Unknown Slide Case 2009

WISCONSIN SOCIETY OF PATHOLOGISTS
2009 ANNUAL MEETING

TV Colby MD
November 21, 2009

Case Histories

CASE 1:
Clinical History: 52M was found to have radiologic abnormalities on routine chest x-ray. CT showed calcified mass in right apex and small calcified mass in left apex, mediastinal adenopathy with multiple calcified nodes. PET scan weakly positive in hilar nodes. On re-questioning, he had experienced some exertional dyspnea.

Work history: 36 years at a company where he was exposed to aerosolized material including silica-based casting coating, aluminum-based coating, and others.

CASE 2:
Clinical History: 64M two months status-post bilateral lung transplant for refractory MAI infection and COPD.
Was found to have new bilateral pulmonary nodules.

Past history: Large-cell lymphoma in remission for 7 years.
One of the lower lobe nodules was resected for diagnosis.

CASE 3:
Clinical History: History: 43F who presented with recurrent hemoptysis. Radiologically there were multiple bilateral poorly-defined nodules, some cavitated.

Prior history: Hereditary pulmonary telangectasia with AVM’s.

CASE 4:
Clinical History: 58M with progressive dyspnea over several months.

Radiology: Bilateral ground glass opacities and “fibrotic changes on CT.” Biopsies taken from lower lobe, upper lobe, and lingula.

CASE 5:
Clinical History: 49F with chest pain. Right upper lobe mass identified radiologically (5.0 cm diameter). Right upper lobectomy performed.

CASE 6:
Clinical History: 50M, nonsmoker with gradually enlarging lung nodules over 5 years. Most were small than 1 cm and distributed bilaterally (RUL, RML, LUL).

CASE 7:
Clinical History: 51M with dyspnea worsening over the past year.
Former smoker; exposed to paints.

CT: bilateral hilar adenopathy and increased interstitial pattern with opacification in the mid and lower lung fields.
Clinically sarcoidosis suspected.

Download
WSOP Slide Seminar
TV Colby MD
Nov.21, 2009

PowerPoint Presentation (45.4mb)

CASE HISTORY 1

CASE 1: TV09-397 (S09-15216)
Clinical History: 52M was found to have radiologic abnormalities on routine chest x-ray. CT showed calcified mass in right apex and small calcified mass in left apex, mediastinal adenopathy with multiple calcified nodes. PET scan weakly positive in hilar nodes. On re-questioning, he had experienced some exertional dyspnea.

Work history: 36 years at a company where he was exposed to aerosolized material including silica-based casting coating, aluminum-based coating, and others.

Diagnosis:
Macular and nodular histiocytic infiltrates consistent with (cellular) silicosis with some early fibrotic nodules.

Does this patient have a pneumoconiosis?
You need more than histology alone.

Silicosis Key Features

Sheets of histiocytes along lymphatic routes
Absence of sarcoid-like granulomas
Fibrous nodules
Birefringent material may not knock your socks off
And of course………the history

CASE HISTORY 2 TV09-398

Clinical History: 64M two months status-post bilateral lung transplant for refractory MAI infection and COPD.
Was found to have new bilateral pulmonary nodules.

Past history: Large-cell lymphoma in remission for 7 years.
One of the lower lobe nodules was resected for diagnosis.

Immunohistochemical Evaluation

Positive: CK 7, CK 20, PLAP (scattered), HCG
Negative: CK 5/6, TTF-1, vimentin, CG, Syn, CA19-9, PSAP, PSA, CD30, EMA, CD117, AFP, ALK-1, CD3, CD20

Diagnosis:
Necrotic hemorrhagic poorly differentiated carcinoma, ?metastatic, with germ cell differentiation.

Additional Evaluation:
To assess origin of the neoplasm (recipient vs. allograft/donor; performed at CompGene).

“Molecular finger printing showed that the DNA isolated from the 2 samples were genetically non-identical at all 4 loci tested. These data are consistent with the 2 DNA samples arising from 2 different individuals.”

This suggests the malignancy was of donor origin!

Additional Questions:
Any available information on the donor?

Was there any non-neoplastic lung tissue from this or prior specimens that could be an additional control sample?.

CASE HISTORY 3 TV09-399 (08-2207)

Clinical History: History: 43F who presented with recurrent hemoptysis. Radiologically there were multiple bilateral poorly-defined nodules, some cavitated.

Prior history: Hereditary pulmonary telangectasia with AVM’s.

Diagnosis:
Wegener’s granulomatosis with associated alveolar hemorrhage, including capillaritis and granulomatous foci with necrosis and microabscess formation.

No AVM’s seen.

Capillaritis is common in DAH – Lung capillaritis is analogous to leukocytoclastic vasculitis – Capillaritis is not specific – Capillaritis is not a disease

Capillaritis in WG-related DAH – Collagen type IV stain

Pulmonary Vasculitis Syndromes
Pulmonary vasculitis is most commonly an ANCA-associated small vessel vasculitis:

Wegener’s granulomatosis (WG) Microscopic polyangiitis (MPA) Churg-Strauss syndrome (CSS)

Among these WG is most common

ANCA-Associated Vasculitis in the Lung

WG: 90% ANCA positive (c >> p)
MPA: 80% ANCA positive (p > c)
CSS: 70% ANCA positive (p > c)

WEGENER’S GRANULOMATOSIS
Presentation in the Lung

Alveolar hemorrhage syndrome

Parenchymal consolidation/nodule formation with or without cavitation

Pathology of WG

WG is an inflammatory disease that is more than a vasculitis

Pathology of WG can be grouped as:
    Vasculitis (including capillaritis)
    Necrosis (granulomatous with giant cells)
    Inflammatory background

Features vary from case to case

Pathological Differential Diagnosis of WG

Nonspecific inflammatory lesions
Alveolar hemorrhage syndromes
Granulomatous infections
Other vasculitic syndromes
Other angiitis and granulomatosis
Miscellaneous (RA, dirofilarial nodules)

Diagnosis of Wegener’s Granulomatosis

Negative cultures and special stains*
Clinicopathologic with additive effects of:

Clinical findings and sites of disease
Histologic levels of confidence
Results of c-ANCA
How sick?

Basic decision is whom to treat with potentially toxic therapy

CASE HISTORY 4 TV09-400 (09-3480)

Clinical History: 58M with progressive dyspnea over several months.

Radiology: Bilateral ground glass opacities and “fibrotic changes on CT.” Biopsies taken from lower lobe, upper lobe, and lingula.

Diagnosis:

LUL: Granulomatous interstitial pneumonia ? hot tub lung, ? sarcoid (or infection), doubt HP.
Lingula: Patchy organizing pneumonia, occasional granulomas, foci consistent with UIP.
LLL: UIP plus scattered granulomas

Issues:

2 diseases or 1?
I favor UIP (idiopathic pulmonary fibrosis) plus a granulomatous process?
How to sort out?

Cultures
History
Review HRCT
Follow-up

CASE HISTORY 5 TV09-401 (09-6257)

Clinical History: 49F with chest pain. Right upper lobe mass identified radiologically (5.0 cm diameter). Right upper lobectomy performed.

Diagnosis:

Morphologic changes consistent with IgG4-related lung disease.
Elevated serum IgG4?
Pancreatic disease?
Other disease?

Hyper-IgG4 Disease: Synonyms

IgG4-related sclerosing disease
Hyper-IgG4 disease
Multifocal systemic sclerosis
Multifocal systemic fibrosclerosis
Autoimmune pancreatitis (AIP)
Et.al.

Hyper-IgG4 Disease

First recognized as an inflammatory process of the pancreas simulating carcinoma:
Named autoimmune pancreatitis (AIP)
List of affected sites increasing:
biliary tract, liver, salivary gland, orbit, lung, kidney, prostate, breast, aorta, pituitary, retroperitoneum, trachea/bronchi, bone marrow, lymph node, stomach, brain, mesentery, thyroid, mediastinum, pleura, et al.

Pulmonary Histopathology in IgG4-Positive Disease: Results (Shrestha, et al.)

Significant increase in IgG4-positive plasma cells (2+ or 3+) in the following:

6/6 AIP cases
12/12 lung diseases resembling AIP
6/8 Rosai-Dorfman disease
4/10 inflammatory myofibroblastic tumors

“Background” IgG4 Cells in the Lung

93 cases evaluated; variety of histologies
31 cases showed IgG4-positive plasma cells in the infiltrate
In 14 of the 93, the IgG4 score was 2 or 3: 2 UIP, 3 NSIP, 1 nonspecific pleuritis, 1 rheumatoid nodule, 4 inflammatory myofibroblastic tumor (40% of the cases), 1 organizing pneumonia, 1 DAD, 1 necrotizing granuloma.

Pulmonary Histopathology in IgG4-Positive Disease:
Conclusions (Shrestha, et al.)

IgG4 disease can present primarily in the lung
The nature of extranodal Rosai- Dorfman disease is questioned
IgG4+ plasma are uncommon in inflammatory lung diseases

Hyper-IgG4 Disease:
Distinctive Lung Histopathology

Mixed inflammatory infiltrates in lymphatic distribution
Vascular infiltration, especially veins
Bronchiolar infiltration
S-100-positive histiocytes with emperipolesis
Plasma cell infiltrates (↑IgG4+ cells) with associated fibrosis
Some cases with prominent eosinophils and germinal centers

Hyper-IgG4 Disease

An expanding spectrum of involvement which includes the lung
Is this a disease or an immunologic marker common to a number of diseases?
What has this been called in the past?
LYG, LIP, NSIP, Inflammatory myofibroblastic tumor/IMT (inflammatory pseudotumor, plasma cell granuloma), lymphoid hyperplasia, descriptive, et. al.

CASE HISTORY 6 TV09-402 (09-17108)

Clinical History: 50M, nonsmoker with gradually enlarging lung nodules over 5 years. Most were small than 1 cm and distributed bilaterally (RUL, RML, LUL).

Diagnosis:

Morphologic changes consistent with IgG4-related lung disease.
Consistent with nodular lymphoid hyperplasia
Is MALTOMA ever excluded?

Extranodal Marginal Zone B-Cell Lymphoma of Lung: Histology

Lymphocytes
Monocytoid/centrocytic cells
Transformed cells
Plasma cells
Plasmacytoid cells (± Dutcher bodies)
Lymphoepithelial lesions
Granulomas
Sclerosis
Amyloid
Crystal storing histiocytosis
Germinal centers

CASE HISTORY 7 TV09-403 (09-23681)

Clinical History: 51M with dyspnea worsening over the past year.
Former smoker; exposed to paints.

CT: bilateral hilar adenopathy and increased interstitial pattern with opacification in the mid and lower lung fields.
Clinically sarcoidosis suspected.

Diagnosis:

Fibrosing interstitial pneumonia most consistent with usual interstitial pneumonia associated with granulomas, ? sarcoidosis as an additional diagnosis.
Chronic sarcoid for comparison…