasm [24], and it is important in such cases to review the clinical information and radiological features to ensure that a primary lung lesion is not missed. In our case,
2092 there was no history or clinical features to suggest a primary pulmonary lesion. Moreover the presence of a dermoid cyst and in particular the close association of the pulmonary-type adenocarcinoma to a bronchial structure were in keeping with a primary pulmonary-type adenocarcinoma arising within a teratomatous neoplasm. General pathological features suggestive of a metastasis, such as bilateral ovarian involvement, a nodular pattern, and lymphovascular invasion, were also absent. In summary, we report a unique case where 2 separate malignancies arose within a dermoid cyst, one a signet ring mucinous adenocarcinoma and the other a pulmonarytype adenocarcinoma.
References [1] Pins MR, Young RH, Daly WJ, Scully RE. Primary squamous cell carcinoma of the ovary. Report of 37 cases. Am J Surg Pathol 1996;20: 823-33. [2] Hurwitz J, Fenton A, McCluggage WG, McKenna S. Squamous cell carcinoma of the ovary arising in a dermoid cyst: a case series. Br J Obstet Gynaecol 2007;114:1283-7. [3] Ronnett BM, Seidman JD. Mucinous tumors arising in ovarian mature cystic teratomas: relationship to the clinical syndrome of pseudomyxoma peritonei. Am J Surg Pathol 2003;27:650-7. [4] Vang R, Gown AM, Zhao C, et al. Ovarian mucinous tumors associated with mature cystic teratomas: morphologic and immunohistochemical analysis identifies a subset of potential teratomatous origin that shares features of lower gastrointestinal tract mucinous tumors more commonly encountered as secondary tumors in the ovary. Am J Surg Pathol 2007;31:854-69. [5] McKenney JK, Soslow RA, Longacre TA. Ovarian mature teratomas with mucinous epithelial neoplasms: morphologic heterogeneity and association with pseudomyxoma peritonei. Am J Surg Pathol 2008;32: 645-55. [6] Cobellis L, Schurfeld K, Ignacchiti E, et al. An ovarian mucinous adenocarcinoma arising from mature cystic teratoma associated with respiratory type tissue: a case report. Tumori 2004;90:521-4. [7] Yahata T, Kawasaki T, Serikawa T, et al. Adenocarcinoma arising from respiratory ciliated epithelium in benign cystic teratoma of the ovary: a case report with analyzes of the CT, MRI and pathological findings. J Obstet Gynaecol Res 2008;34:408-12. [8] Sumi T, Ishiko O, Maeda K, et al. Adenocarcinoma arising from respiratory ciliated epithelium in mature ovarian cystic teratoma. Arch Gynecol Obstet 2002;267:107-9.
C. Boyd et al. [9] O'Gorman T, Olaitan A. Primary malignant melanoma arising in an ovarian cystic teratoma. Eur J Gynaecol Oncol 2009;30:88-9. [10] McCluggage WG, Bissonette JP, Young RH. Primary malignant melanoma of the ovary: a report of 9 definite or probable cases with emphasis on their morphologic diversity and mimicry of other primary and secondary ovarian neoplasms. Int J Gynecol Pathol 2006;25:321-9. [11] Gupta D, Deavers MT, Silva EG, Malpica A. Malignant melanoma involving the ovary: a clinicopathologic and immunohistochemical study of 23 cases. Am J Surg Pathol 2004;28-771-780. [12] Roth LM, Miller AW, Talerman A. Typical thyroid type carcinoma arising in struma ovarii: a report of four cases and review of the literature. Int J Gynecol Pathol 2008;27:496-506. [13] Devaney K, Synder R, Norris HJ, Tavassoli FA. Proliferative and histologically malignant struma ovarii: a clinicopathologic study of 54 cases. Int J Gynecol Pathol 1993;12:333-43. [14] Vartanian RK, McRae B, Hessler RB. Sebaceous carcinoma arising in a mature cystic teratoma of the ovary. Int J Gynecol Pathol 2002;21: 418-21. [15] Rabban JT, Lerwill MF, McCluggage WG, Grenert JP, Zaloudek CJ. Primary ovarian carcinoid tumors may express CDX2: a potential pitfall in distinction from metastatic intestinal carcinoid tumors involving the ovary. Int J Gynecol Pathol 2009;28:41-8. [16] Aygun B, Kimpo M, Lee T, et al. An adolescent with ovarían osteosarcoma arising in a cystic teratoma. J Pediatr Hematol Oncol 2003;25:410-3. [17] Halabi M, Oliva E, Mazal PR, et al. Prostatic tissues in mature cystic teratoma of the ovary: a report of four cases, including one with features of prostatic adenocarcinoma, and cytogenetic studies. Int J Gynecol Pathol 2002;21:261-7. [18] Yoon HK, Park SM, Joo JE. Combined microcystic adnexal carcinoma and squamous cell carcinoma arising in the ovarian cystic teratoma-a brief case report. J Korean Med Sci 1994;9:432-5. [19] Tyagi SP, Maheshwari V, Tyagi N, Tewari K. Double malignancy in a benign cystic teratoma of the ovary (a case report). Indian J Cancer 1993;30:140-2. [20] Kubba LA, McCluggage WG, Liu J, et al. Thyroid transcription factor1 expression in ovarian epithelial neoplasms. Mod Pathol 2008;21: 485-90. [21] Siami K, McCluggage WG, Ordonez NG, et al. Thyroid transcription factor-1 expression in endometrial and endocervical adenocarcinomas. Am J Surg Pathol 2007;31:1759-63. [22] Fox H. Bronchial carcinoma in an ovarian cystic teratoma (dermoid). J Clin Pathol 1965;18:164-6. [23] Cheng L, Alexander RE, MacLennan GT, et al. Molecular pathology of lung cancer: key to personalized medicine. Mod Pathol 2012;25: 347-69. [24] Irving JA, Young RH. Lung carcinoma metastatic to the ovary: a clinicopathologic study of 32 cases emphasizing their morphologic spectrum and problems in differential diagnosis. Am J Surg Pathol 2005;29:997-1006.