Qap (Anatomical Pathology AP99Q4)

[see history] [AP86][AP87][AP88][AP89][AP90][AP91]

AP86 Peer Review: Intendended Diagnosis: Lichen planus

Code

Dx Comment

Score

123

Lichen planus 100%

 

100

246

Lichen planus. 100% Immunofluorescence studies to confirm the diagnosis. 100

259

Lichen planus 100%

 

100

369

Lichen planus 100%

 

100

448

Lichen planus 100% Drug reaction sometimes causes lichenoid reaction, mimicking lichen planus. It has to be excluded. 100

517

Lichen planus 100%

 

100

663

Lichen P1anus 100%

 

100

815

Lichen planus 100% Discoid lupus canlook identical and also involve oral mucosa. Confirm diagnosis with direct immunofluorescence--interepithelial fibrin in lichen planus vs linear immunoglobulins in DLE. 100

873

Lichenoid mucositis consistent with Lichen Planus 100% Correlate with the gross and clinical findings 100

911

Lichen planus 100%

 

100

109

Lichen planus (100%)

 

100

301

Interface mucositis, favours hypertrophic lichen planus (95%) Other d/d lupus Clinical history of other organ involvement if lupus. Can also do DIF if fresh tissue submitted. 100

333

Lichen Planus, 100%

 

100

338

Lichen planus 100%   100

515

Lichen planus (100%)

 

100

763

Lichen Planus 100% Special stain (e.g. Grocott) for fungus 100

 

 

Qap (Anatomical Pathology AP99Q4)

[see history] [AP86][AP87][AP88][AP89][AP90][AP91]

AP87 Peer Review:  Intended diagnosis - Pemphigus vulgaris

Code

Dx

Comment

Score

123

Pemphigus vulgaris 100% Direct immunofluorescence study is important to confirm the diagnosis. A lace like pattern of squamous intercellular deposition of IgG is characteristic 100

246

Pemphigus vulgaris. 100% Immunofluorescence studies to confirm the diagnosis. 100

259

Pemphigus vulgaris 100% Direct immunofluorescence studies are very helpful in confirming the diagnosis if fresh tissue is available. IgG in the squamous intercellular substance is positive in 80 to 95% of cases 100

369

Pemphigus 100% Perform immunofluorescein study to confirm pemphigus which show intraepithelial intercellular stain of IgG and C3 95

517

Pemphigus vulgaris 100% DIF will show characteristic intercellular deposits of IgG. 100

663

Pemphigus vulgaris 100% The diagnosis can be confirmed by immunofluorence to show IgG at intercellular bridges 100

815

Pemphigus vulgaris100% Direct immunofluorescence to show intercellular IgG and/or indirect immunofluorescence for circulating IgG against the intercellular component of squamous epithelium. 100

873

Suprabasal bulla with eosinophils; consistent with pemphigus vulgaris The diagnosis has to be confirmed with immunofluorescent study and also clinical. features. 100

911

Suprabasal bullous disease suggestive of pemphigus vulgaris correlation with immunofluorescence results is required 100%

 

100

109

Pemphigus vulgaris (100%) Advise correlate with immunofluorescence findings. 100

301

Pemphigus vulgaris (70) Hailey Hailey (30) DIF to confirm diagnosis 100

333

Suprabasal bullous disease, consistent with pemphigus vulgaris, 100% Confirm diagnosis by immunofluorscence to demonstrate intercellular Ig/C3. 100

338

Pemphigus vulgaris 100% Suggest to perform direct immunofluorescence test to show IgG fluorescence of the intercellular spaces of the epidermis, if fresh frozen tissue is available. 100

448

Pemphigus vulgaris 100% To confirm by direct immunofluorescence, demonstrating intercellular IgG deposits. 100

515

Bullous pemphigus (100%) Confirmed by immunofluorescent study on frozen tissue. 90

763

Pemphigus Vulgaris 100% IF study on fresh tissue 100
Contributor's Comment
The terminology for bullous disease related to immunological defects is as follows:

Bullous pemphigoid (No detectable circulating antibodies, IgG demonstrable at the basement membrane, therefore giving rise to subepithelial vesicles or bullae).

Pemphigus vulgaris ( detectable circulating antibodies, TgG demonstrable at desmosomes at intercellular regions, therefore giving rise to intraepithelial vescicles/bullae).

No such terminology of bullous pemphigus.

 

Qap (Anatomical Pathology AP99Q4)

[see history] [AP86][AP87][AP88][AP89][AP90][AP91]

AP88 Peer Review:  Intended Diagnosis: Seminoma

Code

Dx

Comment

Score

123

Seminoma 100%

 

100

246

Seminoma. 100% Await paraffin section to look for features of atypical seminoma. 100

259

Seminoma 100%

 

100

369

Seminoma 100%

 

100

517

Seminoma 100%

 

100

663

Seminoma 100% Immunohistochemistry is positive for PLAP 100

815

Malignant lymphoma 70% Seminoma 30% Discohesive pattern suggests a lymphoid malignancy with rare Reed-Sternberg-like cells. Non-Hodgkin'slymphoma and Hodgkin's disease need to be excluded with lymphoid markers. Though not typical of seminoma thisremains a diagnostic consideration. Perform immunostains for lymphoid markers, placental alkaline phosphatase and alpha-fetoprotein if frozen / permanent sections are not diagnostic. 60

873

Conventional seminoma 100% No trophoblast-like cells seen 100

911

Malignant tumour favour seminoma. Classical type. Suggest correlation with frozen section slide 100%

 

100

109

Seminoma (100%)

 

100

301

Seminoma, classical type (95%) Malignant lymphoma Immunoperoxidase stains for placental alkaline phosphatase for seminoma. Lymphoid markers (in cytologically malignant cells)if lymphoma 100

333

Seminoma, 100% Examine frozen section and further sampling to look for other germ cell tumor component. 100

338

Seminoma 100% Other type of germ cell tumor is not seen on the imprint smear. Suggest additional paraffin sections to look for possibility of mixed germ cell tumor. 100

448

Seminoma 100% Correlate and confirm with the frozen section and subsequent paraffin section. 100

515

Germ cell tumour, favour seminoma (90%) Paraffin and additional section to exclude mixed germ cell tumour. e.g. component of embryonal carcinoma. 100

763

Seminoma, classic (pending H/E stained on frozen tissue) 100% Adequate sampling to rule out non-seminomatous germ cell component 100

 

 

Qap (Anatomical Pathology AP99Q4)

[see history] [AP86][AP87][AP88][AP89][AP90][AP91]

AP89 Peer Review:  Intended Diagnosis- Acute paracetamol (acetaminophen) hepatotoxicity

Code

Dx

Comment

Score

109

Centrilobular necrosis and microvesicular steatosis (100%) Advise confirm presence of steatosis with fat stain on frozen section. Microvesicular steatosis together with the clinical history suggest Reye's syndrome. Biochemical tests to exclude disorders of fatty acid oxidation such as carnitine deficiency should be performed as they can closely mimick Reye's syndrome. The presence of centrilobular necrosis is unusual but can be terminal event. However other causes such as paracetamol overdose needs to be excluded as well. 80

123

Acinar zone 3 necrosis Paracetamol poisoning has to be ruled out. Correlation with clinical history is required. Metabolic diseases should also be considered. Fresh frozen liver tissue should be kept for possible further study. 100

246

Zonal (zone 3&2) liver cell necrosis. 100% Morphological features do not supportReye's syndrome. Need clinicopathologic correlationfor the cause of the zonal necrosis. Considerationshould be given to adverse reaction to drug,particularly paracetamol, and inherited metaboicdisease (by careful review of the family history andappropriate biochemical and ultrastructural 100

259

Submassive zone 3 hepatic necrosis with micorvesicular fatty change and cholestasis. Differential diagnosis include drug induced (90% )and Reye's syndrome(10%) Drug history is important, particularly paracetamol (fro drug induced) and aspirain (for Reye's Syndrome) 90

301

Acute shock liver (ischaemic hepatitis) No features of Reye's syndrome. Some hepatocytes with fine vacuoles in the cytoplasm - ?possibility of metabolic disease. Was any tissue frozen for metabolic studies? 10

333

Acinar zone 3 necrosis and microvesicular fatty change, Differential diagnoses: Reye's syndrome, 50% Drug-induced hepatitis 50% 1) Correlate with drug history/ serum drug level 2) Lipid stain on frozen section to demonstrate fat in Reye's syndrome 3) Exclude viral infection (serology + EM), and inborn error of metabolism e.g. medium chain acyl-coA dehydrogenase deficiency. 80

338

Diffuse zone 3 hepatocellular necrosis without significant inflammatory reaction, probably drug related. 100% The section shows diffuse zone 3 necrosis without inflammatory reaction. There is no fatty change in hepatocyte to support the diagnosis of Reye's syndrome. No viral inclusion seen. The morphology and the pattern of necrosis is consistent with Acetaminophen intoxication and other drugs. Please correlate with the history and other clinical finding. 100

369

Zone 3 necrosis and fatty change. DDx include Reye's and Rye's-like sybdeomes 100% Suggest clinical correlation and perform investigations to see if there is any metabolic diseases or infection which may give rise to Reye's-like syndrome 10

448

Reye's syndrome 50% Other viral infections, drug effects 50% Classical Reye does not produce cholestasis and zonal(3)necrosis, both of which were noted in this case. Have to correlate with clinical history ( most importantly drug history ), and viral and serology findings. 80

515

Centrilobular necrosis (zone III necrosis) (100%) No viral inclusion found. Suggest clinical correlation for drug history and toxicology for drug level, e.g. paracetamol. 100

517

Microvesicular steatosis, consistent with Reye's syndrome 100% Need to exclude in-born error of metabolism as an underlying cause 10

663

1. Zone 3 necrosis, caused by drug e.g. paracetamol or toxin 80%2. Zone 3 necrosis, caused by viral infection 20% Correlate with clinical history and viral culture result 80

763

Submassive necrosis of Liver (acute stage) 100% Addition/Revision to the previous submission: Clinical features are compatible with Reye's syndrome. However, fatty change is not obvious and necrosis if occurs in Reye's syndrome is usually periportal (zone 1) rather than centrilobular (zone 3) as in this case. To support the diagnosis of Reye's syndrome: fat stain on fresh frozen tissue section (look for microvesicular steatosis which might not be apparent on H/E stain) and EM study (for mitochondrial changes) are required. Alternatively, inborn error of metabolism, viral infection, drug or chemical induced toxity or shock should also be considered. It is prudent to bear in mind that multiple aetiological factors and pathological processes might be in operation in producing the final histological picture seen. 50

815

Submassive hepatic necrosis consistent withFulminant Reye's syndrome 100% The histology is not classical of Reye's syndrome. Oil-red-O stain on frozentissue and EM will confirm Reye's syndrome microvesicular fat and typical mitochondrial changes are seen. Other causesof submassive necrosis -- viral hepatitis, drug-induced, toxic or metabolic injury should be excluded with additional historyand ancillary investigations for hepatotropic viral markers. 50

873

Centrilobular coagulative necrosis 100% Acute acetaminophen toxicity has to be excluded . Complete with toxicology findings. Frozen section with fat stain will help to settle clinical suspicion of Reye's syndrome 100

911

Submassive centrilobular necrosis possible caused include drug e.g. paracetamol overdose ans schock 100%

 

50

Scoring Scheme:

Most participants correctly spotted the pathology but have difficulties in pinpointing the likely etiologic process. The clinical implication is of major significance. The marks are stratified according to the confidence level of making a diagnosis of drug hepatotoxicity. Marks are deducted for those (109, 259, 333, 448, 815) who considered Reye’s syndrome was a valid histologic differential diagnosis.

CME Section:

The possibility of toxic liver injury was explained to the paediatrician after the paramortem liver biopsy and postmortem examination. The plasma paracetamol concentration was subsequently checked on saved serum and was found to be at the toxic level.

The histologic features in the slide is characteristic of acute paracetamol hepatotoxicity (about day 5-7 for the present case). There are extensive centrizonal and midzonal liver cell necrosis. Pale eosinophilic structures consistent with remnants of dead hepatocytes are present in the liver cell cords. These necrotic cell remnants suggest ischemic coagulative necrosis with preservation of cell cytoplasm and nuclear outline, however, the granular and distorted appearance is more prominent than the usual uncomplicated ischemic necrosis. Furthermore, surviving hepatocytes show features of damage and reactive changes such as microvesicular steatosis, cellular swelling and prominent nucleoli. The endothelial cells are preserved and swollen. Vascular congestion is not particularly prominent. Zonal necrosis is not a feature in Reye's syndrome and the hepatocytes are not toxic looking. Besides clinical jaundice is most unusual. Coagulative necrosis caused by non-hepatotrophic viral infection (eg herpes simplex virus, adenovirus) is of irregular distribution, and viral inclusions can be easily found. This is not the type of necrosis seen in viral hepatitis, in which inflammatory infiltrate would be expected to be prominent.

The list of drugs and compounds that may be associated with centrizonal and midzonal necrosis is extensive. The most frequent and classical examples are paracetamol, toxin of the mushroom Amanita phalloides and carbon tetrachloride. They may show different patterns of steatosis. Steatosis is absent or mild centrilobular, microvesicular in paracetamol toxicity. (MST)

 

 

Qap (Anatomical Pathology AP99Q4)

[see history] [AP86][AP87][AP88][AP89][AP90][AP91]

AP90 Peer Review:  Intended Diagnosis - Adenocarcinoma

Code

Dx

Comment

Score

123

Malignant cells present, consistent with metastatic adenocarcinoma 100% If cell block is available, immunostains for CEA, EMA, BerEP4, LeuM1 can be performed to to confirm the diagnosis 100

246

Adenocarcinoma. 100% Particular primary tumors to beconsidered, among many others, are breast, lung andovary. 100

259

Metastatic adenocarcinoma 100% History of primary carcinoma elsewhere is important. Immunohistochemical studies using BerEP4, CEA, calretinin, LeuM1 and CK 5/6 may be useful. BerEP4, CEA or LeuM1 positivity supports a diagnosis of adenocarcinoma while positivity of calretinin and CK 5/6 suggests mesothelioma. 100

369

Malignant cells present DDX between adenocarcinoma and malignant mesothelioma 100% Perform mucicarmine, PASD histochemical stain and CEA, LeuM1 immunostain for adenocarcinoma, calretinin immunostain for mesothelial differentiation. 80

517

Adenocarcinoma To be confirmed with a panel of imunomarkers (CEA, LEU-M1, BerEP4) 100

663

Adenocarcinoma cells seen 100% The possible primary site includes lung, breast and ovary 100

815

Adenocarcinoma 100% Exclude primaryadenocarcinoma of lung, breast, genital organs and GI tract and perform immunostaining with Ber-EP4, CEA, HBME-1and calretinin to exclude malignant mesothelioma. 100

873

Malignant cells: consistent with adenocarcinoma 100% Immunohistochemistry may be helpful to delineate the primary, if clinically, the primary site is unknown. 100

911

Metastatic adenocarcinoma 90%Mesothelioma 10% Suggest histochemical staining (PAS, MC, alcian blue + hyalurondase and immunohistochemical staining (CEA, BerEP4, LeuM1) for confirmation. 100

109

Adenocarcinoma (100%) Advise immunohistochemical stain for confirmation. 100

301

Positive for malignant cells Adenocarcinoma (70) Mesothelioma (30) History of previous primary? Immunoperoxidase stains required if no relevant history 80

333

Malignant cells seen, Adenocarcinoma 95% Mesothelioma 5% Perform immunostaining for CEA, BerEP4 (positive in adenocarcinoma) and Calretinin (positive in mesothelioma) 100

338

Malignant cells present, consistent with Adenocarcinoma. 100%

 

100

448

Malignant cells present, metastatic adenocarcinoma 100% To look for primary tumour in either breast or lung or others 100

515

Metastatic adenocarcinoma (>95%), mesothelioma (<5%) Comment: To be confirmed by immunostaining for CEA, BerEp4 and calretinin. Possible primary site in ovary, lung and breast (if adenocarcinoma is confirmed).

 

100

763

Malignant cells present, favour adenocarcinoma over mesothelioma 100% Detail clinical history and correlation with CT/radiological findings. Immunohistochemical studies for mesothelial and glandular markers; CK7 and CK20 for origin of the malignancy (if adenocarcinoma). EM study (if materials available) if IH results are inconclusive or indicative of mesothelioma. 100

 

 

Qap (Anatomical Pathology AP99Q4)

[see history] [AP86][AP87][AP88][AP89][AP90][AP91]

AP91 Peer review:  Intended Diagnosis - Proliferative fibrocystic disease

Code

Dx

Comment

Score

123

Fibrocystic disease with sclerosing adenosis 100%

 

100

246

Complex sclerosing lesion, with floridepithelial hyperplasia (90%).Above + Focal atypical ductal hyperplasia (10%). Comment: Extensive sampling should be done forhistological study. Need to correlate with clinicaland radiological findings. If all three correlatewell, clinical follow up should be sufficient. If there is any suspicion, re-excision is advised. 100

259

Proliferative fibrocystic change with sclerosis adenosis and moderate epitheliosis. The changes indicate a slightly increased risk (x2) for invasive carcinoma 100

369

Sclerosisng adenosis 100%

 

100

515

Fibrocystic change, benign (100%)

 

100

517

Sclerosing adenosis with moderate epithelial hyperplasia 100%

 

100

663

1.Fibrocystic change (with florid epitheliosis, apocrine metaplasia, cysts and mucoceles, adenosis with clear cell hyperplasia, columnar alteration with prominent apical snouts and secretion). Benign calcification. The change is associated with a mild increased risk (1.5x) of developing invasive carcinoma compared with the risk in the general population. 100

815

Proliferative fibrocystic change with florid ductalhyperplasia 100% Smooth muscle actin stain highlights myoepithelial cells in the proliferating ductular lesions.No atypia is observed in this section, but additional blocks of the lesion should be examined. Follow-up is warranted because of slighly increased risk. 100

873

Benign breast lesion with florid epitheliosis and sclerosing adenosis. 100%

 

100

911

Fibrocystic disease, sclerosing adenosis and florid epithelial hyperplasia 100%

 

100

109

Benign, proliferative fibrocystic changes including sclerosing adenosis, florid epitheliosis, apocrine metaplasia, fibrosis and cysts (100%) There is a slight increase in risk (x2) for invasive carcinoma 100

301

Atypical ductal hyperplasia and atypical papillary apocrine hyperplasia bordering on DCIS DO 34BE12 to exclude DCIS 80

333

Proliferative fibrocystic disease (epitheliosis, apocrine metaplasia, microscopic papilloma, with microcalcification, 95% Atypical hyperplasia 5%

 

100

338

Fibrocystic changes, with Sclerosing adenosis. 100% The presence of Sclerosing adenosis in proliferative fibrocystic changes indicate a slightly increased risk ( x1.5 - 2 ) for invasive carcinoma. 100

448

Breast proliferative disease without atypia; fibrocystic change 100% Nil 100

763

Fibrocystic change with sclerosing adenosis and epithelial hyperplasia 100%

 

100