Best practice J Clin Pathol: first published as 10.1136/jclinpath-2017-204787 on 28 November 2017. Downloaded from Diagnostic immunohistochemistry in gynaecological neoplasia: a brief survey of the most common scenarios Elisabetta Kuhn,1,2,3 Ayse Ayhan4,5 1Pathology Unit, Arcispedale ABSTRact of gynaecological malignancies and enriched the Santa Maria Nuova–IRCCS, Immunohistochemistry is a valuable adjunct in routine portfolio of IHC markers useful in the differential Reggio Emilia, Italy 2 diagnosis of gynaecological diseases. Accordingly, Department of Morphology, gynaecological pathology. The molecular revolution Surgery and Experimental has redesigned knowledge of gynaecological cancers IHC represents a solid adjunct for the classifica- Medicine, University of Ferrara, and refined histological classification. The direct tion of gynaecological malignancies that improves Ferrara, Italy 1 3 consequence has been the progressive introduction of interobserver reproducibility and has the poten- Laboratory of Technology for new immunostainings for diagnostic and classification tial of revealing unexpected features. However, Advanced Therapies (LTTA), University of Ferrara, Ferrara, purposes. Hence, we review the routine diagnostic use interpretation in the light of knowledge-based Italy of immunohistochemistry in the field of gynaecological specificity of each single marker along with histo- 4Departments of Pathology, neoplasia. We reviewed the immunomarkers useful pathology expertise and stringency is still the sine Hamamatsu and Hiroshima in gynaecological pathology according to literature qua non. A satisfactory IHC must localise cells and Universities Schools of Medicine, Seirei Mikatahara Hospital, revision, our personal experience and research findings. tissue targets, clearly and specifically, keeping the Hamamatsu, Japan We discuss the application of immunohistochemistry to non-specific background to a minimum level. 5Department of Pathology, reach the most accurate diagnosis in morphologically Here, we will describe the panels of IHC markers Johns Hopkins University equivocal cases of gynaecological pathology and used in the most common scenarios of differential School of Medicine, Baltimore, present the appropriate panel of immunomarkers in the diagnosis seen in routine gynaecological pathology, Maryland, USA most common scenarios of gynaecological pathology. along with their rationale. Though beyond the Correspondence to This short review provides an updated overview of the scope of this paper, clinical information and macro- Dr Elisabetta Kuhn, Department essential immunohistochemical markers currently used scopical and microscopical features will be outlined of Morphology, Surgery and in the diagnostics of gynaecological malignancies along at times since they still represent a keystone for Experimental Medicine and with their molecular rationale. the correct diagnosis and characterisation of many Laboratory of Technology for pathological entities. Advanced Therapies Centre, University of Ferrara, Ferrara 44121, Italy; elisabettakuhn@ hotmail. it and Professor INTRODUCTION LOOKING at THE OVARY Ayse Ayhan, Department Immunohistochemistry (IHC) combines micro- Primary ovarian tumours are summarised in three of Pathology, Hamamatsu scopic morphology with accurate molecular iden- main subgroups with well-defined clinicopatho- http://jcp.bmj.com/ University School of Medicine, tification and allows in situ visualisation of any logical characteristics: epithelial, germ-cell and Handayama 1-20-1, 431- 2 3192 Hamamatsu, Japan; specific protein antigen. The introduction of IHC sex-cord stromal tumours (table 1). However, ayseayhanjp@ gmail. com in diagnostic pathology has revolutionised routine metastatic tumours and primary tumours derived practice, and IHC studies have significantly contrib- from non-ovarian-specific lymphoid or stromal EK and AA contributed equally. uted to a better understanding and subtyping of cells (ie, lymphomas, leukaemias and soft-tissue Received 12 September 2017 many malignancies, initially lymphoid neoplasms. tumours) should not be ignored since they repre- on November 6, 2020 by guest. Protected copyright. Revised 2 November 2017 Furthermore, IHC has become an integral part of sent a large proportion of ovarian malignancies. Accepted 3 November 2017 the definition of the majority of solid tumours and Currently, PAX8 is emerging as the most specific Published Online First is progressively gaining a foothold in guiding anti- marker to distinguish a primary ovarian carcinoma 7 December 2017 cancer therapy. Among other examples, HER2/neu from a metastasis, but it lacks sensibility as it is and oestrogen receptor (ER) expression is routinely also expressed in metastasis from the endocervix, used to identify patients with breast cancer eligible kidney and thyroid (see figure 1 and table 2).1 The to trastuzumab and tamoxifen, respectively. most common malignancy of the ovary is high- With the boost and consequential widespread use grade serous carcinoma (HGSC) that together with of advanced technologies, molecular studies that other serous tumours of the adnexa (low-grade claim to have discovered novel candidate makers serous carcinoma and borderline serous tumour) with diagnostic, predictive, prognostic or thera- are now thought to derive from the fallopian tube peutic value are published daily. In this context, the epithelium.3 4 Coherently, these tumours demon- responsibility of the pathologist is increasing. Besides strate consistent nuclear expression of Müllerian making tissue diagnosis, they are also in charge of marker WT1, which is highly expressed in the (1) guaranteeing the adequacy of samples used for normal tubal epithelium.3 WT1 is the most sensitive diagnostic tests, which will be translated into ther- and specific marker for serous histotype and can be apeutic decisions, (2) performing IHC biomarker used to discriminate serous tumours from all other To cite: Kuhn E, analysis and (3) assisting the development of novel histotypes. Ayhan A. J Clin Pathol tissue biomarkers. Over the last decade, molecular Recently, a practical approach to the use of IHC 2018;71:98–109. studies have unveiled the molecular genetic pathway in the classification of primary ovarian carcinomas 98 Kuhn E, Ayhan A. J Clin Pathol 2018;71:98–109. doi:10.1136/jclinpath-2017-204787 Kuhn E, Ayhan A. Ayhan A. Kuhn E, J Clin Pathol Table 1 Clinicopathological characteristics of ovarian tumours Laterality 5-year Differential 2018; Frequency Mean age (mean size) Stage Macro Micro Grade Chemoresponse survival diagnosis 71 Primary ovarian malignancies :98–109. doi:10.1136/jclinpath-2017-204787 :98–109. HGSC 70% 63 Bilateral III–IV Papillary, solid-cystic with necrosis and Solid, papillary and glandular growth of large cells with pleomorphic nuclei High Good 30% EMC, CCC, TCC, LGSC haemorrhage and prominent nucleoli. Brisk mitotic activity LGSC 3%–5% 53 Bilateral III Cystic, papillary with calcifications Small nest or micropapillae of uniform cells with mild–moderate atypia within Low Moderate 85% HGSC, CCC, SBT stroma. Psammoma bodies. Associated with SBT EMC 10%–15% 58 Unilateral I Solid or Solid-cystic Back-to-back tubular or cribriform glands, focally mucinous, secretory or Low Good 78% MC, HGSC, metastasis (15 cm) squamoid endometriosis CCC 5%–10% 55 Unilateral I Solid-cystic Tubulocystic, papillary and solid growth, clear cuboidal cells, sometimes High Poor 75% HGSC, mixed HGSC/ (15 cm) eosinophilic, papillae hyalinised stroma, with endometriosis EMC, LGSC, YST MC 3% 45 Unilateral I Solid-cystic Variably atypical cells with expansile or destructive invasive pattern. Low Poor >90% Metastasis (>12 cm) Heterogeneous tumours with benign, MBT and carcinoma features SMC Rare 40–50 Bilateral I Solid or solid-cystic Mixture of Müllerian cell phenotypes associated with SMBT Low NA Poor HGSC, EMC MMMT 2% 60 Unilateral III Solid with necrosis and haemorrhage HGSC or EMC component plus sarcomatous component, either non-specific or High Moderate 15%–30% HGSC, EMC with (14 cm) heterologous (chondro, rhabdomyo, osteo, lipo) spindle elements GCT 1% 53 Unilateral I Solid-cystic Diffuse, trabecular, insular or microfollicular growth pattern of uniform small Low Moderate 60% HGSC, SCC-HT (10 cm) cells with round to oval nuclei, rare grooves and scant pale cytoplasm SCC-HT Rare 20 Unilateral III Solid-cystic, pale with necrosis and Diffuse pattern with follicle-like spaces, small homogeneous hyperchromatic High Moderate 40% HGSC, GCT (15 cm) haemorrhage cells, mitotically active, sometimes with intermingled larger eosinophilic cells with large nuclei and prominent nuclei Metastatic adenocarcinoma* Colorectal Common 70 Bilateral IV Solid, friable with necrosis and haemorrhage Small or large glands, often cribriform, composed of non-mucinous atypical High NA Poor MC (12 cm) cells with central dirty necrosis Biliopancreatic Rare 60 Bilateral IV Solid-cystic Small or large glands into desmoplastic stroma or scarce stroma Variable NA Poor MC, MBLT Mammary Common 49 Bilateral IV Solid Ductal or lobular carcinoma High NA Poor EMC (<5 cm) (with a 3:1 proportion) Appendiceal Rare 45 Bilateral IV Multicystic and mucoid or solid and firm Low-grade mucinous neoplasm with abundant mucin or mucinous Low/high NA Good or MC, MBLT (15/11 cm) adenocarcinoma, that is, goblet cell carcinoid, signet ring carcinoma or poor intestinal-type adenocarcinoma Gastric Common 43 Bilateral IV Solid, firm, oedematous Signet ring cells arranged in tubules or sheets