3^rd Annual Meeting, Birmingham 2006

Commentaries on case presentations

Dr Godfrey Wilson

Case 1 – labelled A GW1

Clinical history - 31 year old female. Radical hysterectomy for cervical tumour which measured 4.9 cm in greatest dimension.

Section from the cervix.

Diagnosis                   Large Cell Neuroendocrine Carcinoma

The tumour has a predominantly solid and trabecular architecture being composed of cells with moderate amounts of pale eosinophilic cytoplasm.  The tumour nuclei exhibit moderate pleomorphism.  Frequent mitoses (>10/10 HPF) are observed and there are areas of necrosis.  Lymphovascular invasion was identified in several blocks of the tumour.  The tumour had a greatest dimension of 4.9cm.  There was no associated CIN or CGIN.  Immunocytochemistry showed strong positivity of the tumour cells for chromogranin, synaptophysin TTF-1 and p16 and focally for CD56.  These results together with the morphological features of the tumour indicate it to be a large cell neuroendocrine carcinoma (LCNEC).  The tumour extended to the anterior paracervical stromal margin.  One of 20 pelvic lymph nodes contained metastatic tumour.  The patient died 18 months later from recurrent disease, despite adjuvant chemotherapy (carboplatin and etoposide) and radiotherapy

Large cell neuroendocrine carcinoma of the cervix was first described in detail by Gilks et al in 1997.  Gilks reported 12 cases and cited 24 other non-small cell neuroendocrine tumours, some of which were also probable examples of LCNEC.   LCNEC is considered as a part of a spectrum of neuroendocrine tumours of the cervix, which also include carcinoid, atypical carcinoid and small cell carcinoma.  Carcinoid tumours are extremely rare, have an orderly nested/trabecular architecture and regular nuclei with dispersed chromatin.  Mitoses are very scanty and there is no necrosis.  Atypical carcinoids have similar architectural features but mitoses are more frequent (<10/10 HPF) with up to moderate nuclear atypia and there is often focal necrosis.  LCNEC are distinguished from atypical carcinoid by a more irregular architecture, loss of cytoplasmic definition, moderate to severe nuclear atypia, frequent mitoses (>10/10 HPF) and necrosis which may be geographic.  Small cell carcinomas are similar to their pulmonary counterpart being cellular tumours with small oval to spindle cells and with frequent necrosis.  The rarity of carcinoids and atypical carcinoids is emphasised and the reproducibility of the pathological subdivisions is therefore uncertain.    Mannion et al documented recurrences in 2 of 4 cases of atypical carcinoid though both patients were alive at last follow up.  In consequence, and given the extreme rarity of carcinoid and atypical carcinoid tumours, neuroendocrine neoplasms of the cervix should probably be viewed as a single clinicopathological entity from the perspective of clinical management.

LCNEC occur over a wide age range (21 to 76 years with mean of 34 years in the largest series).  Clinical presentation is similar to that of other forms of cervical cancer.  Patients typically present with an abnormal PAP smear or vaginal bleeding and a cervical mass.  Some patients have extra-uterine spread at presentation.  Typical features are as follows:-

Insular, trabecular, glandular and solid growth patterns

Necrosis, often of geographic type, is common

Medium to large tumour cells usually with eosinophilic cytoplasm

Eosinophilic granules are common within cytoplasm of tumour cells

Moderate to severe nuclear pleomorphism often with prominent nucleoli

High mitotic rate (>10/10 HPF and usually >20/10 HPF)

CGIN common (25-50% of cases)

May be associated with adenocarcinoma (which is usually of endocervical type) or small cell carcinoma

Variants include tumours with squamous differentiation and areas resembling adenoid cystic and adenoid basal carcinoma

Prominent lymphovascular invasion

Strong and diffuse positivity for CD56 and usually also for chromogranin and synaptophysin

Majority of tumours have identifiable HPV sequences, predominantly HPV 16 and HPV 18 with HPV 18 the commonest in most studies

Differential Diagnosis

Small Cell Carcinoma in which the tumour cells are smaller than LCNEC with minimal cytoplasm and moulded hyperchromatic nuclei.  Both small cell carcinoma and LCNEC are usually strongly and diffusely positive for CD56.  Small cell carcinoma is less commonly positive for chromogranin and synaptophysin

Poorly differentiated squamous cell carcinoma favoured if there is evidence of squamous differentiation (keratinisation, intercellular bridges) and if the neuroendocrine markers are negative.  P63 (homologue of P53) is almost invariably positive in squamous cell carcinoma while neuroendocrine carcinomas are negative

Adenocarcinoma favoured if glandular differentiation typical of the variants of cervical adenocarcinoma identified and if there is no or minimal positivity of the tumour for neuroendocrine markers.  Focal positivity of chromogranin in cervical adenocarcinoma is not uncommon and does not appear to influence prognosis.

Atypical carcinoid may be morphologically similar but is differentiated by mitotic activity of less than 10 mitoses/10HPF.  Necrosis is more focal than that generally seen LCNEC.

Prognosis

LCNEC has a similar poor prognosis to that of small cell carcinoma of the cervix.  70% of patients with LCNEC and with more than one year of follow up died of tumour 6 to 24 months after hysterectomy in one study.  Data from the SEER program which compared endocrine tumours (239 cases) and squamous cell carcinoma of the cervix indicated that endocrine tumours were likely to present at a higher FIGO stage, more likely to have lymph node involvement at diagnosis (57% vs 18%) and to have shorter median survival (22 months vs 10 years).  At all stages disease survival was worse for women with endocrine tumours compared to squamous cell carcinoma.

For these reasons combinations of chemotherapy, radiotherapy and surgery are indicated for endocrine tumours of the  cervix and unfortunately the relative rarity of these tumours result in difficulties in defining the ideal form of treatment

References

Gilks CB, Young RH, Gersell D, Clement PB, Large cell neuroendocrine carcinoma of the uterine cervix.  A clinicopathologic study of 12 cases.  American Journal of Surgical Pathology, 1997; 21; 905-914

Albores-Saavedra J, Gersell D, Gilks CB et al, Terminology of endocrine tumours of the uterine cervix: Results of a workshop sponsored by the College of American Pathologists and the  National Cancer Institute.   Archives of Pathology and Laboratory Medicine 1997; 121; 34-39

Michael H, Balega J, Sutton G, Roth LM, Neuroendocrine tumours of the uterine cervix: incidence and comparative histologic analysis. Modern Pathology 2000: 13: 128A

Koch CA, Azumin N, Furlong MA et al, Carcinoid syndrome caused by an atypical carcinoid of the uterine cervix. Journal of Clinical Endocrinology and Metabolism 1999; 84; 4209-4213

Mannion C, Park WS, Man YG et al, Endocrine tumours of the cervix – Morphologic assessment, expression of human papillomavirus and evaluation for loss of heterozygosity on 1p, 3p, 11q and 17p Cancer 1998; 83: 1391-1400

Albores-Saavedra J, Larraza O et al, Carcinoid of the uterine cervix; additional observations on a new tumour entity Cancer 1976; 38; 2328-2342

Albores-Saavedra J, Latif S, Carrick KS, Alvarodo-Cabrero I, Fowler MR, CD56 reactivity in small cell carcinoma of the uterine cervix. Int J Gynecol Path 2005; 24; 113-7

Kaufmann O, Georgi T and Dietel M. Utility of 123C3 monoclonal antibody against CD56 (NCAM) for the diagnosis of small cell carcinomas on paraffin sections  Hum Pathol 1997; 28; 1373-8

Wang TY, Chen BF, Yang YC et al Histological and immunophenotypical classifications of cervical carcinomas by expression of the p53 homologue p63: a study of 25 cases  Hum Pathol 2001; 32; 479-486

Savargaonkar PR, Hale RJ, Mutton A, Manning V, Buckley CH, Neuroendocrine differentiation in cervical carcinoma, Journal of Clinical Pathology 1996, 49; 139-141

McCusker ME, Cote TR, Clegg LX and Tavassoli FJ  Endocrine tumors of the uterine cervix ; incidence, demographics and survival with comparison to squamous cell carcinoma Gynecol Oncol 2003; 88: 333-9

Case 2 – labelled GW2

Clinical history - 45 year old female. Radical hysterectomy for cervical tumour which measured 3.2 cm in greatest dimension.  The tumour was identified following investigation of prolonged mucoid-like vaginal discharge.

Section from the cervix.

Diagnosis       Intestinal Type Mucinous Adenocarcinoma

The cervix from the radical hysterectomy specimen contains an excessive population of well differentiated glands of varying size.  The distribution of the glands is partly lobular but predominantly diffuse indicating the presence of well differentiated adenocarcinoma.  The diffusely distributed glands have a partly irregular architecture with some loosening of the surrounding stroma and a minimal inflammatory cell response compatible with stromal invasion.  The tumour cells appear of intestinal type with a predominance of tall columnar cells with apical cytoplasm interspersed with plentiful goblet cells containing large, clear intracytoplasmic vacuoles.  Smaller numbers of endocrine cells with infra-nuclear eosinophilic granules and scanty Paneth cells with supranuclear granules are also present.  The latter are not prominent within the slide that has been circulated but were prominent within the tumour contained within the preceding cone biopsy.   There is only mild cytological atypia.  Mitoses are identified but are very infrequent.   The epithelium of the endocervical canal and endocervical crypts is extensively replaced by similar epithelium indicative of a co-existent in-situ component (intestinal type CGIN).   No areas of CIN are identified and there are no features within the loop biopsy or consequent radical hysterectomy specimen indicative of HPV infection.     Immunocytochemistry shows the tumour to be strongly positive for CK7 and p16 and focally positive for CA125 and CEA.   Oestrogen receptor, progesterone receptor and CK20 are negative.  The overall appearances are those of a primary intestinal type mucinous adenocarcinoma of the cervix with associated CGIN of intestinal type.

Enteric type differentiation is not uncommon within cervical adenocarcinomas particularly of endocervical type and also adenosquamous carcinoma.  Pure intestinal type mucinous adenocarcinomas of the cervix are, however, very uncommon and have only very rarely been reported in the literature.  The tumours are characterised by glandular epithelium in which there is an admixture of intestinal type cells including columnar, goblet, endocrine and Paneth cells.  Outside of the gastrointestinal tract such tumours have also been described in the gall bladder, urinary bladder and sinonasal region as well as in the cervix.  Those tumours reported within the cervix do not appear to have had an adverse prognosis when compared to other histological subtypes of cervical adenocarcinoma.   The occurrence of intestinal metaplasia and CGIN in associated with intestinal type adenocarcinoma is previously described.  It is presumed that such intestinal differentiation is an example of “neo-metaplasia” occurring within Müllerian epithelium as such tumours are assumed to be of Müllerian origin.

The in-situ component in this case strongly favours the tumour being of primary cervical origin.  The differential diagnosis could however include metastatic colorectal adenocarcinoma involving the cervix.  Immunohistochemistry will be helpful in resolving this differential given that the rare cases of cervical intestinal type adenocarcinoma studied by immunohistochemistry have been positive for CK7 and negative for CK20 and Cdx-2 with opposite results for metastatic colorectal adenocarcinoma.

References:

1)         Azzopardi JG, Hou LT.  Intestinal metaplasia with argentaffin cells in cervical adenocarcinoma.  J Pathol 90:686-690, 1985.

2)         Lee KR, Trainer TD.  Adenocarcinoma of the uterine cervix of intestinal type containing numerous Paneth cells.   Arch Pathol Lab Med 114:731-733, 1990.

3)         Savargaonkar PR, Hale RJ, Pope R, et al.  Enteric differentiation in cervical adenocarcinomas and its prognostic significance.  Histopathology 23:275-277, 1993.

4)         Jaworski RC, Pacey NF, Greenberg ML, Osborn RA.  The histologic diagnosis of adenocarcinoma in-situ and related lesions of the cervix uteri.   Cancer 1988; 61; 1171-1181.

5.         Raspollini, MR, Baroni G, Taddei A, Taddei GL.  Primary cervical

            adenocarcinoma with intestinal differentiation and colonic carcinoma metastatic to cervix.  An investigation using Cdx-2 and a limited immunohistochemical panel. Arch Pathol Lab Med 2003; 127: 1586-1590

Dr Sanjiv Manek

Case 1 – labelled SM1

Clinical history - 39 year old female. Removal of vulval cyst. On macroscopy - 25 mm diameter, firm consistency, white cut surface, no cyst.

Section from the mass

Details:  A 39-year-old female presented with a vulval ‘cystic’ mass.  This was removed in entirety and measured 25mm in diameter.  It was not cystic but rather firm in consistency and its cut surface was white.

Histology

This is a well-circumscribed lesion comprising of clusters of acini separated by interlobular ducts set within a slightly hyalinised paucicellular fibrous stroma.  The lining of the glands comprises of a luminal epithelial and an outer myoepithelial layer.  In the inner lining cells, focal apical snouts are seen.  Some acini contain secretions.  There is subtle condensation of the stroma around ducts and acini.  No atypia is recognised and there is no evidence of malignancy. 

The features are of a fibroadenoma in mammary-like glands of the vulva.  With such characteristic appearances, there is no differential diagnosis.

Discussion

Such lesions have been termed variously as perianal apocrine gland adenoma, adenoma of anogenital mammary-like glands, papillary apocrine fibroadenoma and most commonly, fibroadenoma.  The term fibroadenoma is preferred because it is similar to the lesion in the breast and it is characterised by a combination of glandular and stromal elements.  It is considered to arise from supernumerary mammary tissue representing the caudal remnants of the milk duct.  However, the existence of such remnants has been challenged and instead, the theory of novel cutaneous glands, termed the anogenital mammary-like glands, has been proposed.  These are similar to eccrine, apocrine and mammary glands.  The focal apical snouting of the present case could support this theory.  Mammary-like glands are located primarily in the interlabial sulcus of the vulva and in smaller numbers, in the perineal and perianal skin.  Their morphology varies from simple coiled tubular glands to complex branched glands with acini set in either fibromyxoid or collagenous stroma.  They communicate directly with the skin.  It has been suggested that the commoner lesion, hidradenoma papillofirum, is also derived from these glands.  It is also proposed that some adenocarcinomas in this region, including extramammary Paget’s disease (cf. Toker cells), have the same derivation.

Hormonal influences may play a role in the development of such lesions.  In the present case, there is no history of any hormonal therapy, however.

The lining epithelium has been shown to express at least the progesterone receptor and stains, positively with CK7.  The outer, myoepithelial layer stains positively on immunohistochemistry with smooth muscle actin and S100.

Other lesions of these glands have been described, including adenocarcinoma, sclerosing adenosis and ductal carcinoma in-situ.

References

1.      Fibroadenoma of the mammary-like glands of the vulva. 

JD Sington, S Manek & K Hollowood.

Histopathology 2002; 41(6): 563-5.

2.      Adenoma of anogenital mammary-like glands.

P Donati, A Amanlea.

Am J Dermatopathol 1996; 18: 73-6.

3.      Mammary-like glands of the vulva and their disorders.

SCJ Van der Putte.

Int J Gynaecol Pathol 1994; 13: 150-60.

Case  2– labelled SM2

Clinical history - 29 year old female. Removal of vulval cyst. On macroscopy – Circumscribed mass ,15 mm diameter

Section from the mass

Details:  A 29-yer-old female presented with a vulval mass.  This was removed (?incompletely) and measured 15mm in diameter.  It was circumscribed.

Histology

This is a reasonably circumscribed but unencapsulated lesion comprising a network of medium-sized arterioles and smaller vessels set in a collagenous spindle-cell stroma.  The collagen is in the form of short wispy bundles and the spindle cells are loosely aggregated in short fascicles.  The arterioles have moderately thick hyalinised walls.  Focal peripheral inflammation is noted.  At one edge, there is fibrotic adipose tissue within which there are pleomorphic nuclei.  Mast cells are present throughout the lesion, including within the pleomorphic tissue.  No mitotic activity is apparent. 

The features are of a cellular angiofibroma with focal symplastic atypia.

Discussion

The overall features are classical for a cellular angiofibroma.  The unusual pattern is the associated foci of atypia, similar to symplastic change sometimes seen in uterine leiomyomas.  When cellular angiofibromas were first described, it was not readily recognised that a wider morphological spectrum could be encountered until recently when a series of cellular angiofibromas in the vulva were described and discussed (McCluggage et al).

Adipose tissue has been described in cellular angiofibromas, both at the periphery and within the main lesion.  Lymphoid aggregates have also been noted and the presence of stromal mast cells documented.  The present case has all these features.  In the series of cellular angiofibromas by McCluggage et al., one case did have focal marked nuclear pleomorphism and this appeared to be associated with adipose tissue.  The present case is likely to be another similar lesion where the pleomorphic cells are at the periphery within adipose tissue.

Cellular angiofibromas are characteristically vimentin positive and smooth muscle markers negative and almost all express ER and PR.  CD34 can be positive.  Despite the focal pleomorphism, cellular angiofibromas appear to behave in a benign fashion and recurrence is likely due to incomplete excision in the first place.

The main differential diagnoses are:

·         Aggressive angiomyxoma (deep and poorly circumscribed and less cellular with myxoid stroma)

·         Angiomyofibroblastoma (alternating hypo- and hypercellular areas with epithelioid/plasmacytoid cells around blood vessels.  Desmin positive).

·         Fibroepithelial stromal polyps (polypoid with lesional cells right up to epidermis)

·         Superficial cervicovaginal myofibroblastoma (desmin positive, lace-like areas)

·         Smooth muscle neoplasms

·         Fibromatosis (poorly circumscribed)

·         Solitary fibrous tumour (alternating hypo- and hypercellular areas and haemangiopericytoma-like vascular pattern.  CD34 positive)

·         Spindle cell lipoma (CD34 positive, major component, no thick-walled blood vessels).

References

1.      Cellular angiofibroma and related fibromatous lesions of the vulva: report of a series of cases with a morphological spectrum other than previously described.

W G McCluggage, R Ganesan, L Hirschowitz & T P Rollason.

Histopathology 2004; 45: 360-8.

Dr Robin Moseley

Case 1 – labelled Q05 1795 RM1

Clinical history - 33 year old female. Ovarian tumour

Section from the ovary

Case 2 – labelled S01 49 RM2

Clinical history – Vaginal biopsy of red area.  Previous hysterectomy

Section from vaginal biopsy

Dr Neeta Singh

Case 1 – labelled 12183 NS1

Clinical history - 29 year old female. 13 cm left ovarian cyst.  Left oophorectomy

Section from the ovary

DIAGNOSIS

Mature cystic teratoma with highly specialised neural tissue.

Longitudinal sections through the ‘tadpole’ show a cystic space (ventricle) with choroid plexus. Running along the length of the ‘tadpole’ is a tubal space (neural tube) lined by ependyma. The body of the ‘tadpole’ is composed of mature neural tissue. There are more cellular areas containing neurones and glial cells and less cellular areas containing only glial cells. This is probable attempted differentiation towards grey and white matter.

The eye like strucure shows pigmented retinal type epithelium.

Sections from other parts of the ovary show typical features of a mature cystic teratoma lined by keratinising squamous epithelium, with skin adnexa and focal giant cell reaction.

To our knowledge there are no previously described cases of a similar lesion.

REFERENCES:

1. Spaun E, Rix P.1990. Benign cystic monodermal teratoma of  neurogenic type. International Journal of Gynecological Pathology.9:283-290.

Case 2 – labelled 02 00115 NS2

Clinical history - 51 year old female. 25 cm large complex ovarian mass. CA125 – 158.5.  5 month history of emotional changes, abdominal discomfort and voice change.

Section from the ovary

Diagnosis.

Transitional cell carcinoma of the ovary with a functioning stroma causing virilisation.

Light microscopy showed morphological appearances typical of a transitional cell carcinoma.  There were no elements of a Brenner tumour in the background. The stroma appeared hypercellular.

Immunohistochemistry showed positive staining of the epithelial cells with CAM 5.2. The tumour cells were negative for CA125. Due to the virilising features staining with inhibin and alpha GST was performed. This showed strong positive staining of the stromal cells.

The endometrium was inactive with no evidence of hyperplasia.

Endocrine manifestations occur in less than 5% of all ovarian tumours and virilising tumours in post menopausal women are even rarer. Causes of excess androgen production in females

1.      Adrenal hyperplasia

2.      Adrenal cortical carcinoma

3.      Ovarian tumours

Non functioning tumours of the ovary which show evidence of hyperandrogenism are well described. In several of these cases, hyperplasia of the adjacent stroma with or without luteinisation has been noted, and this is thought to be the source of steroid secretion. Alpha glutathione S-transferase, a dimeric isoenzyme, shown to be present within steroid producing cells of the ovary, often shows cytoplasmic staining in adjacent stroma of these tumours.

Theories of why stromal cells react in this way include the mechanical effect theory which likens the stromal cell reaction to that around an expanding follicle.

The trophic effect theory postulates that the tumour cells produce a substance that stimulates the adjacent stroma.

It is important for clinicians and pathologists to be aware of the possibility of androgen production by non functioning epithelial tumours to help in correct management of patients.

References:

1. Scully RE. Ovarian tumours with functioning stroma. In: Fox H, Wells M,eds.

     Obstetrical and gynecological pathology,4^th ed. Edinburgh: Churchill Livingstone,     1995:983-96.

2. Tiltman AJ, Ali H. Distribution of alpha glutathione S-transferase in ovarian neoplasms: an immunohistochemical study. Histopathology2001;39:266-72.

Dr David Millan

Case 1 - labelled - 13713 DM1

A 20 year old woman presented with a supraclavicular lump. Initial investigations were suggestive of a lymphoma. Imaging, however, revealed lymphadenopathy and a solid /cystic pelvic mass. Her biochemistry was also found to be abnormal with raised calcium.

At operation an intact multinodular ovoid mass was present in the pelvis .This measured up to 200 mm. in length  .On opening there were cystic areas containing degenerate blood and solid areas of soft fleshy tissue .There were also multiple tiny white papules over the surface of the omentum.

The section is from the ovarian tumour.

The section from the edge of the ovarian tumour consists of sheets of medium size cells with large central nuclei with prominent nucleoli and a small amount of surrounding eosinophilic cytoplasm. Mitotic figures are frequent and apoptotic bodies are prominent. There is no notable tumour architecture other than the diffuse sheets of cells. Lymphovascular space invasion is easily seen. In some sections there are also small pre-existing tubal elements at the edge of the section.

The section was chosen to include a smaller component represented by a different population of small closely packed cells with indistinct cytoplasm and smaller, often smudged, nuclei with indistinct nucleoli. Mitotic figures are again easily seen. There are also areas where the two cell populations are mixed.

Immunohistochemistry revealed positive staining with epithelial markers, Vimentin and EMA. Inhibin, S100, Melan A, CD99 and lymphoid markers were negative. Neuroendocrine markers showed only weak positivity with PGP9.5.

The tumour is a small cell carcinoma of hypercalcaemic type which can have areas where the cells are less typically small cell in type.

 In this specimen from the ovary, the more typical small cell component made up a major part of the tumour. In contrast, the metastatic tumour deposits contained much more of the large cell population.

This is a rare tumour usually seen in younger women which is usually, but not always, associated with hypercalcaemia .It was first described in 1982 and is distinct from the small cell carcinoma of pulmonary type. The differential diagnosis is that of other small cell tumours including granulosa cell tumours, melanoma, lymphoma, primitive neuroectodermal tumours and other small round blue cell tumours.

There have been a number of clinicopathological reports which have shown that this is an aggressive tumour which is relatively resistant to chemotherapy. The stage of the tumour is a major prognostic factor, most long term survivors have had tumours confined to the ovary. The majority of patients die within two years from the time of diagnosis.

The relative rarity of this tumour has hindered any substantial investigation of the optimal means of its treatment but the sharing of experience in the Gynaecological Cancer Intergoup has raised the possibility of a trial using chemo and radiotherapy.

References

Dickersin GR et al. Small cell carcinoma of the ovary with hypercalcemia: a report of 11 cases Cancer 1982; 49:188-97

Young RH et al. Small cell carcinoma of the ovary, hypercalcemic type. A clinicopathological analysis of 150 cases. Am J Surg Path 1994; 18:1102-16

McCluggage et al. An immunohistochemical analysis of ovarian small cell carcinoma of hypercalcaemic type. Int J Gynecol Pathol 2004; 23:330-6

Case 2 labelled - 11406  DM2                       

A 17 year old patient with streak gonads who is phenotypically female.

At operation a streak gonad was seen on one side .A more normal looking ovary was seen on the other side .There was a rudimentary uterus and cervix and a perfectly formed vagina and cervix.

The section is from the more normal looking ovary.

The section from the more normal looking ovary is a tumour with discrete islands of cells lying within a fibrous stroma and with frequent areas of calcification. The islands have prominent rounded areas of hyalinised basement membrane like material and contain a mixture of larger germ cells and smaller sex cord like cells. The hilum of the ovary also contains leydig cells and tubular structures.

A feature which is more prominent in some islands is the relative predominance of the larger germ cells. In other areas there is crush artefact which blurs the boundary between the cellular islands and the surrounding stroma .Although worrying; there is no more obvious in situ or infiltrating tumour.

The patient presented with primary amenorrhoea, is not virilised, is known to have pure gonadal dysgenesis, has a XY karyotype and has been followed up by the paediatricians. The patient has a normal uterus and fallopian tubes. These were not removed.

The tumour is a gonadoblastoma.

A gonadoblastoma is considered to be a mixed germ cell sex cord stromal tumour which arises most commonly in dysgenetic gonads. The tumour is commonly associated with a germ cell tumour, usually a dysgerminoma. This was the reason why this patient had laparoscopic removal of both ovaries.

 The contralateral ovary is a typical streak gonad with no evidence of tumour.

 Female genitalia appear to develop by default .In this case there has been a mutation(s) which have halted the development of normal testicular tissue.

The term gonadoblastoma was introduced in 1953 by Dr RE Scully and it is his review of 74 cases published in 1970 which is one of the most authorative accounts of this rare tumour.

More recent publications address the complex molecular pathology associated with mechanisms of dysgenetic gonadal development.

References

Scully RE: Gonadoblastoma: A gonadal tumour related to the dysgerminoma (seminoma) and capable of sex hormone production.

Cancer 6: 445-463, 1953

Scully RE Gonadoblastoma: A review of 74 cases. Cancer 25:1340-1356, 1970