NATIONAL DIAGNOSTIC HISTOPATHOLOGY EQA
(Circulation 001 for the November 2011 TSL workshops in diagnostic histopathology)
FINAL RESPONSE ANALYSIS
Performance Assessment.
For an individual case to be used for scoring participants, at least 70% of respondents must have got the right or an acceptable diagnosis. Any case that does not meet this criterion will be considered an educational only case. And for the whole EQA to be used for individual performance assessment at least 10 scoring cases are required. This criterion has not been met in this circulation 001 and therefore this particular circulation will be considered entirely educational and not suitable for performance assessment. Hence there will be no scores for participants.
Details of each case including the original diagnosis are set out below for those who may wish to take another look at the slides.
1) Male born 01/04/1949. Multiple sclerotic metastases - ?lung/prostate/lymphoma. Suspicious lung lesion. 7mm core of bony tissue received.
CONSULTANTS: 90% of respondents agreed with the clinical information provided that this is a metastatic carcinoma. 50% decided that the most likely primary site is prostate while 10% each went for lung and lung/prostate. 20% did not specify a primary site.
10% of respondents decided that this is not a metastatic carcinoma but most likely an Osteoma possibly occuring in the context of Gardner's syndrome.
RESIDENTS: 76% of respondents agreed with the clinical information provided that this is a metastatic carcinoma. 46% of respondents decided the most likely primary site would be prostate while 30% of respondents did not specify any primary site. Unlike the consultants, 30% of respondents indicated that immunohistochemistry would be necessary to confirm the primary site.
15% of respondents decided that this is not a metastatic carcinoma but most likely a primary bone tumour such as osteosarcoma/osteoblastoma.
7.5% of respondents did not provide an answer for this case.
DIAGNOSIS: Metastatic carcinoma of pancreatic origin (CK7 and CA19.9 positive and CK20 negative). Following the histology report, a large pancreatic mass was found with imaging. On serology very high CA19.9.
DISCUSSION POINTS: The fact that this biopsy was from a metastatic tumour was already known before the biopsy was sent, therefore the only information added from morphological examination was to indicate that it is a metastatic adenocarcinoma. Clinicians sometimes require help to identify the primary site of a metastatic tumour which is important for treatment and prognosis (in less than 5% of metastatic cancer cases a primary site is never identified after exhaustive pathologic and radiologic investigations). This case emphasises the risk of rendering a misleading diagnosis by reliance on morphology alone or morphology with a guess based on knowledge of typical patterns of metastasis described in the literature. A pathologist without immediate access to immunohistochemistry should be able to indicate in his/her report after confirming a metastatic carcinoma that subject to finance, blocks could be sent elsewhere for further assessment that could lead to more specific information. This at least makes clinicians/patients aware that there is an option.
2)Female born 24th of July 1973. Laparoscopy NAD apart from 3-4 cm fluid filled cyst/vesicles in pouch of Douglas. 1 g of white tissue received.
CONSULTANTS: 30% of respondents considered this lesion to represent an ectopic gestation or mole and another 30% considered it to represent a cystic lesion from a mullerian/paramesonephric remnant. 10% respectively suggested a cystic lymphangioma, a peritoneal cyst and a neurofibroma. There was no answer to this case from 10%.
RESIDENTS: The majority (46%) of respondents considered this lesion to represent an ectopic gestation or mole. 15% thought it was an epithelial cyst. 7.5% respectively suggested an implant from an immature teratoma, a schwannoma, Serous papillary cystadenoma, a benign multicystic mesothelioma and a multilocular peritoneal inclusion cyst or cystic lymphangioma.
DIAGNOSIS:Benign multicystic mesothelioma
DISCUSSION POINTS: As indicated by many respondents and workshop participants, the tissue does bear some strong resemblance to foetal membranes. However what is clearly missing is definite chorionic villi and blood: indeed it is extremely difficult to identify even isolated red blood cells which is inconceivable in a specimen from products of conception! Similarly the absence of lymph (serous material with occasional lymphocytes) militates against the diagnosis of a lymphangioma. Although not really required for diagnosis, immunohistochemistry shown at the workshop clearly demonstrates positive staining of the lining mesothelial cells with calretinin.
3) Female born 2nd February 1951. Non-insulin-dependent diabetes mellitus, obesity, postmenopausal bleeding ? malignancy. 1.6 g of hemorrhagic tissue received from endometrial curettings.
CONSULTANTS: 30% of respondents diagnosed a complex endometrial hyperplasia (one mentioned with atypia). 20% diagnosed malignant mixed mullerian tumour. 20% diagnosed endometrial carcinoma. 10% diagnosed low-grade papillary adenocarcinoma of endometrium and 10% diagnosed endometrioid adenocarcinoma. 10% diagnosed a papillary metaplasia of endometrium.
RESIDENTS: 38% of respondents diagnosed endometrial adenocarcinoma with 7.5% each diagnosing endometrioid adenocarcinoma and papillary adenocarcinoma of endometrium. 15% diagnosed endometrial hyperplasia and 15% diagnosed endometrial polyps. 7.5% diagnosed a carcinosarcoma, and 7.5% diagnosed a chronic endometritis.
DIAGNOSIS: low-grade endometrial adenocarcinoma.
DISCUSSION POINTS: a diagnosis of endometrial adenocarcinoma needs to be made on endometrial curettings which means that reliance cannot be placed on identification of myometrium invasion. The major features in this sample that indicates the presence of endometrial carcinoma is complex glandular architecture as typified by groups of epithelial cells with secondary lumen formation (cribriform glandular structures). Rather than being merely closely packed, the glands share walls. In tiny foci necrosis is also noted.
It is noteworthy that in a significant proportion of cases where a complex endometrial hyperplasia has been diagnosed myometrium invasion is identified after hysterectomy.
4) Male born 21st of June 1943. Haematuria, abnormal cytology. Urethral growth avulsed. ? TCC/SCC/benign polyp. Specimen received (urethral biopsy) four white tissue fragments.
CONSULTANTS: 60% of respondents diagnosed a high grade (papillary) urothelial/transitional cell carcinoma. 10% each diagnosed pleomorphic rhabdomyosarcoma, schistosomiasis, poorly differentiated squamous cell carcinoma and Hodgkin's disease.
RESIDENTS: 84% of respondents diagnosed a (high grade) transitional cell carcinoma while 7.5% each diagnosed Hodgkin's lymphoma and rhabdomyosarcoma.
DIAGNOSIS:malignant melanoma (investigation in progress to exclude metastatic disease) - tumour cells were negative with broad-spectrum cytokeratins and Desmin but expressed S100 and HMB-45.
DISCUSSION POINTS:this is a case that strongly illustrates the limitations of practising pathology without access to immunohistochemistry. Certain diagnostic considerations do not even come to mind in such situations.
Overall it is important to remember that malignant melanoma is one of the great mimics in histopathology and should always be considered when a tumour appears very poorly differentiated. Also it is important to frequently entertain doubts about the impressions gained from initial morphological assessment and seek to confirm these with immunohistochemistry. There will always be the occasional surprise.
5) Female born 11th of December 1929. Right breast mass biopsy.
CONSULTANTS: 70% of respondents diagnosed an infiltrating lobular carcinoma while 10% diagnosed papillary carcinoma, invasive ductal carcinoma and DCIS with microinvasion respectively. One respondents used the code B5.
RESIDENTS: 46% of respondents diagnosed an invasive lobular carcinoma while 38% diagnosed an invasive ductal carcinoma. 7.5% each diagnosed malignant breast lesion and adenocarcinoma respectively.
DIAGNOSIS: Well differentiated invasive ductal carcinoma ? Infiltrating lobular element.
DISCUSSION POINTS: there are areas that show resemblance to infiltrating lobular carcinoma but definite well formed ducts are present. Although it was not done in this particular case but where it is necessary to differentiate between lobular and ductal carcinoma E-cadherin may be helpful (positive in invasive ductal and negative in infiltrating lobular carcinoma cells)
6) Female born 19th of June 1947. Left breast mass biopsy.
CONSULTANTS: 50% of respondents diagnosed an invasive ductal carcinoma (including variants such as tubular/cribriform). 20% diagnosed ductal hyperplasia. 10% respectively diagnosed suspicious for malignancy (B4), intraductal papilloma and fibroadenosis with moderate epitheliosis.
RESIDENTS: 46% of respondents diagnosed an invasive ductal carcinoma, while 15% diagnosed an atypical lobular hyperplasia. 7.5% each diagnosed fibrocystic disease, fibroadenoma, microglandular adenosis, sclerosing adenosis and DCIS.
DIAGNOSIS:well differentiated invasive ductal/tubular carcinoma
DISCUSSION POINTS: the angulated rather than rounded outlines of the tubules and the desmoplastic stromal response distinguish this tumour from benign mimics such as microglandular adenosis. Furthermore as shown during the workshop the absence of a basal layer can be demonstrated with markers such as p63, SMA, S100 and HMWCK.
7) Male born 15th of December 1942. PSA 7.9. Specimen received – prostatic needle core biopsy.
CONSULTANTS: 50% of respondents concluded that this is benign prostatic tissue while 40% diagnosed prostatic adenocarcinoma. 10% diagnosed a high grade prostatic intraepithelial neoplasia (PIN).
RESIDENTS: 61% of respondents concluded that this is benign prostatic tissue while 23% diagnosed prostatic adenocarcinoma and 15% diagnosed a prostatic intraepithelial neoplasia (PIN).
DIAGNOSIS: no evidence of malignancy.
DISCUSSION POINTS: the difficulty in this biopsy was presented by a small focus in which the acini were dilated with atrophy of their basal layer. The basal layer was highlighted by immunohistochemistry with high molecular weight cytokeratins (HMWCK) as shown during the workshop. Prostatic intraepithelial neoplasia has a lot in common as far as appearance is concerned with DCIS in the breast. There is no such lesion in this sample
8) Male born 10th of September 1949. PSA 32. Specimen received – prostatic needle core biopsy.
CONSULTANTS: All respondents diagnosed prostatic adenocarcinoma
RESIDENTS: All but 7.5% of respondents diagnosed a prostatic adenocarcinoma.
DIAGNOSIS: adenocarcinoma prostate.
DISCUSSION POINTS: this was apparently a straightforward and easy diagnosis of prostatic adenocarcinoma but such a diagnosis is not complete without accurate Gleeson grading (3+4 = 7 in this case). Immunohistochemistry was done purely for educational purposes and as shown at the workshop clearly demonstrated the absence of a basal layer around the malignant glands.
9) Male born 28th of July 1973. Right epididymal tumour present for many years. At surgery, not convincingly/definitely arising from epididymis. Specimen received - 6.2 g spherical mass measuring 25 x 22 x 20 mm with a white whorled cut surface.
CONSULTANTS: All but 10% (who diagnosed chronic inflammation in a cryptorchid testis) of respondents diagnosed an adenomatoid tumour.
RESIDENTS: All but 7 .5% of respondents (who supplied no answer to this case) diagnosed an adenomatoid tumour.
DIAGNOSIS: adenomatoid tumour.
DISCUSSION POINTS: adenomatoid tumour of the testis is not a common lesion. Very few pathologists indeed will come across the lesion in their routine practice. So it is quite interesting that nearly all pathologists including residents seem to be familiar with this lesion. Clearly its frequent appearance in postgraduate examinations has a role to play with this phenomenon.
How frequently pathologists come across various entities whether in routine practice, through courses or by means of EQA’s has a role to play in enhancing and maintaining diagnostic competence. Pathologists who see very few cases in any given year are not likely to be competent. It is very difficult to put exact numbers to it, but it is probably reasonable to say that an average pathologist needs to sign out a minimum of 1000 cases a year just to maintain basic diagnostic competence.
10) Female born 5th of November 1968. Menorrhagia LMP 12th of February 2011. Polyp noted at hysteroscopy. Specimen received - 2 g of white and brown tissue all processed.
CONSULTANTS: 30% of respondents diagnosed endometrial polyp with adenomyosis or leiomyoma and 30% diagnosed an endometrial carcinoma. 20% diagnosed an atypical polyploid adenomyoma (? malignant) and 10% each diagnosed a simple atypical endometrial hyperplasia and a malignant mixed mullerian tumour.
RESIDENTS: 38% of respondents diagnosed a carcinosarcoma/malignant mixed mullerian tumour. 23% each diagnosed an endometrial adenocarcinoma and an endometrial polyp. 15% diagnosed an endometrial hyperplasia.
DIAGNOSIS: atypical polyploid adenomyoma. Uterus from hysterectomy was normal.
DISCUSSION POINTS: fundamentally the lesion is seen in fragments of tissue comprising some atypical endometrial glands in a stroma of benign smooth muscle that resembles myometrium. While it may be easy to mistake it for endometrial carcinoma invading myometrium, the clinical information clearly indicates that it is an endometrial polyp and that the specimen received is endometrial curetting. Also there are many fragments of unremarkable proliferative phase endometrium in the background – there are no free fragments of endometrial carcinoma to be seen in the background, so where would endometrial carcinoma invading myometrium be coming from?
11)Male born 3rd Jan 1986. Lymph node biopsy from left groin ? Lymphoma.
CONSULTANTS: 40% of respondents diagnosed a reactive lymphadenopathy most likely from lymphogranuloma venarum. 30% diagnosed a non-Hodgkin's lymphoma and 10% respectively diagnosed Hodgkin's lymphoma, T-cell hyperplasia and kikuchi.
RESIDENTS: 53% of respondents diagnosed a non-Hodgkin's lymphoma while 30% diagnosed Hodgkin's lymphoma. 7.5% each diagnosed syphilis and Langerhans cell histiocytosis.
DIAGNOSIS: infectious mononucleosis. Follow-up information - history of weight loss over two months and a positive mono test.
DISCUSSION POINTS: immunohistochemistry in this case demonstrated that the interfollicular region in this lymphnode is expanded by a polymorphous infiltrate of T-lymphocytes including numerous blasts. This suggests a reactive process due to a virus or drug reaction. The typical background of Hodgkin’s lymphoma is not apparent and Reed-Stenberg cells are not apparent.
12) Female 29 years. Solitary femoral lymphadenitis.
CONSULTANTS: 40% of respondents diagnosed a Hodgkin's lymphoma while 30% diagnosed a non-specific reactive lymphadenopathy (including sinus histiocytosis and dermatopathic lymphadenitis). 10% each diagnosed cattleman's disease, non-Hodgkin's lymphoma and angioimmunoblastic lymphadenopathy.
RESIDENTS: 30% of respondents diagnosed a reactive lymphadenopathy while 23% diagnosed a non-Hodgkin's lymphoma. 15% diagnosed plasmacytoma while another 15% provided no answer. 7.5% each diagnosed Hodgkin's lymphoma and an immunodeficiency state.
DIAGNOSIS: ALK-1 positive anaplastic large cell lymphoma lymphohistiocitic variant.
DISCUSSION POINTS: this case was referred from Nigeria with a diagnosis of Hodgkin’s disease for confirmation with immunohistochemistry. There is definitely some resemblance to Hodgkin’s disease in terms of an appropriate background of a mixture of inflammatory cells in which a few scattered large cells are seen. But in this case the large cells are not Hodgkin’s cells – they are CD15 negative but CD30 and ALK-1 positive. This case illustrates the importance of good practice with respect to seeking to confirm every lymphoma diagnosis with immunohistochemistry.
13) Male 42 years, recurrent sinonasal tumour.
CONSULTANTS: 50% of respondents diagnosed plasmacytoma, 30% diagnosed an inflammatory polyp while 20% diagnosed non-Hodgkin's lymphoma.
RESIDENTS: 46% of respondents diagnosed plasmacytoma, 30% diagnosed inflammatory polyp, 15% diagnosed a nasopharyngeal carcinoma and 7.5% diagnosed an undifferentiated small cell tumour.
DIAGNOSIS: plasmacytoma.
DISCUSSION POINTS: Immunohistochemistry with kappa and lambda shown at the workshop clearly demonstrates a light chain restriction that confirms plasmacytoma. The plasma cells are quite well differentiated with only very occasional binucleate forms. However the sheer numbers/density of the infiltrate should raise the suspicion in the first place that will lead to a referral for confirmation.
14)Female 40 years, bilateral axillary lymphadenopathy.
CONSULTANTS: 30% of respondents diagnosed dermatopathic lymphadenopathy while 20% diagnosed a non-specific reactive change. 20% diagnosed Hodgkin's lymphoma. 10% each diagnosed a metastatic carcinoma, a metastatic malignant melanoma and a non-Hodgkin's lymphoma.
RESIDENTS: 30% of respondents diagnosed metastatic carcinoma while 23% diagnosed dermatopathic lymphadenitis. Another 23% diagnosed either a non-specific reactive lymphadenopathy or Castleman’s disease.
DIAGNOSIS: reactive lymphadenitis – dermatopathic.
DISCUSSION POINTS: in dermatopathic lymphadenopathy melanophages are often found in the lymph node and there is a proliferation of interstitial dendritic cells in the expanded interfollicular zone of the lymph node. All the features are present in this case.
15)Female 53 years, supraclavicular lymph node. Noticed small painless swelling left side root of neck x 3 weeks. Mobile, not tender with diameter of 2 mm.
CONSULTANTS: 30% diagnosed rhabdomyosarcoma, metastatic carcinoma (NOS) and non-Hodgkin's lymphoma respectively. 10% diagnosed metastatic medullary carcinoma from the thyroid.
RESIDENTS: 46% of respondents diagnosed a non-Hodgkin's lymphoma, 15% diagnosed metastatic carcinoma or provided no answer respectively. 7.5% diagnosed metastatic carcinoma from the thyroid, Hodgkin's lymphoma or non-specific reactive lymphadenopathy respectively.
DIAGNOSIS: metastatic medullary carcinoma from the thyroid (positive staining with broad spectrum cytokeratins and calcitonin)
DISCUSSION POINTS: this case was a referral from Nigeria to confirm an initial diagnosis of lymphoma by immunohistochemistry and the benefit of this good practice is clear. Some respondents/participants claimed to have identified amyloid like material between the cells that made them think of metastatic medullary carcinoma. However a lot appear to have been misled by the artefactual discohesiveness of the tumour cells that produced some resemblance to alveolar type rhabdomyosarcoma. Again a case illustrating the pitfalls of over-reliance on morphology alone. The right approach in this case was probably to diagnose metastatic tumour/carcinoma with referall for immunohistochemical assistance with identification of primary site.
16) Female, born 1979. Pelvic pain, Rt adnexal mass.
CONSULTANTS: 40% of respondents diagnosed a salpingitis and another 40% diagnosed a primary (serous papillary) adenocarcinoma of the fallopian tube. 10% respectively diagnosed a metastatic adenocarcinoma and an epithelial hyperplasia of the fallopian tube.
RESIDENTS: 60% of respondents diagnosed a primary adenocarcinoma in the fallopian tube while 30% diagnosed metastatic adenocarcinoma. 7.5% diagnosed a salpingitis.
DIAGNOSIS: chronic salpingitis.
DISCUSSION POINTS: There is clearly a chronic suppurative inflammation in the lumen and the connective tissue cores of the mucosal folds, complete with some cholesterol clefts/granuloma. A significant proportion of the inflammatory cells are foamy histiocytes with cleared cytoplasm.
There is atypia of the mucosal epithelium that is related to the inflammation. Furthermore fibrosis that is part of the chronic inflammatory process has resulted in the entrapment of some crypts at the periphery which misled the unwary to diagnose an adenocarcinoma. Primary adenocarcinoma of the fallopian tube does occur but is very rare indeed.