General Pulm Path Flashcards
Lymphangiomyomatosis
Associated with tuberous sclerosus complex (TSC1 or TSC2 genes). Classically occurs in females with TSC (~85% of females with TSC develop pulmonary LAM, while only ~20% of males with TSC will).
Histologically, looks like slightly bubbly smooth muscle filling lymphatic spaces. There is no atypia, mitosis, or necrosis.
Classified as an intermediate grade neoplasm (low grade, metastasizing, locally destructive).
Associated with bilateral upper and lower lobe cysts, often complicated by recurrent pneumothorax.
On IHC, positive for smooth muscle markers (desmin), as well as HMB-45. If you are unsure, throw a desmin on. True LAM will light up.
In the context of a history of recurrent pneumothorax
The classic bleb and scar.
Lung with (focal) bleb formation and subpleural scarring, consistent with recurrent pneumothorax.
This is how to write it up, but you have to look for 3 things that could underly your recurrent pneumothorax:
1. Lymphangiomyomatosis
2. Britt-Hogg-Dube syndrome
3. Cancer
Brit-Hogg-Dube syndrome
Mutation in FLCN, encoding the protein folliculin, a GAP that regulates the mTOR and TFE3/TFEB pathways.
Tumor syndrome that also manifests with multiple bilateral upper and lower lobe pulmonary cysts, often complicated by recurrent pneumothorax.
Associated tumors include:
Fibrofolliculomas of the skin
Trichodiscomas of the skin
Chromophobe RCC
Hybrid chromophobe/oncocytomas
Conventional RCC
Lymphangioleiomyomatosis in a lymph node
Can create a “dermatopathic” lymph node appearance.
Multilocular thymic cyst
Multilocular thymic cyst is a reactive process that may be seen in response to specific infections such as HIV or in the setting of neoplasms arising in thymus including, nodular sclerosis Hodgkin lymphoma, thymoma, seminoma, yolk sac tumor, or lymphoma.
Histologic examination shows variably-sized cysts lined by flattened epithelium. The surrounding stroma contains lympho-plasmacytic inflammatory infiltrate. Some cases may show cuboidal, ciliated, columnar, or squamous epithelium. Fibrosis is also usually present. Other findings that may be encountered include cholesterol granulomas and pseudoepitheliomatous hyperplasia.
Sclerosing mediastinitis (aka calcifying fibrous pseudotumor)
Histologically characterized by dense fibrosis, a polymorphic inflammatory infiltrate with abundance of plasma cells, and dystrophic calcification.
Many cases of chronic mediastinitis are caused by Histoplasma or Mycobacteria. In many cases, no cause can be ascertained (idiopathic sclerosing mediastinitis).
You must technically rule out IgG4-related sclerosing mediastinitis to diagnose idiopathic.
Thymic hyperplasia
True thymic hyperplasia is defined as increase in both size and weight of the gland while maintaining normal architecture.
It may be 1) idiopathic (extremely rare), 2) may be seen as a rebound phenomenon during recovery from a stressful event such as steroid therapy or chemotherapy for malignant tumor and 3) in association with endocrine abnormalities, sarcoidosis, and Beckwith-Wiedeman syndrome.
Thymic follicular hyperplasia is present in about two-thirds of patients with myasthenia gravis. It has also been associated with hyperthyroidism, lupus, Addison’s disease, early stages of HIV infection and other immune-related diseases.
How to think about thymomas
Thymomas are epithelial neoplasms with varying degrees of thymocyte recruitment. These thymic epithelial cells may be epithelioid or spindled.
Immature thymocytes are TdT+, CD99+, CD1a+.
Large or old thymomas may undergo hemorrhage, necrosis, or cystic change. Cysts may have a pseudoglandular appearance.
Type A thymoma (aka spindle cell thymoma)
~10% of thymomas, mean age ~65.
May present with myasthenia gravis, or may present with obstructive symptoms (dyspnea, chest pain, persistent cough) and B symptoms.
Composed of bland spindle or oval epithelial cells admixed with few or no lymphocytes. Generally have a thick fibrous capsule as shown here. Prominent fibrous bands course through the tumor separating it into lobules. A few scattered lymphocytes/thymocytes may be present, but do not compose the bulk of the tumor.
May display a variety of architectural patterns, including microcystic foci, rosettes, glandular structures, meningioma-like whorls, storiform pattern, and hemangiopericytoma-like vascular areas. Multiple pattern are seen within the same tumor. Cells have oval or round bland nuclei with finely dispersed chromatin and inconspicuous nucleoli.
If significant lymphoid aggregates are present or comprise more than 10% of the tumor, this is better diagnosed as type AB thymoma.
Stage I: Completely incapsulated
Stage II: Capsular invasion or gross invasion
Overall, prognosis of Type A thymoma is excellent, with a 90% 5 year survival rate and 80% 10 year survival rate.
IHC: Thymic epithelial markers (PAX8, FOXN1, CD205+)
Type AB thymoma (Mixed type)
~30% of thymomas
May present with myasthenia gravis, or may present with obstructive symptoms (dyspnea, chest pain, persistent cough) and B symptoms. Rarely, may present with pure red cell aplasia.
Histologically, divided into lymphocyte-rich type B areas and lymphocyte-poor type A areas. The proportion of A to B varies highly from tumor to tumor. Sometimes regions have intermixed type A and type B components.
Unlike type B1 thymoma, there are no Hassall corpuscles.
The prognosis for type AB thymoma is excellent.
Masaoka-Koga Classification System for the staging of thymomas
Stage I: Completely encapsulated grossly and microscopically.
Stage II: Microscopic capsular invasion (Stage IIa) OR macroscopic invasion into thymic or surrounding adipose tissue, or gross adhesions to but no invasion of pleura or pericardium (Stage IIb).
Stage III: Macroscopic invasion into surrounding structures (lung, pericardium, great vessels).
Stage IV: Pleural or pericardial metastases (Stage IVa) OR distant metastases via lymphoid or hematogenous route (Stage IVb).
Type B1 thymoma (lymphocyte rich thymoma)
~20% of thymomas, most commonly seen in 40-60 year old women
Histologically, this subtype most resembles the normal thymus. It is usually an encapsulated mass with fibrous bands separating it into nodules or lobules. It has areas resembling normal thymic cortex which are composed of scattered epithelial cells in a dense background of immature T-cells.
The low power appearance is that of a predominance of dark blue cortical areas and a few pale islands of medullary differentiation, which may or may not have Hassall’s corpuscles.
The cortical areas are composed of scattered neoplastic epithelial cells in a background of a dense infiltrate of non-neoplastic immature T-cells. The presence of tingible-body macrophages surrounded by densely packed lymphocytes has created a starry-sky appearance.
The neoplastic epithelial cells in type B1 thymoma are scattered singly in a background of densely-packed non-neoplastic immature T-cells. They are difficult to appreciate at low magnification. The epithelial cells have pale eosinophilic cytoplasm with ill-defined cytoplasmic borders, uniform round to oval vesicular nuclei, and variably-prominent nucleoli.
T lymphoblastic lymphoma is a major differential diagnosis, but lacks CK19+/p63+ epithelial cells. If the epithelial cells are increased in number or form clusters (3 or more cells), the diagnosis of type B2 thymoma should be considered.
The epithelial component in type B1 thymomas is diffusely positive for CK19, p63, and PAX8. They are focally positive for CK7, CK8, CK14, and CK18. They are negative for CK20.
The cortical areas are composed predominantly of a dense infiltrate of immature T-cells which are TdT+, CD1a+, CD3+, CD4+, CD8+, and CD34-ve.
The medullary islands contain mature T-cells which are CD3+, TdT-ve, CD1a-ve, and either CD4+ or CD8+. There are also mature B-cells which express CD20 and CD79a. The epithelial cells in medullary islands are diffusely positive for CK19.
Type B1 thymoma is a tumor of low-grade malignant potential. Prognosis is quite good, but recurs in 10-15% of cases.
Type B2 thymoma
~25-30% of thymomas
~55% of case associated with myasthenia gravis (highest among the thymomas).
Histologically, composed of clusters of neoplastic epithelial cells in a background of abundant immature T-cells. Foci of medullary differentiation may or may not be seen. There are often thick, fibrous bands dividing the tumor into lobules.
The tumor appears basophilic due to abundance of lymphocytes which are predominantly immature T-cells. Within this rich lymphocytic infiltrate, there are polygonal epithelial cells scattered singly or in small clusters. The epithelial cells have round or oval vesicular nuclei with punctate nucleoli. Anaplastic features may be focally present.
The epithelial density is higher than that of B1 thymoma, but there are no confluent, solid sheets of epithelium, as in type B3 thymoma.
Type B2 thymomas are more likely to invade beyond capsule into the surrounding fat or mediastinal structures as compared to thymomas type A, type AB, or type B1. They are more likely to present at a higher stage.
Type B3 thymoma
~15-20% of thymomas, most often in patients in their 50’s-60’s with slight male predominance.
Histologically, the tumor has a lobular architecture with coarse or delicate fibrous bands dividing the tumor into irregular lobules. At low power, the tumor has a pink appearance due to predominance of neoplastic epithelial cells arranged in solid sheets. The epithelial cells often show perivascular palisading (shown). A small number of non-neoplastic lymphocytes, usually immature T-cells, are sprinkled in the background.
Abortive Hassall’s corpuscles may be present.
Neoplastic epithelial cells are polygonal and contain moderate amount of eosinophilic or clear cytoplasm. The nuclei are round, oval, or irregular and may show prominent nucleoli. Focal anaplastic changes may also be seen.
Poorest prognosis of all thymomas. Tend to present at an advanced stage.
Abortive Hassall’s corpuscle
Suggests type 3 thymoma
Looks like a phyllodes, huh?
Beware! Sometimes a non-chondroid pulmonary hamartoma can have this appearance due to entrapped airways. They may contain small foci of cartilage, which can assist in diagnosis, but this won’t always be the case.
Pulmonary hamartoma without areas of chondroid change
Carcinoid tumorlet
Small proliferations of lung neuroendocrine cells which, by definition, measure less than 5mm.
Most commonly associated with bronchiectasis, parenchymal scarring, or peripheral carcinoid tumors.
Cellular NSIP, or “cellular chronic interstitial pneumonia”
Clinical ddx includes idiopathic NSIP, HP, CTD-ILD, drug toxicity.
May or may not be associated with organizing pneumonia. Significant lymphocytic infiltrate supports HP or CTD-ILD. If granulomas are present, this favors HP.
Lymphoid interstitial pneumonia
Rare interstitial pneumonia that is most commonly associated with underlying immunodeficiency or CTD.
Densely cellular chronic interstitial pneumonia composed of lymphocytes and plasma cells in variable proportions, sometimes accompanied by histiocytes and loose granulomas. Marked widening of alveolar septa by the infiltrate with compression and distortion of alveolar spaces is a characteristic distinguishing feature. Associated proteinaceous fluid often fills the alveolar spaces.
Before making this diagnosis, be sure to consult with hematopathology to rule out a low-grade MALT lymphoma.
Tends to affect middle-aged adults. Onset in children should raise the concern for possible HIV/AIDS.
This entity is on a disease continuum with follicular bronchiolitis.
Fibrotic NSIP
Relatively diffuse, uniform-appearing interstitial fibrosis without significant architectural distortion (scarred or honeycomb areas). Temporal uniformity (usually no fibroblastic foci). Mild-to-moderate associated chronic inflammation. Occasional small foci of organizing pneumonia.
Note that you can have NSIP-like areas in UIP, as UIP should have temporal heterogeneity and some areas will look like mature NSIP fibrosis.
