Dr Agata T Kochman Wishaw General Hospital

Dr Agata T Kochman
Wishaw General Hospital

Case E1
84 year old male
Symptoms: R shoulder pain
CT = thymic mass and (R) LL nodules + (L) lung nodule
Clinically metastatic lesions in lung with primary thymic tumour
? primary lesions – open (R) lung biopsy – lower lobe
Macro: A: Wedge biopsy of lung 27x20x11mm. A1 1/2. A2 – A6 1/1.
A/E and B: Shave biopsy of lung 15x10mm with a calcified part. B1 –
B3 1/1. A/E.

Case E1
The biopsy of lung shows small tumour nodules the largest measuring
3.1mms

Case E1
The tumour consists of sheets, nests and clusters of fairly uniform
cells with round, oval and spindle shaped nuclei with granular
chromatin and moderate pink granular cytoplasm
No mitoses or necrosis seen
The cells show peripheral nuclear palisading

Case E1 x20

Case E1 EMA

Case E1 MNF116

Case E1 CD56

Case E1 Synapto

Case E1 chromogranin

Case E1
MNF116/Pancytokeratin –negative
Epithelial membrane antigen – positive
TTF1 – patchy weak nuclear staining
CD56 – strongly positive
Synaptophysin – strongly positive
Chromogranin A ‐ positive

Case E1
HE summary:
Several nodular proliferations of neuroendocrine cells that have
cytologically bland nuclei and eosinophilic cytoplasm
These appear to be associated with scarring and each measure less
than 5mm in maximum dimension
The MIB1 proliferation index is extremely low (less than 5%)

Case E1
Small size of these tumours and the related scarring favours that these
represent primary tumourlets rather than metastatic carcinoid tumour
The only slight concern with this is the small nodule of tumour
(possibly in a lymphatic) at the pleural surface
TTF‐1 staining is not helpful since this can be positive in
neuroendocrine tumours from any site

Case E1
Tumorlets are nodular proliferations of neuroendocrine cells that are
normally present in the airways
Up to 4 mm in diameter in the airway wall (larger tumors are called
carcinoids)
Often multiple, and usually peripheral, they are characterized by
small nests of cells having neurosecretory granules
They lack mitoses and cellular atypia; typically, they have a hyalinized,
fibroelastic stroma

Lymph node metastases have been noted in 4 or 5 cases.
One case that was associated with Cushing's syndrome had tumor that
metastasized widely
In 36 cases, females predominated, 28 to 8, and the average age was 70

Case E1
It remains unclear whether material obtained from right lower lobe of
lung is representative of the thymic mass and left lung nodule.
Whilst a primary or metastatic carcinoid of the thymus is a possibility,
other lesions of the thymus cannot be excluded and it is impossible to
comment on the nature of the left lung nodule on the basis of this
material.

References
1. Churg A, Warnock M. Pulmonary tumorlet. A form of peripheral
carcinoid. Cancer 1976; 37:1469‐1477.
2. Pelosi G, Zancanaro C, Sbabo L, Bresaola E, Martignoni G, Bontempini
L. Development of innumerable neuroendocrine tumorlets in pulmonary
lobe scarred by intralobar sequestration. Immunohistochemical and
ultrastructural study of an unusual case. Arch Pathol Lab Med 1992;
116:1167‐1174.
3. D'Agati V, Perzin K. Carcinoid tumorlets of the lung with metastasis to
a peribronchial lymph node. Report of a case and review of the literature.
Cancer 1985; 55:2472‐2476.
4. Miller M, Mark G, Kanarek D. Multiple peripheral pulmonary
carcinoids and tumorlets of carcinoid type, with restrictive and
obstructive lung disease. Am J Med 1978; 65:373‐378.
5. Aguayo S, Miller Y, Waldron J Jr, Bogin R, Sunday M, Staton G Jr, Beam
W, et al. Idiopathic diffuse hyperplasia of pulmonary neuroendocrine cells
and airways disease. N Engl J Med 1992; 327:1285‐1288.

Case E2
84 year old female
Torted large left ovarian cyst, normal Ca125
TAH&BSO+omenctectomy done
Left ovarian cyst, 220x135x120mm, attached to fallopian tube, 125x5mm
and haemorrhagic broad ligament. The cyst is multilocular but the
capsule is intact. There are some serosal nodules under the intact
capsule, largest 50mm

Case E2
The serosal nodules consist mainly of a mixture of invasive moderately
differentiated mucinous cystadenocarcinoma mixed with invasive
malignant transitional cell tumour containing abnormal mitoses
Cystic tumour consists of well differentiated mucinous cystadenoma
The non‐ cystic component consists of benign transitional epithelium
mixed with benign mucinous cystadenoma

Case E2 x4

Case E2 x10
.

Case E2 x40
The mucinous cystadenocarcinoma shows small foci of ciliated serous differentiation.

Case E2 CEA

Case E2 Ca125

Case E2 CK20

Case E2 Ca19.9

Case E2
CK7‐Positive in all tumour components
CK20‐Negative
CEA‐Positive
CA125‐Positive in the non‐transitional mucinous component
CA19.9‐Positive
WT1‐Negative
CDX2‐ Negative
P53 Protein‐Negative
TTF1‐Negative

Case E2
Within the left ovarian cystic mass there is evidence of a benign
Brenner tumour with accompanying mucinous differentiation
In addition, there are small more solid areas of partly necrotic and
poorly preserved tissue where there is frank evidence of malignancy

Case E2
In addition, the malignant epithelial element shows a variety of
patterns of differentiation including areas of mucinous differentiation
and areas of serous differentiation
Technically this tumour would fall into the category of a malignant
mixed epithelial tumour
As the major component is actually made up of transitional cell
epithelium the tumour has been classified as a malignant Brenner
tumour with a minor component of mucinous and serous carcinoma

Case E2
A malignant Brenner tumor is a rare form of invasive epithelial
ovarian cancer
The histologic appearance of malignant Brenner tumor is similar to
that of transitional cell cancer of the ovary and transitional epithelium
of the urinary bladder
Immunohistochemical staining of malignant Brenner tumor often
demonstrates positivity for uroplakin III, thrombomodulin and
cytokeratin 7 and negativity to cytokeratin 20
The mainstay of treatment is surgical resection, but the exact regimen
and benefit of adjuvant therapy remain unknown

Case E2
Surface epithelial stromal tumours are the most common neoplasms
of the ovary and they encompass five distinct subtypes including
serous, mucinous, endometrioid, transitional and the clear cell types,
which mostly occur in the pure form
In some cases however, two or more subtypes reside within the same
tumour. These are known as mixed surface epithelial stromal tumours
The WHO has classified mixed tumours as those in which the minor
component is easily recognizable and they account for at least 10% of
the entire tumours on microscopic examination
Mixed epithelial tumours of the ovary comprises less than 4% of all
the ovarian epithelial stromal neoplasms; malignant, mixed epithelial
tumours are still rarer; most frequent: serous and endometrioid, the
serous and transitional cell carcinoma and the endometrioid and clear
all carcinoma types

Case E2
A. Uterus, endometrium – benign polyps – cystic glandular
hyperplasia.
Left ovary – combined mucinous cystadenocarcinoma, Grade 2 and
malignant Brenner’s tumour – ex‐combined mucinous cystadenoma
and benign Brenner’s tumour. PT1aNxMx. FIGO stage IA.
Right ovary – serosal adhesion – no tumour seen.
B. Omentum – normal
Brenner’s tumours are sometimes related to endometrial hyperplasia,
as in this case.
Post op: Bowel obstruction

References:
1. Lee KR, Tavassoli FA, Prat J, Dietel M, Gersell DJ, Karseladze AI, et
al. Tumours of the ovary and the peritoneum: surface epithelial stromal
tumours. In: Tavassoli FA, Devilee P eds .World Health Organisation
Classification of Tumours of the Breast and Female Genital Organs.
Lyon: IARC Press; 2003;144
2. Prat J. Ovarian endometrioid clear cell, Brenner’s and rare epithelial
stromal tumors. In Robboy JS, Mutter LG editor’s Robboy’s Pathology
of the Female Reproductive Tract. 2nd edition .Elsiever Churchill
Livingstone; 2009; 684
3. Eichhorn JH, Yong RH. Transitional cell carcinoma of the ovary:
a morphologic study of 100 cases with emphasis on differential
diagnosis. Am J Surg Pathol 2004 Apr; 28 (4): 453-63.
4. Balasa RW. Adcock LL, Prem KA, Dehner LP. The Brenner tumur, a
clinicopathologic review. Obstet Gynecol 1977; Jul, 50 (1): 120-8.

E3
Dr Hasan Vazir
Altnagelvin

Female, 32 years
E3
Diplopia and enlarged pupils for two months
Left medial rectus muscle biopsy

Diagnosis ‐ Amyloid
National Amyloid Centre, University College London Medical School,
confirmed amyloid and positive staining with Congo Red.
They carried out immunohistochemical studies antibodies to serum
amyloid A protein (SAA), kappa and lambda light chains. The amyloid did
not stain with any of these antibodies.
Interpretation: Amyloid of non AA type
The possibility of AL amyloid could neither be excluded nor confirmed by
present immunohistochemical analyses, as approximately 20% of AL does
not stain with antibodies against either kappa or lambda light chains.

In March 2010 the patient did not have macroglossia and no
organomegaly was detected on abdominal palpation. It was
concluded at that time that the patient did not have systemic
amyloidosis
She has localized orbital AL amyloidosis involving the medial
rectus muscle.
She is currently on follow up with no active intervention, which
was a decision arrived at with after discussion with the patient.

34E4
Dr Hasan Vazir
Altnagelvin

Female, 50 years
Large left ovarian cyst
E4
Normal CA125
• This lady presented with a large ovarian cyst
and dense adhesions with evidence of
endometriosis (clinical).

E4
‘Both ovaries contain endometriotic cysts. In
the left ovary are foci resembling Arias Stella
effect. In several sections, there is a small
neoplasm composed of glands widely
separated by abundant fibrous stroma. This
small lesion seems to emanate from the
endometriotic cyst’

E4
‘In areas, the glands are obviously endometrioid
but elsewhere have more nuclear atypia with
clear cytoplasm and even some signet ring
cells. I do not feel the morphological features
are typical of clear cell neoplasm ‐ I regard this
as an endometrioid neoplasm. Although
there are some worrying and unusual features,
I would be reluctant to make a diagnosis of an
adenocarcinoma.’

E4
‘This is best regarded as an unusual borderline
endometrioid adenofibroma arising from an
ovarian endometriotic cyst. Since the capsule
was ruptured, it is regarded as FIGO stage 1C.’

Circulation 34
Educational case 5
F82 Large lump L breast, clinically
malignant. Large volume core biopsy
as therapeutic procedure
H and E, ER, Ck5/6, S100 available
digitally

CK 5/6

S‐100

Diagnosis
Microglandular adenosis

Questionnaire
Forms returned 59
Attempted case ‐ 54
Offered a diagnosis 26
No diagnosis offered 28

Diagnoses
Microglandular adenosis 19
Adenomyoepithelioma 4
Tubular carcinoma 2
Myoepithelial lesion? Adenosis? 1

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