- Email: [email protected]
Appendiceal mixed endocrine-exocrine neoplasm presenting as bilateral solid tubular and classical Krukenberg tumour
CORRESPONDENCE
169
Appendiceal mixed endocrine–exocrine neoplasm presenting as bilateral solid tubular and classical Krukenberg tumour Sir, Krukenberg tumours (KTs) are fatal and almost always metastatic from gastric adenocarcinoma. The well known Krukenberg type is the classical or conventional KT (CKT) which is applied to any metastatic signet-ring cell adenocarcinoma.1 A less recognised type characterised by a predominant tubular pattern is called solid tubular Krukenberg tumour (STKT). 2 Appendiceal neuroendocrine tumours (NETs), most of which are mixed endocrine– exocrine neoplasms (MEENs), metastasise uncommonly as bilateral ovarian CKT or STKT.2–6 We report two metastatic MEENs presenting as bilateral STKT and CKT, and review the literature. Case 1 was a 42-year-old woman who presented with bilateral pelvic masses. On laparotomy, enlarged, solid ovaries and tumour deposits within the pelvic cavity were found. The patient underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy, appendicectomy, omentectomy, external iliac lymphadenectomy and biopsy of the peritoneal and sigmoid nodules. The right ovary measured 96676651 mm; the left measured 130690680 mm. On sectioning, the enlarged, bosselated ovaries were solid, grey, and contained scattered cysts and necrotic foci (Fig. 1A). The cysts measured from 5 to 18 mm across and contained clear, watery fluid. The appendix, which measured 46 mm in length and up to 10 mm in diameter, was indurated. Tumour nodules measuring from 5 to 28 mm across from the omentum, peritoneum and serosa of the uterus and sigmoid, as well as two left external iliac lymph nodes were submitted for histology. Three small tissue fragments were taken from the left ovary for ultrastructural studies. Microscopically, an ill-defined tumour composed predominantly of small solid tight clusters and nests, as well as clumps and cords of neoplastic cells diffusely infiltrated the appendix, mesoappendix and serosa. The mucosa and proximal surgical margin were not involved. Most of the cells showed a goblet cell or signet-ring-like morphology with a small, compressed eccentric nucleus and abundant intracytoplasmic mucin. Fused neoplastic glands and single-file atypical cells occupied less than 50% of the tumour and did not qualify as carcinomatous growth pattern. Scattered pools of extracellular mucin containing nests of goblet cells (Fig. 1B) and lymphatic, perineural and intraneural invasion were present. The stroma varied from loose and oedematous to dense fibrous or hyalinised. The intracellular and extracellular mucin was positive for periodic acid-Schiff with diastase (PASD) and mucicarmine. Immunohistochemically, the neoplastic cells were
170
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Pathology (2007), 39(1), February
immunoprofile of which was identical to the appendiceal GCC (Fig. 1D). The nodules from the omentum, peritoneum, uterine serosa and sigmoid nodule showed similar lesional cells. The two lymph nodes were positive for metastasis. Ultrastructurally, there were adherent cells with desmosomes between them. The nuclei were mostly round. Lumens, which were focally lined by microvilli, and paranuclear aggregates of filamentous material were seen. Intracytoplasmic mucin-containing vacuoles and scattered dense-core neurosecretory granules, as well as pale, rounded granules were present. There were some mucinsecreting vacuoles spilling their contents into the lumens (Fig. 2). Following surgery, the patient received chemotherapy. She died 17 months later. Post-mortem examination was not performed. Case 2 was a 42-year-old woman who presented with a right pelvic mass and intermenstrual bleeding for several months. The pelvic ultrasound revealed a pedunculated fibroid. On laparotomy, both ovaries were enlarged and solid. The appendix was indurated. Tumour deposits within the pelvic cavity were found. Externally, the stomach and the bowel appeared normal. The patient underwent bilateral oophorectomy, appendicectomy, left uterosacral biopsy and endometrial curettage. On gross examination, both ovaries were enlarged, grey, solid, and firm, with a bosselated surface. The right ovary measured 110690650 mm; the left measured 60640640 mm. The cut surfaces showed a solid pink central area surrounded by a tan, gelatinous rim of tissue with several small cystic spaces. The fallopian tubes were unremarkable. The indurated appendix measured 75 mm in length and up to 10 mm in diameter. Microscopically, a mixture of GCC and tubular carcinoid (TC) infiltrated the appendiceal wall (Fig. 3A). Some tubules contained inspissated mucus in their lumens. Carcinomatous growth pattern composed of moderately to poorly differentiated adenocarcinoma was seen in over 50% of the tumour. The tumour grew circumferentially
Fig. 1 Case 1. (A) The cut surface of the enlarged, bosselated ovaries showing scattered necrotic foci. (B) Goblet cell carcinoid infiltrates the appendiceal wall containing pools of extracellular mucin (H&E, 6200). (C) Classical Krukenberg’s tumour is characterised by signet-ring and goblet cells diffusely invading the fibrotic ovarian stroma (H&E, 6200). (D) Krukenberg’s tumour cells are immunoreactive for chromogranin A (ABC method, 6200).
positive for chromogranin A (polyclonal, 1:250; Dako, Denmark), synaptophysin (monoclonal, 1:500; Dako), neuron-specific enolase (NSE; polyclonal, 1:200; Dako), CAM 5.2 (monoclonal, 1:100; Becton Dickinson, USA) and carcinoembryonic antigen (CEA; monoclonal, 1:50, Dako). The findings were characteristic of goblet cell carcinoid (GCC). Similar tumour cells widely invaded the fibrotic ovaries, forming the so-called CKT (Fig. 1C), the
Fig. 2 Case 1. Ultrastructurally, microvilli focally lined a lumen (L). The nuclei (N) are rounded. The cytoplasm contains mucin-containing vacuoles (asterisk) and scattered dense-core neurosecretory granules (arrows). Desmosomes (arrowheads) are seen (EM, 66500).
CORRESPONDENCE
Fig. 3 Case 2. (A) Tubular carcinoid, with tubular growth pattern, diffusely infiltrates the appendiceal wall (H&E, 6200). Elsewhere, scattered goblet and signet ring cells are present. (B) Solid tubular variant of Krukenberg’s tumour is characterised by its predominant tubular pattern in the ovary (H&E, 6200). (C) Solid tubular Krukenberg’s tumour cells are positive for chromogranin (ABC method, 6200).
around the appendiceal lumen, involving almost the full length of the appendix but sparing the surgical margin. Both ovaries showed a diffuse infiltrate of tubular structures with occasional cells containing intracytoplasmic PASD-positive mucin, forming the so-called STKT (Fig. 3B). The appendiceal and ovarian tumour cells were immunoreactive for chromogranin A (Fig. 3C), synaptophysin, CAM 5.2 and CEA. The goblet cells were positive for NSE, but the tubules were negative. There was negative staining for inhibin alpha-subunit (monoclonal, 1:100; Oxford BioInnovation, UK) and serotonin (monoclonal, 1:20; Dako). The left uterosacral biopsy showed metastatic NET. The endometrial curettings contained proliferative glands. The patient received chemotherapy after surgery. She had tumour recurrence at the pouch of Douglas 33 months later and she died a further 27 months later. There was no autopsy.
171
Metastatic tumours involve the ovaries more often than any other site in the female genital tract.7 The mechanisms of spread are by lymphatic, transperitoneal and haematogenous dissemination. KTs account for 3–8% of all carcinomas metastatic to the ovaries.1 The source of a KT in over 70% of the cases is a gastric carcinoma. Indeed, most if not all ovarian metastases from the stomach are of the Krukenberg type.1 Carcinomas of the intestine, appendix, breast, gallbladder, biliary tract, pancreas, urinary bladder and cervix are the primary tumours in the remaining cases. KT is fatal and applies to any metastatic signet-ring cell adenocarcinoma whether or not the typical cellular stroma of the ovary is present.1,2,7 Ovarian metastases from appendiceal tumours are rare and may be seen in cases of NET, adenocarcinoma, and mucinous epithelial tumours of low-grade or borderline malignancy. The largest proportion of cases of tumours from the appendix to ovary is in the last category. With rare exceptions, NET is the only ovarian metastatic tumour that elicits stromal proliferation, which closely resembles an ovarian fibroma.1,8 NETs are the most common tumours of the appendix, yet there is little information on their aetiology and pathogenesis. Most NETs are incidental findings but they may be found associated with acute appendicitis as a result of obstruction of the lumen. The incidence of appendiceal NET ranges from 0.2 to 0.7%. NETs of the appendix are the least aggressive form of neuroendocrine neoplasms in the gastrointestinal tract, despite the fact that they are frequently transmural and may extend into the mesoappendix.9 Metastases from appendiceal NETs are rare and almost always localised in the liver and regional lymph nodes.1 Recently, appendiceal NETs were classified into welldifferentiated endocrine neoplasm (WDEN), also known as carcinoid, and mixed endocrine–exocrine neoplasms (MEEN). MEEN, which is subdivided into GCC, TC and mixed carcinoid-adenocarcinoma, possesses features of both carcinoid and adenocarcinoma, and poses difficulties in classification and prediction of clinical behaviour.10 GCC, the most recently described variant, and TC, the least aggressive of all MEENs,9 are encountered almost exclusively in the appendix.10 To the best of our knowledge, only 13 cases of metastatic appendiceal adenocarcinoids (also known as goblet cell carcinoid, mucinous carcinoid, mucocarcinoid, crypt cell carcinoma, amphicrine carcinoma and microglandular carcinoma) presenting as bilateral CKTs,2–6 and one case of unilateral KT,11 have been reported. The recent World Health Organization (WHO) classification suggests it is best to avoid the use of adenocarcinoid because it has been used for both GCC and TC and could cause confusion between these two lesions, which have different prognoses.9,10 STKT is distinct from the CKT because it displays a predominant tubular pattern. STKT constitutes approximately 20% of all KTs and may represent a better differentiated group.1 As far as we know, only one case of STKT metastatic from an appendiceal NET has been reported in the literature.2 KTs must be distinguished from primary and other metastatic ovarian tumours. Ovarian clear cell carcinoma may mimic CKT because it contains signet-ring-like cells but these are filled with non-mucinous material. Primary
172
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ovarian KTs have been reported; the clinical criteria for their diagnosis include survival for at least 5 years after surgical treatment and the exclusion of any other primary tumours.1,12 It is possible that some cases of primary ovarian KT may have been examples of primary ovarian GCCs. Metastatic GCC macroscopically resembles ovarian fibroma–thecoma and Brenner’s tumours. These tumours do not contain goblet cells or signet ring cells. The STKT can be confused with a Sertoli–Leydig cell tumour but the latter does not contain PASD and mucicarmine-positive mucin-filled cells.1,8,12 The greatest challenge pathologically is separation of metastatic from primary ovarian NET. Metastatic GCCs are microscopically identical to primary ovarian GCCs but the former are not associated with other teratomatous element, are usually bilateral and multifocal, and extraovarian carcinoid is present.1,8 Accurate data on prognosis and treatment of metastatic appendiceal MEENs presenting as bilateral CKT and STKT are lacking because of their rarity.13 The treatment of the previously reported 13 cases of metastatic MEEN included surgery (appendicectomy, right colectomy, total abdominal hysterectomy and bilateral salpingo-oophorectomy, omentectomy, pelvic lymphadenectomy) with or without chemotherapy or radiotherapy.5,11 Four of these patients died 12–13 months after diagnosis.11 A recent report stated that there was no known effective treatment for disseminated MEENs.13 In the present study, the two patients received chemotherapy after surgery. The patient with CKT died 17 months after treatment. The patient with STKT had tumour recurrence at the pouch of Douglas 33 months after treatment and died a further 27 months later. There is a need to collect more cases of appendiceal MEENs with ovarian metastases presenting as KT because the optimal treatment is still unknown. Leonardo D. Santos Alan Kennerson Murray Killingsworth Department of Anatomical Pathology, South Western Area Pathology Service, Liverpool, New South Wales, Australia Contact Dr L. D. Santos. Email: [email protected] 1. Russell P, Farnsworth A. Surgical Pathology of the Ovaries. 2nd ed, New York: Churchill Livingstone, 1997; 554–60, 597–603, 609–22. 2. Bullon A, Arseneau J, Prat J, Young RH, Scully RE. Tubular Krukenberg tumor. A problem in histopathologic diagnosis. Am J Surg Pathol 1981; 5: 225–32. 3. Thomas R, Barnhill D, Worsham F, Hoskins W. Krukenberg tumor of the ovary from an occult appendiceal primary: Case report and literature review. Obstet Gynecol 1985; 65: 95–8S. 4. Hirschfield LS, Kahn LB, Winkler B, Bochner RZ, Gibstein AA. Adenocarcinoid of the appendix presenting as bilateral Krukenberg’s tumor of the ovaries. Immunohistochemical and ultrastructural studies and literature review. Arch Pathol Lab Med 1985; 109: 930–3. 5. Hood IC, Jones BA, Watts JC. Mucinous carcinoid tumor of the appendix presenting as bilateral ovarian tumors. Arch Pathol Lab Med 1986; 110: 336–40. 6. Klein EA, Rosen MH. Bilateral Krukenberg tumors due to appendiceal mucinous carcinoid. Int J Gynecol Pathol 1996; 15: 85–8. 7. Mazur MT, Hsueh S, Gersell DJ. Metastases to the female genital tract. Analyses of 325 cases. Cancer 1984; 53: 1978–84.
Pathology (2007), 39(1), February
8. Tavassoli FA, Devilee P. World Health Organization Classification of Tumours. Pathology and Genetics of Tumours of the Breast and Female Genital Organs. Lyon: IARC Press, 2003; 193–6. 9. Carr NJ, Sobin LH. Neuroendocrine tumors of the appendix. Semin Diagn Pathol 2004; 21: 108–19. 10. Capella C, Solcia E, Sobin LH. Endocrine tumours of the appendix. In: Hamilton SR, Aaltonen LA, editors. World Health Organization Classification of Tumours. Pathology and Genetics of Tumours of the Digestive System. Lyon: IARC Press, 2000; 279–323. 11. Miller RT, Sarikaya H, Jenison EL. Adenocarcinoid tumor of the appendix presenting as unilateral Krukenberg tumor. J Surg Oncol 1988; 37: 65–71. 12. Holtz F, Hart WR. Krukenberg tumors of the ovary. A clinicopathologic analysis of 27 cases. Cancer 1982; 50: 2438–47. 13. Chen KTK. Case Report: Appendiceal adenocarcinoid with ovarian metastasis. Gynecol Oncol 1990; 38: 286–8.
DOI: 10.1080/00313020601123862
169
Appendiceal mixed endocrine–exocrine neoplasm presenting as bilateral solid tubular and classical Krukenberg tumour Sir, Krukenberg tumours (KTs) are fatal and almost always metastatic from gastric adenocarcinoma. The well known Krukenberg type is the classical or conventional KT (CKT) which is applied to any metastatic signet-ring cell adenocarcinoma.1 A less recognised type characterised by a predominant tubular pattern is called solid tubular Krukenberg tumour (STKT). 2 Appendiceal neuroendocrine tumours (NETs), most of which are mixed endocrine– exocrine neoplasms (MEENs), metastasise uncommonly as bilateral ovarian CKT or STKT.2–6 We report two metastatic MEENs presenting as bilateral STKT and CKT, and review the literature. Case 1 was a 42-year-old woman who presented with bilateral pelvic masses. On laparotomy, enlarged, solid ovaries and tumour deposits within the pelvic cavity were found. The patient underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy, appendicectomy, omentectomy, external iliac lymphadenectomy and biopsy of the peritoneal and sigmoid nodules. The right ovary measured 96676651 mm; the left measured 130690680 mm. On sectioning, the enlarged, bosselated ovaries were solid, grey, and contained scattered cysts and necrotic foci (Fig. 1A). The cysts measured from 5 to 18 mm across and contained clear, watery fluid. The appendix, which measured 46 mm in length and up to 10 mm in diameter, was indurated. Tumour nodules measuring from 5 to 28 mm across from the omentum, peritoneum and serosa of the uterus and sigmoid, as well as two left external iliac lymph nodes were submitted for histology. Three small tissue fragments were taken from the left ovary for ultrastructural studies. Microscopically, an ill-defined tumour composed predominantly of small solid tight clusters and nests, as well as clumps and cords of neoplastic cells diffusely infiltrated the appendix, mesoappendix and serosa. The mucosa and proximal surgical margin were not involved. Most of the cells showed a goblet cell or signet-ring-like morphology with a small, compressed eccentric nucleus and abundant intracytoplasmic mucin. Fused neoplastic glands and single-file atypical cells occupied less than 50% of the tumour and did not qualify as carcinomatous growth pattern. Scattered pools of extracellular mucin containing nests of goblet cells (Fig. 1B) and lymphatic, perineural and intraneural invasion were present. The stroma varied from loose and oedematous to dense fibrous or hyalinised. The intracellular and extracellular mucin was positive for periodic acid-Schiff with diastase (PASD) and mucicarmine. Immunohistochemically, the neoplastic cells were
170
CORRESPONDENCE
Pathology (2007), 39(1), February
immunoprofile of which was identical to the appendiceal GCC (Fig. 1D). The nodules from the omentum, peritoneum, uterine serosa and sigmoid nodule showed similar lesional cells. The two lymph nodes were positive for metastasis. Ultrastructurally, there were adherent cells with desmosomes between them. The nuclei were mostly round. Lumens, which were focally lined by microvilli, and paranuclear aggregates of filamentous material were seen. Intracytoplasmic mucin-containing vacuoles and scattered dense-core neurosecretory granules, as well as pale, rounded granules were present. There were some mucinsecreting vacuoles spilling their contents into the lumens (Fig. 2). Following surgery, the patient received chemotherapy. She died 17 months later. Post-mortem examination was not performed. Case 2 was a 42-year-old woman who presented with a right pelvic mass and intermenstrual bleeding for several months. The pelvic ultrasound revealed a pedunculated fibroid. On laparotomy, both ovaries were enlarged and solid. The appendix was indurated. Tumour deposits within the pelvic cavity were found. Externally, the stomach and the bowel appeared normal. The patient underwent bilateral oophorectomy, appendicectomy, left uterosacral biopsy and endometrial curettage. On gross examination, both ovaries were enlarged, grey, solid, and firm, with a bosselated surface. The right ovary measured 110690650 mm; the left measured 60640640 mm. The cut surfaces showed a solid pink central area surrounded by a tan, gelatinous rim of tissue with several small cystic spaces. The fallopian tubes were unremarkable. The indurated appendix measured 75 mm in length and up to 10 mm in diameter. Microscopically, a mixture of GCC and tubular carcinoid (TC) infiltrated the appendiceal wall (Fig. 3A). Some tubules contained inspissated mucus in their lumens. Carcinomatous growth pattern composed of moderately to poorly differentiated adenocarcinoma was seen in over 50% of the tumour. The tumour grew circumferentially
Fig. 1 Case 1. (A) The cut surface of the enlarged, bosselated ovaries showing scattered necrotic foci. (B) Goblet cell carcinoid infiltrates the appendiceal wall containing pools of extracellular mucin (H&E, 6200). (C) Classical Krukenberg’s tumour is characterised by signet-ring and goblet cells diffusely invading the fibrotic ovarian stroma (H&E, 6200). (D) Krukenberg’s tumour cells are immunoreactive for chromogranin A (ABC method, 6200).
positive for chromogranin A (polyclonal, 1:250; Dako, Denmark), synaptophysin (monoclonal, 1:500; Dako), neuron-specific enolase (NSE; polyclonal, 1:200; Dako), CAM 5.2 (monoclonal, 1:100; Becton Dickinson, USA) and carcinoembryonic antigen (CEA; monoclonal, 1:50, Dako). The findings were characteristic of goblet cell carcinoid (GCC). Similar tumour cells widely invaded the fibrotic ovaries, forming the so-called CKT (Fig. 1C), the
Fig. 2 Case 1. Ultrastructurally, microvilli focally lined a lumen (L). The nuclei (N) are rounded. The cytoplasm contains mucin-containing vacuoles (asterisk) and scattered dense-core neurosecretory granules (arrows). Desmosomes (arrowheads) are seen (EM, 66500).
CORRESPONDENCE
Fig. 3 Case 2. (A) Tubular carcinoid, with tubular growth pattern, diffusely infiltrates the appendiceal wall (H&E, 6200). Elsewhere, scattered goblet and signet ring cells are present. (B) Solid tubular variant of Krukenberg’s tumour is characterised by its predominant tubular pattern in the ovary (H&E, 6200). (C) Solid tubular Krukenberg’s tumour cells are positive for chromogranin (ABC method, 6200).
around the appendiceal lumen, involving almost the full length of the appendix but sparing the surgical margin. Both ovaries showed a diffuse infiltrate of tubular structures with occasional cells containing intracytoplasmic PASD-positive mucin, forming the so-called STKT (Fig. 3B). The appendiceal and ovarian tumour cells were immunoreactive for chromogranin A (Fig. 3C), synaptophysin, CAM 5.2 and CEA. The goblet cells were positive for NSE, but the tubules were negative. There was negative staining for inhibin alpha-subunit (monoclonal, 1:100; Oxford BioInnovation, UK) and serotonin (monoclonal, 1:20; Dako). The left uterosacral biopsy showed metastatic NET. The endometrial curettings contained proliferative glands. The patient received chemotherapy after surgery. She had tumour recurrence at the pouch of Douglas 33 months later and she died a further 27 months later. There was no autopsy.
171
Metastatic tumours involve the ovaries more often than any other site in the female genital tract.7 The mechanisms of spread are by lymphatic, transperitoneal and haematogenous dissemination. KTs account for 3–8% of all carcinomas metastatic to the ovaries.1 The source of a KT in over 70% of the cases is a gastric carcinoma. Indeed, most if not all ovarian metastases from the stomach are of the Krukenberg type.1 Carcinomas of the intestine, appendix, breast, gallbladder, biliary tract, pancreas, urinary bladder and cervix are the primary tumours in the remaining cases. KT is fatal and applies to any metastatic signet-ring cell adenocarcinoma whether or not the typical cellular stroma of the ovary is present.1,2,7 Ovarian metastases from appendiceal tumours are rare and may be seen in cases of NET, adenocarcinoma, and mucinous epithelial tumours of low-grade or borderline malignancy. The largest proportion of cases of tumours from the appendix to ovary is in the last category. With rare exceptions, NET is the only ovarian metastatic tumour that elicits stromal proliferation, which closely resembles an ovarian fibroma.1,8 NETs are the most common tumours of the appendix, yet there is little information on their aetiology and pathogenesis. Most NETs are incidental findings but they may be found associated with acute appendicitis as a result of obstruction of the lumen. The incidence of appendiceal NET ranges from 0.2 to 0.7%. NETs of the appendix are the least aggressive form of neuroendocrine neoplasms in the gastrointestinal tract, despite the fact that they are frequently transmural and may extend into the mesoappendix.9 Metastases from appendiceal NETs are rare and almost always localised in the liver and regional lymph nodes.1 Recently, appendiceal NETs were classified into welldifferentiated endocrine neoplasm (WDEN), also known as carcinoid, and mixed endocrine–exocrine neoplasms (MEEN). MEEN, which is subdivided into GCC, TC and mixed carcinoid-adenocarcinoma, possesses features of both carcinoid and adenocarcinoma, and poses difficulties in classification and prediction of clinical behaviour.10 GCC, the most recently described variant, and TC, the least aggressive of all MEENs,9 are encountered almost exclusively in the appendix.10 To the best of our knowledge, only 13 cases of metastatic appendiceal adenocarcinoids (also known as goblet cell carcinoid, mucinous carcinoid, mucocarcinoid, crypt cell carcinoma, amphicrine carcinoma and microglandular carcinoma) presenting as bilateral CKTs,2–6 and one case of unilateral KT,11 have been reported. The recent World Health Organization (WHO) classification suggests it is best to avoid the use of adenocarcinoid because it has been used for both GCC and TC and could cause confusion between these two lesions, which have different prognoses.9,10 STKT is distinct from the CKT because it displays a predominant tubular pattern. STKT constitutes approximately 20% of all KTs and may represent a better differentiated group.1 As far as we know, only one case of STKT metastatic from an appendiceal NET has been reported in the literature.2 KTs must be distinguished from primary and other metastatic ovarian tumours. Ovarian clear cell carcinoma may mimic CKT because it contains signet-ring-like cells but these are filled with non-mucinous material. Primary
172
CORRESPONDENCE
ovarian KTs have been reported; the clinical criteria for their diagnosis include survival for at least 5 years after surgical treatment and the exclusion of any other primary tumours.1,12 It is possible that some cases of primary ovarian KT may have been examples of primary ovarian GCCs. Metastatic GCC macroscopically resembles ovarian fibroma–thecoma and Brenner’s tumours. These tumours do not contain goblet cells or signet ring cells. The STKT can be confused with a Sertoli–Leydig cell tumour but the latter does not contain PASD and mucicarmine-positive mucin-filled cells.1,8,12 The greatest challenge pathologically is separation of metastatic from primary ovarian NET. Metastatic GCCs are microscopically identical to primary ovarian GCCs but the former are not associated with other teratomatous element, are usually bilateral and multifocal, and extraovarian carcinoid is present.1,8 Accurate data on prognosis and treatment of metastatic appendiceal MEENs presenting as bilateral CKT and STKT are lacking because of their rarity.13 The treatment of the previously reported 13 cases of metastatic MEEN included surgery (appendicectomy, right colectomy, total abdominal hysterectomy and bilateral salpingo-oophorectomy, omentectomy, pelvic lymphadenectomy) with or without chemotherapy or radiotherapy.5,11 Four of these patients died 12–13 months after diagnosis.11 A recent report stated that there was no known effective treatment for disseminated MEENs.13 In the present study, the two patients received chemotherapy after surgery. The patient with CKT died 17 months after treatment. The patient with STKT had tumour recurrence at the pouch of Douglas 33 months after treatment and died a further 27 months later. There is a need to collect more cases of appendiceal MEENs with ovarian metastases presenting as KT because the optimal treatment is still unknown. Leonardo D. Santos Alan Kennerson Murray Killingsworth Department of Anatomical Pathology, South Western Area Pathology Service, Liverpool, New South Wales, Australia Contact Dr L. D. Santos. Email: [email protected] 1. Russell P, Farnsworth A. Surgical Pathology of the Ovaries. 2nd ed, New York: Churchill Livingstone, 1997; 554–60, 597–603, 609–22. 2. Bullon A, Arseneau J, Prat J, Young RH, Scully RE. Tubular Krukenberg tumor. A problem in histopathologic diagnosis. Am J Surg Pathol 1981; 5: 225–32. 3. Thomas R, Barnhill D, Worsham F, Hoskins W. Krukenberg tumor of the ovary from an occult appendiceal primary: Case report and literature review. Obstet Gynecol 1985; 65: 95–8S. 4. Hirschfield LS, Kahn LB, Winkler B, Bochner RZ, Gibstein AA. Adenocarcinoid of the appendix presenting as bilateral Krukenberg’s tumor of the ovaries. Immunohistochemical and ultrastructural studies and literature review. Arch Pathol Lab Med 1985; 109: 930–3. 5. Hood IC, Jones BA, Watts JC. Mucinous carcinoid tumor of the appendix presenting as bilateral ovarian tumors. Arch Pathol Lab Med 1986; 110: 336–40. 6. Klein EA, Rosen MH. Bilateral Krukenberg tumors due to appendiceal mucinous carcinoid. Int J Gynecol Pathol 1996; 15: 85–8. 7. Mazur MT, Hsueh S, Gersell DJ. Metastases to the female genital tract. Analyses of 325 cases. Cancer 1984; 53: 1978–84.
Pathology (2007), 39(1), February
8. Tavassoli FA, Devilee P. World Health Organization Classification of Tumours. Pathology and Genetics of Tumours of the Breast and Female Genital Organs. Lyon: IARC Press, 2003; 193–6. 9. Carr NJ, Sobin LH. Neuroendocrine tumors of the appendix. Semin Diagn Pathol 2004; 21: 108–19. 10. Capella C, Solcia E, Sobin LH. Endocrine tumours of the appendix. In: Hamilton SR, Aaltonen LA, editors. World Health Organization Classification of Tumours. Pathology and Genetics of Tumours of the Digestive System. Lyon: IARC Press, 2000; 279–323. 11. Miller RT, Sarikaya H, Jenison EL. Adenocarcinoid tumor of the appendix presenting as unilateral Krukenberg tumor. J Surg Oncol 1988; 37: 65–71. 12. Holtz F, Hart WR. Krukenberg tumors of the ovary. A clinicopathologic analysis of 27 cases. Cancer 1982; 50: 2438–47. 13. Chen KTK. Case Report: Appendiceal adenocarcinoid with ovarian metastasis. Gynecol Oncol 1990; 38: 286–8.
DOI: 10.1080/00313020601123862