Composite cervical adenocarcinoma composed of adenoma malignum and gastric type adenocarcinoma (dedifferentiated adenoma malignum) in a patient with Peutz Jeghers syndrome

McCluggage, W. Glenn; Harley, Ian; Houghton, Joseph; Geyer, Felipe C.; Mackay, Alan; Reis‐Filho, Jorge S.

doi:10.1136/jcp.2010.080150

Cited by 32 publications

(27 citation statements)

References 43 publications

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“…Mccluggage et al reported composite carcinoma for the first time and identified common genetic aberrations between MDa and GTa indicating a possible link between these tumors. In their case, the MDa and GTa occupied discrete areas in the cervix (8). In contrast, the MDa and GTa components in the current case as well as the case reported by Peng et al were continuous in nature, and had similar immunophenotypes, favoring the hypothesis that GTa may arise from dedifferentiation of MDa (9).…”

Section: Discussioncontrasting

confidence: 53%

Synchronous cervical minimal deviation adenocarcinoma, gastric type adenocarcinoma and lobular endocervical glandular hyperplasia along with stil in peutz-jeghers syndrome: eliciting oncogenesis pathways

Neyaz¹,

Husain²,

Deodhar³

et al. 2013

TJPATH

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ABSTRACTwe describe an unusual case of a Peutz-Jeghers syndrome associated with a composite synchronous cervical neoplasia comprising precursor "lobular endocervical glandular hyperplasia (LEGH)", "minimal deviation adenocarcinoma (MDa)" and "gastric-type adenocarcinoma (GTa)" along with a serous tubal intraepithelial lesion (STIL) in the right fallopian tube. a 24-year-old woman presented with a white mucoid discharge and bleeding per vaginum for one year. Histopathological evaluation showed MDa & GTa in FIGo grade III with pelvic lymph node metastasis despite a deceptively bland tumour morphology and low ki-67 index, indicating an aggressive tumour course and poor prognosis. Diagnostic marker profile in the cervix showed gastric type mucin and positive expression of ck-7, ck-20 (patchy), cEa, and negative cDX-2, p16, ER and PR. Further an attempt at eliciting the oncogenesis pathway in view of the p16 and HPV negative nature of the gastric type cervical adenocarcinoma showed negativity for p53 but activation of cyclin D1. Growth factors including Her2 and EGFR were negative while VEGFR was over-expressed. She was treated by radical hysterectomy and pelvic radiation. She was free from recurrence at the 12-month follow-up. This is a first-time report of a STIL in the fallopian tube which was validated by a unilateral mutant type p53 expression and increased ki67 index, associated with synchronous gastric type adenocarcinoma of the cervix in all stages of evolution.

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Section: Discussioncontrasting

confidence: 53%

Synchronous cervical minimal deviation adenocarcinoma, gastric type adenocarcinoma and lobular endocervical glandular hyperplasia along with stil in peutz-jeghers syndrome: eliciting oncogenesis pathways

Neyaz¹,

Husain²,

Deodhar³

et al. 2013

TJPATH

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“…As discussed, they show a spectrum of differentiation including adenoma malignum as the well differentiated variant and gastric-type adenocarcinoma as the more poorly differentiated form (1–4). They are characterised morphologically by tumour cells with abundant clear or pale eosinophilic cytoplasm, sometimes with prominent cell membranes; in many cases, the tumour cells contain obvious intracytoplasmic mucin.…”

Section: Discussionmentioning

confidence: 99%

“…Adenocarcinomas exhibiting gastric differentiation represent an uncommon, but probably under-recognised, subtype of non-HPV related cervical adenocarcinoma (1–4). As discussed, they show a spectrum of differentiation including adenoma malignum as the well differentiated variant and gastric-type adenocarcinoma as the more poorly differentiated form (1–4).…”

Section: Discussionmentioning

confidence: 99%

“…These form a continuum from adenoma malignum (mucinous variant of minimal deviation adenocarcinoma), which is now regarded as the well differentiated end of the spectrum, to gastric-type adenocarcinoma which represents the more poorly differentiated variant. Adenoma malignum and gastric-type adenocarcinoma form part of a spectrum with overlapping morphologies (4); indeed, it is well known that more atypical foci may be present in adenoma malignum and the identification of such areas is one of the most useful features in distinguishing adenoma malignum from various benign endocervical glandular lesions. Therefore, there seems no point in separating adenoma malignum from gastric-type adenocarcinoma and it is recommended that the term gastric-type adenocarcinoma is used to encompass this spectrum of neoplasia (5).…”

Section: Introductionmentioning

confidence: 99%

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A Detailed Immunohistochemical Analysis of a Large Series of Cervical and Vaginal Gastric-type Adenocarcinomas

Carleton

Hoang

Sah

et al. 2016

American Journal of Surgical Pathology

131

156

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Adenocarcinomas exhibiting gastric differentiation represent a recently described and uncommon subtype of non-human papillomavirus (HPV) related cervical adenocarcinoma. They comprise a spectrum from a well differentiated variant (adenoma malignum/mucinous variant of minimal deviation adenocarcinoma) to a more poorly overtly malignant form, generally referred to as gastric-type adenocarcinoma. Rarely, such tumours have also been described as primary vaginal neoplasms. Gastric-type adenocarcinomas exhibit considerable morphological overlap with adenocarcinomas originating outside the female genital tract, especially mucinous adenocarcinomas arising in the pancreas and biliary tract. Moreover they often metastasize to unusual sites, such as the ovary and peritoneum/omentum, where they can be mistaken for metastatic adenocarcinomas from other, non-gynaecological sites. There is little information regarding the immunophenotype of gastric-type adenocarcinomas and knowledge of this is important to aid in the distinction from other adenocarcinomas. In this study, we undertook a detailed immunohistochemical analysis of a large series of cervical (n=45) and vaginal (n=2) gastric-type adenocarcinomas. Markers included were CK7, CK20, CDX2, CEA, CA125, CA19.9, p16, ER, PR, MUC6, PAX8, PAX2, p53, hepatocyte nuclear factor 1 beta (HNF1β), carbonic anhydrase IX (CAIX), HER2 and MMR proteins. All markers were classified as negative, focal (<50% of tumour cells positive) or diffuse (≥50% tumour cells positive) except for p53 (classified as “wild-type” or “mutation-type”), HER2 (scored using the College of American Pathologists guidelines for gastric carcinomas) and MMR proteins (categorised as retained or lost). There was positive staining with CK7 (47/47 – 45 diffuse, 2 focal), MUC6 (17/21 – 6 diffuse, 11 focal), CEA (25/31 – 12 diffuse, 13 focal), CAIX (20/24 – 8 diffuse, 12 focal), PAX8 (32/47 – 20 diffuse, 12 focal), CA125 (36/45 – 5 diffuse, 31 focal), CA19.9 (11/11 – 8 diffuse, 3 focal), HNF1β (13/14 – 12 diffuse, 1 focal), CDX2 (24/47 – 4 diffuse, 20 focal), CK20 (23/47 – 6 diffuse, 17 focal) and p16 (18/47 – 4 diffuse, 14 focal). Most cases were negative with ER (29/31), PR (10/11), PAX2 (18/19) and HER2 (25/26). p53 showed “wild-type” and ”mutation-type” staining in 27/46 and 19/46 cases respectively. MMR protein expression was retained in 19/20 cases with loss of MSH6 staining in one patient with Lynch syndrome. Molecular studies for HPV were undertaken in two tumours which exhibited diffuse” block-type” immunoreactivity with p16 and both were negative. This is the first detailed immunohistochemical study of a large series of gastric-type adenocarcinomas of the lower female genital tract. Our results indicate immunophenotypic overlap with pancreaticobiliary adenocarcinomas but suggest that PAX8 immunoreactivity may be especially useful in distinguishing gastric-type adenocarcinomas from pancreaticobiliary and other non-gynaecological adenocarcinomas which are usually negative. Diffuse “block-type”p16 immunoreactivity ...

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“…9,16,20 Histologic criteria for GAS were first defined by Kojima et al to include cells showing clear and/or pale eosinophilic and voluminous cytoplasm with distinct cell borders comprising the majority of the tumor. 16 In some cases benign endocervical glands showing ‘gastric metaplasia’ resembling normal pyloric glands of the antral stomach are found adjacent to invasive adenocarcinoma, and these tumors frequently contain areas that are indistinguishable from MDA.…”

Section: Introductionmentioning

confidence: 99%

Gastric-type Endocervical Adenocarcinoma

Karamurzin

Kiyokawa

Parkash

et al. 2015

American Journal of Surgical Pathology

201

119

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Gastric type adenocarcinoma of the uterine cervix (GAS) is a rare variant of mucinous endocervical adenocarcinoma not etiologically associated with human papillomavirus (HPV) infection, with minimal deviation adenocarcinoma (MDA) at the well-differentiated end of the morphologic spectrum. These tumors are reported to have worse prognosis than usual HPV-associated endocervical adenocarcinoma (UEA). A retrospective review of GAS was performed from the pathology databases of three institutions spanning 20 years. Stage, metastatic patterns, and overall survival were documented. Forty GAS cases were identified, with clinical follow-up data available for 38. The tumors were subclassified as MDA (n=13) and non-MDA GAS (n=27). Two patients were syndromic (one Li-Fraumeni, one Peutz-Jeghers). At presentation, 59% were advanced stage (FIGO II–IV), 50% had lymph node metastases, 35% had ovarian involvement, 20% had abdominal disease, 39% had at least one site of metastasis at the time of initial surgery, and 12% of patients experienced distant recurrence. The metastatic sites included lymph nodes, adnexa, omentum, bowel, peritoneum, diaphragm, abdominal wall, bladder, vagina, appendix, and brain. Follow-up ranged from 1.4 to 136.0 months (mean, 33.9 months); 20/38 (52.6%) had no evidence of disease, 3/38 (7.9%) were alive with disease, and 15/38 (39.5%) died of disease. Disease specific survival at 5 years was 42% for GAS vs. 91% for UEA. There were no survival differences between MDA and non-MDA GAS. GAS represents a distinct, biologically aggressive type of endocervical adenocarcinoma. The majority of patients present at advanced stage and pelvic, abdominal, and distant metastases are not uncommon.

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Composite cervical adenocarcinoma composed of adenoma malignum and gastric type adenocarcinoma (dedifferentiated adenoma malignum) in a patient with Peutz Jeghers syndrome

Cited by 32 publications

References 43 publications

Synchronous cervical minimal deviation adenocarcinoma, gastric type adenocarcinoma and lobular endocervical glandular hyperplasia along with stil in peutz-jeghers syndrome: eliciting oncogenesis pathways

Synchronous cervical minimal deviation adenocarcinoma, gastric type adenocarcinoma and lobular endocervical glandular hyperplasia along with stil in peutz-jeghers syndrome: eliciting oncogenesis pathways

A Detailed Immunohistochemical Analysis of a Large Series of Cervical and Vaginal Gastric-type Adenocarcinomas

Gastric-type Endocervical Adenocarcinoma

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