W4L5 - Malignant Metastatic Effusions Flashcards
Metastatic Effusion
When cancer grows in the pleural space (for example), it causes a malignant pleural effusion
This condition is a sign that the cancer has spread, or metastasized, to other areas of the body
Identifying Malignancy in Effusions
Two stage process:
1. To establish a malignancy (benign or malignant)
2. Determine the phenotype (mesothelioma vs metastatic malignancy)
Most malignant effusions need to be differentiated into two major categories:
1. Malignant mesothelioma
2. Metastatic adenocarcinoma
Low Power Clues for Metastatic Effusions
Evidence of 2 populations of cells Large cohesive aggregates and clumps of cells Papillary formations Acinar formations Proliferation spheres Solid cell clusters Non-cohesive cell clusters
Incidence of Serous Membrane Involvement in Pleural and Peritoneal Cavities - Female
Pleural: - breast - ovary - lung - haematolymphoid Peritoneal: - ovary - breast - GI tract - pancreatobiliary
Incidence of Serous Membrane Involvement in Pleural and Peritoneal Cavities - Males
Pleural: - lung - haematolymphoid - genitourinary - GI tract Peritoneal: - haematolymphoid - GI tract - genitourinary - pancreatobiliary
Incidence of Serous Membrane Involvement in Pleural and Peritoneal Cavities - Children
Pleural: Leukemia/lymphoma Small round cell tumours - neuroblastoma - nephroblastoma Peritoneal: Leukemia/lymphoma Small round cell tumours Others
Identification of Malignancy in Effusion
Diagnosis of malignant effusions incorporate large amounts of criteria, some subtle, including the familiarity of the type of specimen your reviewing, the type of preparation and the context in which the diagnosis is being made
- diagnosis of malignancy in effusion samples does not depend on any single morphologic criteria
- cytology does not depend on large cells, with high N/C ratio, hyperchromatic, irregular nuclei and macronucleoli
Metastatic Adenocarcinoma
These are by far the most common metastatic malignancy found in serous effusions
This differentiation is dependant upon certain morphologic features associated with adenocarcinoma, taking into consideration the sex of the patient, age and site of the effusion samples
The most common metastatic adenocarcinomas in serous effusions originate from neoplasms of breast, lung, haematolymphoid and ovary
Classically, the cells from these lesions show:
- cellular specimens
- smoothly contoured cohesive aggregates
- containing large cells with eccentric nucleoli and vacuolated cytoplasm
Metastatic Adenocarcinoma - Cell Clusters
Adenocarcinoma may present singly or in cell aggregates composed of a few cells to a large papillary fragment
These may be neatly circumscribed, non-vacuolated spheroids, some termed ‘proliferation spheres’
These proliferation spheres may be hollow or solid
In smears the hollow appearance results in an empty sphere
Mesothelioma cells may also form these spheres however with close investigation mesothelial differentiation can be determined
Metastatic Adenocarcinoma of the Breast
Metastatic breast carcinoma are mostly found in pleural effusions, occasionally in peritoneal and pericardial.
Patient will have a clinical history of treated breast carcinoma
An effusion 2º to the primary may not occur for decades after initial treatment of the 1º lesion
Due to the high incidence of breast carcinoma, the frequency with which it metastasises to serous membranes is important
Cytology of Metastatic Breast Carcinoma
Usually abundantly cellular
Aggregates may appear as rounded spheres
On CB preparation these spheres may be solid or hollow
The hollow appearance may suggest a cribriform growth pattern
Cytology of Metastatic Breast Carcinoma - Lobular Carcinoma
Typically present as numerous small, isolated malignant cells
These can be mistaken for macrophages or mesothelial cells
However, they appear monotonous throughout the smear
Uniform in appearance
Individual cells show irregular nuclear shape
Prominent nucleoli
These cells have a tendency to form small palisaded strips
Single cells may contain a large vacuole with a mucin target
IHC - Breast vs Other Adeno Carcinomas
Breast vs other - GCDFP-15 positivity indicates breast - Gata3 demonstrates high specificity for met breast ca ~90% - mammaglobin - expressed in 48%-72% of breast ca Breast vs Lung - TTF-1 positivity favours lung Breast vs ovarian serous - WT-1 positivity indicates ovarian, negativity favours breast Breast vs ovarian mucinous - CK20 positivity indicates ovarian - CA125 negativity favours breast Breast vs stomach - ER positivity favours breast - CK20 positivity favours stomach
Metastatic Adenocarcinoma of Lung
Approximately 40% of pleural fluid containing cancer cells are derived from primary carcinoma of lung
Cytology
- large, obviously malignant cells are present occurring singly or in papillary aggregates
- aggregates show glandular differentiation
- acinar arrangements
- eccentric, irregular nuclei
- prominent nucleoli
- abundant delicate vacuolated cytoplasm
- population of mesothelial cells in background
IHC for Metastatic Lung Ca
TTF-1: Positivity in 75% of cases (BAC is often negative for TTF-1) AE1/AE3: Positive CAM5.2 Positive CK7 usually positive CK20 usually negative EMA positive CEA positive Thyroglobulin negative
