scotland and northern ireland eqa scheme circulation xx...• figo stage iib mixed adenocarcinoma...
TRANSCRIPT
![Page 1: Scotland and Northern Ireland EQA Scheme Circulation XX...• FIGO Stage IIB mixed adenocarcinoma and large cell neuroendocrine carcinoma with CIN 3 in ectocervix with LVSI and involvement](https://reader033.vdocuments.mx/reader033/viewer/2022060923/60aec1d4ac7fdc034a758ad1/html5/thumbnails/1.jpg)
Scotland and Northern Ireland
EQA Scheme
Circulation 46
Special Educational Cases E1 and E2
Presented by Dr K Robertson
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Case E1
• Female – 42 year old with heavy menstrual and intermenstrual
bleeding. IUS in situ for 3 years. Bloods normal (including CA125)
– Posterior uterine leiomyoma on ultrasound scan
– Treated with Norethisterone and tranexamic acid then switched to Ulipristal
– Persistent debilitating menorrhagia and abdominal discomfort. Underwent subtotal hysterectomy
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Case E1
• Macroscopy
– Distorted uterus measuring 120mm (SI) x 90mm
(left-right) x 85mm (anterior-posterior)
– Clotted blood in endometrial cavity
– Large lobulated pale fleshy lesion projecting into
endometrial cavity, involving the posterior wall of
the uterus. Invades outer half of myometrium.
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Case E1
• Additional information -
– Tumour is strongly positive for CD10
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CD10
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SMA x100
Desmin x 100
S100 x 100
• Additional information -
– Tumour is negative for SMA,
Desmin
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Case E1
• Also negative for
– Calretinin
– Inhibin
– EMA
– MelanA
– PanCK
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Case E1
• Diagnosis:
– Low Grade Endometrial Stromal
Sarcoma
– FIGO 1b (> 5cm in size)
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Case E1
• Responses: 92 responses in total
• 50 – Endometrial Stromal Sarcoma/Endometrial
Stromal Tumour/Stromal Sarcoma/Uterine
Stromal Sarcoma
• 40 – Low Grade Endometrial Stromal Sarcoma
• 1 – Endometrial Stromal Sarcoma – would do
molecular testing to distinguish Low Grade from
High Grade
• 1 – Endometrial Stromal Nodule
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Case E1
• Differential diagnosis
• Endometrial stromal sarcoma low grade
• Endometrial stromal sarcoma high grade
• Endometrial stromal nodule
• Other mesenchymal lesions
• E.g. cellular leiomyoma
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Case E1
• Endometrial stromal nodule
• Benign
• Well circumscribed margin • Can have limited infiltration (adjacent nests of tumour cells
measuring <3mm in greatest dimension from the main tumour mass and < 3 in number are acceptable)
• Cells resemble proliferative-phase endometrial stroma
• Most tumours harbour a t(7;17p21;q15) which results in a fusion between JAZF1 and SUZ12
• Immunoprofile identical to that of endometrial stromal sarcoma
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Case E1
• Low Grade Endometrial Stromal Sarcoma
• Malignant; <1% of all uterine malignancies but second
most common uterine mesenchymal malignancy
• Cells resemble proliferative-phase endometrial stroma
• Minimal cytological atypia
• Usually low mitotic activity although high mitotic rate does
not preclude diagnosis
• Infiltrative growth pattern and/or lymphovascular invasion
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Case E1
• Can show smooth muscle differentiation,
fibromyxoid change, sex cord-like
differentiation, and/or endometrioid-type
glands
• 10% involve the adnexae
• 30% have lymph node involvement
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Case E1
• Immunoprofile:
– Diffuse and strong positivity for CD10 (not always!)
– SMA and Desmin may be positive
– Negative for h-caldesom (positive in areas showing smooth muscle or sex cord-like differentiation)
– ER, PR and WT-1 typically positive
– Inhibin, calretinin, MelanA, CD99 in areas of sex cord-like differentiation
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Case E1
• Molecular
– Most tumours harbour a t(7;17p21;q15) which results in a fusion between JAZF1 and SUZ12.
– Other rearrangements also seen; t(6;7)(p21;p15), t(6;10;10)(p21;q22;p11) and t(1;6)(p34;p21)
• Prognosis
– Stage is most important predictive factor
– Five-year disease specific survival for Stage 1 and Stage II is 90% compared to 50% for stages III and IV
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Case E1
• High Grade Endometrial Stromal Sarcoma
– Malignant
– May coexist with low-grade ESS
– Round-cell morphology rather than spindle cell as in low-grade ESS
– Commonly shows confluent permeative and destructive growth with invasion into outer half of myometrium
– May have pseudo-papillary/glandular areas
– Mitotic activity typically > 10 per 10 hpfs
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Case E1
• Molecular
– Typically harbours the YWHAE-FAM22 genetic
fusion as a result of t(10;17) (q22;p13)
• Prognosis
– Earlier and more frequent recurrences compared to
low-grade ESS
– Better prognosis compared to undifferentiated
stromal sarcoma
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Case E1
• Learning points
• Not everything that looks like a leiomyoma
radiologically is a leiomyoma
• Good example of a rare tumour
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Case E2
• Female aged 33 years
– Irregular frequent bleeding
– Never had a cervical smear
– Fungating mass seen at cervix
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x40
Cervical Biopsies
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x400
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x600
Large pleomorphic and basophilic cells with stippled
chromatin admixed with eosinophilic cells, some of which
look ‘squamoid’ in appearance. No true glandular spaces and
ABPASD for mucin negative.
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ABPASD
Squamous markers CK5/6 and p63 NEGATIVE
x 200
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x 200
Synaptophysin
CD56
Chromogranin
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x 200
Ki67
p16
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MRI - 6cm ectocervical tumour
extending into vagina
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Case E2
• Biopsy Diagnosis:
– Large cell neuroendocrine carcinoma
– Combined poorly differentiated squamous cell carcinoma and large cell neuroendocrine carcinoma was considered but no definite evidence of squamous differentiation on the biopsy
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Case E2
• Treated with neoadjuvant chemotherapy (Carboplatin/Etoposide) and subsequently underwent a radical hysterectomy, bilateral salpingo-oophrectomy and pelvic node clearance
• FIGO Stage IIB mixed adenocarcinoma and large cell neuroendocrine carcinoma with CIN 3 in ectocervix with LVSI and involvement of the vagina
• Tumour showed little response to chemotherapy
• Post operative radiotherapy
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Case E2
• Responses: 92 in total
• 25– Cervical Small Cell Carcinoma
• 20 – Large Cell Neuroendocrine Carcinoma
• 19 – Neuroendocrine Carcinoma
• 18 - Poorly Differentiated Neuroendocrine Carcinoma
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Case E2
• Other responses :
• 3 – Poorly Differentiated Squamous Cell Carcinoma with
Neuroendocrine Differentiation
• 1 -Neuroendocrine Carcinoma (small and large cell)
• 1 -Small Cell Carcinoma with Squamous Component
• 1 -Neuroendocrine Carcinoma and Squamous Cell Carcinoma
• 1 -Undifferentiated Neuroendocrine Carcinoma
• 1 -Neuroendocrine Tumour
• 1 -Neuroendocrine Tumour/Neuroendocrine Carcinoma
• 1 -Neuroendocrine Carcinoma vs Poorly Differentiate SCC with NE Differentiation
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Case E2
• Large Cell Neuroendocrine Carcinoma
• Organoid, trabecular, cord-like or sheet-like growth
• Tumour cells larger than small cell carcinoma with
abundant eosinophilic cytoplasm
• Large nuclei, prominent nucleoli, and high mitotic
rate
• Geographic necrosis may be seen
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Case E2
• Differential diagnosis of Large Cell Neuroendocrine Carcinoma
• Small Cell Neuroendocrine Carcinoma
• Mixed Neuroendocrine Carcinoma and Squamous Cell Carcinoma/Adenocarcinoma
• Poorly Differentiated Squamous Cell Carcinoma
• Poorly Differentiated Adenocarcinoma
• Undifferentiated Carcinoma
• Atypical Carcinoid
• Malignant Melanoma
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Case E2
• Discussion
• Can coexist with a non-neuroendocrine carcinoma
• HPV 16 and 18 implicated as aetiological agents
• Aggressive behavior
• Small cell carcinoma of the cervix and LCNEC of cervix behave and are therefore treated similarly – MULTIMODAL treatment
• Poor five year survival (Stage 1 – 42%, Stage II – 19%, Stage III – 10% and Stage IV – 23% [McCusker et
al, Gyn Onc, 2003, 88(3):p.241-50]
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Case E2
• Learning points
• Nice example of a rare tumour
• Biopsies not always fully representative of the
entire tumour
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Scotland and Northern Ireland
EQA Scheme
Circulation 46
Special Educational Cases E3 and E4
Presented by Dr A Chapman
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Case E3
• Female 66 years
Polyp right posterior nasal septum
Presented with 10 month history of nasal
obstruction; mass extended from nasal cavity
towards nasopharynx; received was a tan-coloured
polypoid mass, 30 x 18 x 8mm.
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Case E3
• Diagnosis:
Respiratory Epithelial Adenomatoid Hamartoma
(REAH)
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Case E3
• 90 Responses:
• 34+3 – Respiratory Epithelial Adenomatoid Hamartoma
(REAH)
• 5+1 – seromucinous hamartoma
• 2 – seromucinous hamartoma vs REAH
• 2 – considered REAH but insufficiently thickened
basement membrane
• 6 – included “hamartoma”
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Case E3
• 90 Responses:
• 9 – benign nasal/septal polyp
• 8 – inflammatory (nasal septal/sinonasal) polyp
• 7 – sinonasal/nasal papilloma
• 6 – Schneiderian papilloma/polyp
• 6 – seromucinous polyp, fungiform nasal papilloma,
benign reactive, cylindrical cell papilloma, polypoid
hyperplasia in chronic rhinosinusitis, Papillary Sail –
Adenoma (a form of duct papilloma)
• 1 – Respiratory Epithelial Adenomatoid Carcinoma
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Case E3
• Differential diagnosis
• Seromucinous hamartoma - ?a spectrum
• Inflammatory sinonasal polyp, inverted papilloma,
low grade sinonasal adenocarcinoma
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Case E3 • Discussion
• Invaginated and tubular architecture with fewer discrete glands (but clearly arising in direct continuity with the surface epithelium)
• Periglandular stromal hyalinization is not prominent ?related to less glandular architecture
• “Stromal hyalinization may be prominent but is not seen in all cases” Wenig & Heffner, Fitzhugh & Mirani
• Mild inflammation but architecture too complex for inflammatory polyp
• Pre-existing seromucinous glands present; no haphazard proliferation of glands lined by single epithelial layer (seromucinous hamartoma)
• All lined by benign respiratory epithelium; no transitional/squamous epithelium with microcysts and neutrophils (inverted papilloma); no evidence of atypia or malignancy
• Immunohistochemistry…..
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Case E3
• Learning points
• Uncommon lesion
• First described in 1995 (Wenig BM & Heffner DK)
• Hamartomatous lesion – complete excision usually
curative: awareness is important to avoid
overdiagnosis and unnecessary surgical treatment
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Case E4
• Male 46 years
Total laryngectomy
Large polypoid mass in posterior larynx
Polypoid mass, 45 x 28 x 37mm, in the posterior
part of the larynx; vocal cords not abnormal;
encircled posterior parts of thyroid cartilages, close
to arytenoid cartilages and superior aspect of
cricoid cartilage
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DESMIN
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DESMIN
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MYO D1
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MYOGENIN
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Case E4
• NEGATIVE: smooth muscle actin, CD34, CD31
• Laryngectomy specimen had been decalcified.
• Immunohistochemistry performed on previous arytenoid biopsy containing the same tumour:
• POSITIVE: desmin, myoD1, myogenin, (weakly positive smooth muscle actin)
• NEGATIVE: MNF116, AE1/AE3, p63, S100, CD3, CD20 (mostly negative CD31 and CD34)
• No evidence of a FOXO1 gene rearrangement.
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Case E4
• Diagnosis:
Pleomorphic rhabdomyosarcoma
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Case E4
• 92 Responses:
• 12 - rhabdomyosarcoma
• 1 – pleomorphic rhabdomyosarcoma
• 12 – included/favoured rhabdomyosarcoma
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Case E4
• 92 Responses:
• 8 – sarcomatoid/spindle cell carcinoma
• 3 – leiomyosarcoma
• 1 – angiosarcoma
• 1 – melanoma
• 54 – high grade/poorly
differentiated/pleomorphic/anaplastic/spindle cell/giant
cell malignancy ?sarcoma ?sarcomatoid carcinoma
?melanoma ?lymphoma ?vasoformative ?synovial
sarcoma ?extraskeletal osteosarcoma ?MPNST
• 28 mentioned immunohistochemistry
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Case E4
• Differential diagnosis
• Spindle cell/sarcomatoid carcinoma – morphology,
squamous dysplasia/differentiation
• Other sarcomas (also very rare at this site),
melanoma, (lymphoma)
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Case E4
• Discussion
• Rhabdomyosarcoma of the larynx very rare
• Metastases to larynx also uncommon
• Not included in most recent WHO classification (discussion limited to specific entities often found in the larynx or that have an important differential diagnostic role)
• Difficult to stage accurately
• Poorly documented, all age groups affected, centred around glottic region, ?early presentation -> good prognosis?
• This patient is alive 20 months post laryngectomy but has pulmonary, mediastinal and left parapharyngeal metastases
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Case E4
• Learning points
• Very rare tumour but does occur in the larynx
• Diagnosis starts with morphology and assessment
of squamous dysplasia/differentiation but needs
appropriate immunohistochemistry
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