Large Cell Carcinoma & Giant Cell Carcinoma UNDIFFERENTIATED LARGE CELL CARCINOMA As its name implies, undifferentiated large cell carcinoma shows no evidence of squamous or glandular maturation. Thus these tumors are often diagnosed by default, when all other possibilities have been excluded. Large cell carcinoma represents 10-20% of bronchogenic tumors. These tumors lack any diagnosic features to suggest their diagnosis prior to biopsy. They tend to grow rapidly, metastasize early, and are strongly associated with smoking. Because of the small samples obtained in biopsies, larger resection specimens often yield more information and change the diagnosis to adenocarcinoma or squamous cell carcinoma. Glandular differentiation is found more common than squamous in tumors that have previously been diagnosed as large cell undifferentiated on small biopsies. This correlates with the gross observation that these tumors tend to be present peripherally, like adenocarcinomas. Gross Appearance Large cell tumors are usually large, bulky, well-circumscribed, pink-grey masses with extensive hemorrhage and necrosis. Although they commonly have central necrosis, they rarely cavitate. They tend to present in the mid to peripheral lung zones. They may extend locally to involve the segmental or subsegmental bronchi. Microscopic Features Undifferentiated large cell carcinoma are defined by the WHO as "a malignant epithelial tumor with large nuclei, prominant nucleoli, abundant cytoplasm and usually well defined cell borders, without the characteristic features of squamous cell, small cell or adenocarcinomas." Their diagnosis is made when elements of squamous ar glandular differentiation cannot be proven. The cells are generally round to polygonal and present in groups without any higher architectural features. As a rule, the nuclei are large and round with prominant nucleoli. Due to the necrosis that frequently accompanies these tumors, there are zones of dropout within the middle of the specimens, which may suggest a glandular lumen. Sometimes there may be a variable population of the cells that have a clear cytoplasm, however, they stain negatively for mucin with either a mucicarmine or periodic acid-Schiff with diastase stain. For this reason, obtaining a mucin stain is imperative to make the diagnosis. It has been reported that in approximately half of the cases where undifferentiated large cell carcinoma is suspected, a mucin stain will be positive, thus designating the tumor as an adenocarcinoma. For a mucin stain to be considered truely positive, intracytoplasmic mucin must be identified. Extracellular mucin positivity is not significant. Immunohistochemical stains have shown undifferentiated large cell carcinomas to be a diverse group of tumors including poorly differentiated adenocarcinomas and squamous cell carcinomas. Based on cytokeratin expression, there are type major populations within this category. One group expresses simple epithelial cytokeratins, and is considered to be a poorly differentiated adenocarcinoma. While the other population, sugggested to be a poorly differentiated squamous cell carcinoma, expresses cytokeratins more commonly associated with squamous epithelia. GIANT CELL CARCINOMA Giant cell carcinoma is categorized by the WHO as a variant of large cell carcinoma. This subtype is particularly aggressive and carries a very poor prognosis. Gross Appearance These tumors generally present as a large peripheral mass with a focal necrotic component. They do not involve the large airways, unless by direct extension. Microscopic Features Giant cell carcinoma is recognized as a large cell carcinoma with a component of highly pleomorphic multinucleated cells. The nuclei are varied in size and shape. Generally, they are large and irregularly shaped with clumped chromatin and one or more nucleoli. However, the range of nuclear features extends to include multiple small nuclei within a cell. It is considered that at least 30-50% of these cells be present before making the diagnosis. These cells generally contain a large amount of finely vacuolated eosinophilic cytoplasm. Cell cohesion is frequently lost. There is often a necrotic component to these tumors, resulting in a neutrophilic or monocytic inflammatory cell infiltrate. Immunohistochemical stains can be useful in differentiating this tumor from a wide variety of other tumors that may be suggested by its histologic appearance. Negative staining for mucin differentiates it from an adenocarcinoma. Positive staining for cytokeratins is useful in eliminating sarcomas as a possibility. The loss of cell cohesion may suggest a lymphoma. However, unlike lymphomas, giant cell tumors are negative for leukocyte common antigen (CD45). These tumors are sometimes postive for humoan chorionic gonadotrophin (hCG) and may superficially resemble choriocarcinomas. Pathologic Types Adenocarcinoma R.B. is a 57 year old white female who
presents with a 4 year history of sharp burning pain in the right scapular area that
radiates to the right breast area. The alcohol-fixed, Papanicolaou-stained smears of the lung aspirate contain cohesive
groups of cytologically malignant cells with increased nuclear:cytoplasmic rations,
nuclear pleomorphism, and prominent nucleoli. The vague acinar arrangement of the cell
groups and absence of any squamous
Histologically, the tumors are well-differentiated, with a peglike cellular growth
along alveolar walls. L.M. is a 66 year old man currently being evaluated for clinical stage C prostate
cancer. A pre-operative chest x-ray revealed a suspicious lesion in the right lung, and
was referred for evaluation. He denies fevers, headaches, dysphagia, or chest discomfort,
however he does have dyspnea on exertion and occasional hemoptysis. He has a 25 pack year
smoking history, but he quit smoking 25 years ago. Images from the pleural fluid obtained by pleurocentesis. In the upper image, note the
large tumor cells within and adjacent to the cluster of cells. The lower image is a
close-up of the cells. Again, note their size, as well as the large nuclei which contain
prominant nucleoli. E.C. is a 65 year old woman referred to the clinic for the evaluation of a lung mass
found on a CT scan. The scan was obtained to look for metastatic spread of her breast
cancer before beginning chemotherapy. Three weeks prior to clinic she underwent a left
breast biopsy and modified radical mastectomy to remove a 5 x 6 cm breast mass identified
as infiltrating ductal breast carcinoma extending into the lymphatics. Surgically her
breast cancer was classified as a stage IIIA. Her only
Low power photomicrograph of the cyst wall demonstrates all of the benign tissue types normally found in bronchial structures. Note the single epithelial layer, the underlying smooth muscle cells, and the mature cartilage (in the image on the right). Mature cartilage is often present in the wall of a bronchial cyst.
K.V. is a 55 year-old female patient with increased fatigue, dyspnea on exertion, and a persistent dry cough. She denies fever, chills, or hemoptysis, and has no recent weight change. She smokes half of a pack of cigarettes per day and has a 60 pack year history.
PA chest X-ray reveals a large suprahilar density. There is bilateral pleural thickening, with calcification.
This is a low power photomicrograph of the tumor showing the relatively small,
cytologically bland tumor cells forming a nest under the bronchial epithelium. Y.Z. is a 55 year old, male college professor who was referred from his local physician
for evaluation of persistently elevated serum thyroglobulin.
Chest CT shows a nodule behind a rib on the left.
Low and high power photomicrographs of the chondrosarcoma. The lesion shows the
abundant blue-grey chondroid matrix typical of cartilaginous growths. The features which
distinguish this lesion as a malignant cartilaginous neoplasm are its marked cellularity
and the pleomorphism of the individual chondrocytes.
Chest CT confirms the presence of a less than 1 cm nodule, as well as multiple nodules over the right upper lobe.
A photomicrograph of a granuloma, the upper image is low power view. In the center is
the necrotic core, which is surrounded by epitheloid histiocytes and a chronic
inflammatory reaction. The lower field is a close-up of the three classical layers of a
granuloma: the central zone of necrosis, the middle zone of epithelioid histiocyes, and
the outer cuff of small lymphocytes. Note that some of the
R.C. is a 53 year old man recently seen in the emergency room for the evaluation of
hemoptysis. A chest x-ray showed an anterior mediastinal mass, which was confirmed on CT.
He now presents a week later in clinic for follow-up. The hemoptysis has continued,
however the sputum no longer contains large clots but does not contain streaks of blood.
He denies any fever, chills, or recent
Chest CT confirms the presence of the anterior mediastinal mass.
The tumor is removed from the chest cavity. Upon examination, a portion of the resected right upper lobe (RUL), pericardium (P), and tumor (T) are seen.
A CT demonstrating the tumor compressing the pulmonary artery and collapsing the lung against the chest wall.
A.O. is a 64 year old woman who was referred to the clinic after an abnormal density in the left suprahilar area was found on a preoperative chest x-ray prior to the resection of her bladder tumor. She denies any dyspnea, orthopnea, edema, cough, hemoptysis, fevers, chills, night sweats, or weight loss.
The patient's PA chest x-ray demonstrating the mass.
Pictures taken during surgery. Above, the forceps are pulling the pericardial cyst.
The upper image is a low power photomicrograph of the simple cyst. At this power note the vascularized fibrous connective tissue of the wall. The lower picture is a view of a similiar area at high power. The cyst is lined by a simple epithelium ranging from cuboidal to flat. This type of epithelial lining is characteristic of mesothelium. Note the absence of any evidence of malignancy, such as an infiltrating population of cells or significant cytologic atypia.
J.B. is a 35 year old male who came to the clinic for a second opinion of a left upper
lobe infiltrate. He reported that he had been healthy all of his life until 6 months
ago, when he began to experience symptoms of cough and pleuritic chest pain with dyspnea
at minimal exertion. Initially he was treated for pneumonia, however, he remained
symptomatic following treatment with various antibiotics. A chest CT reveals that there is no contrast filling of the left pulmonary artery. The mass can be seen within the pulmonary artery.
A normal day 5 post-operative chest X-ray reveals that he still has an air fluid level in the upper fifth of his left chest cavity. His right chest is clear.
images (x-ray and CT) from a patient with small cell lung carcinoma A head CT revealed a single lesion of the right parietal lobe.
Selected images from the transthoracic fine needle aspirate biopsy. These cells were stained using the standard Papanicolaou technique. Atypical cells such as these, with their classical "tadpole" morphology, are diagnostic of squamous cell carcinoma. All of these cells exhibit increased nuclear size, nuclear irregularity, and nuclear hyperchromasia. The cytoplasm is very uniform and lacks vacuolization. The glassy orange appearance of the cytoplasm is indicative of keratin formation, a feature of squamous differentiation.
A mediastinal windows CT scan shows the anterior mediastinal mass. It appears to have a soft tissue quality with sharp boarders and without calcification.
A high power photomicrograph of the proliferative epithelium lining the wall of the thymic cyst. Multiloculated cysts have a multilayered proliferative epithelial lining while unilocular cysts have a simple squamous epithelial lining.
A PA chest x-ray showing a cavitary lesion in the right lower lobe. Note the air-fluid
level within the lesion. Several fields from the fine needle aspiration biopsy. Each field contains malignant
cells which are characterized by their clumping, large size, increased
nuclear-to-cytoplasmic ratio, and irregularly shaped nuclei with multiple nucleoli.
Because of their large size, nuclear features and the lack of evidense of squamous or
glandular differentiation, these cells are classified as nonsmall cell lung cancer. In
contrast, small cell lung cancer cells are smaller, contain little cytoplasm, and the
nuclei contain very dense chromatin. |
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