Difficult situations in lung nodules frozen sections analysis.
I have been working in lung pathology for more than 10 years. Frozen sections are a common request from lung surgeons. I have a fairly complete record of the procedures in which I have participated, more than 3000. Reviewing my experince I found four situations particularly difficult to resolve in the intraoperative consultation.
Usually we performed imprint or scrapped preparations cytology stained with Hematoxilyn-Eosin or Methylen Blue 1% solution. If these slides are not conclusive frozen sections of selected samples are prepared and stained with H&E.
I hope these examples could help others to prevent the mistakes I have commited.
1. Cavitated mass/nodule. TACAR unconclusive. Abscess vs Carcinoma with necrosis.
First scenario: Incisional biopsy. If fibrotic wall with islands of squamous epithelium and severe inflammation is observed, and no definite atypia of the epithelial component is present a diagnosis of abscess could be rendered.
That is not correct. This picture does not rule out carcinoma. Frequently, extensively necrosed epidermoid carcinomas are only represented by invasive nests of bland epithelium, that are only focally preserved. Thus, the incisional biopsy could not be representative of the malignant tumor. A negative incisional biopsy should prompt the request of aditional biopsies or the ressection of the whole lesion
Second scenario: Ressection of the whole lesion. A cavited mass filled with granular and purulent material. Wall irregularly thickened, with gelatinous areas. Many samples of the wall are obtained for frozen sections and they show fibrosis, inflammation and squamous epitehlium. Once again hyperplastic changes of the metaplastic epithelium could be inferred with pseudo-invasive patterns. The intense necroinflammation is in concert with an abscess. Thus, diagnosis of lung abscess is rendered.
That is not correct. Extensively necrotic Epidermoid carcinoma coul be present in just few focus of the lesion, and sampling could miss them. Sometimes the embedding of the lesion in toto is the only way to confirm benignancy or malignancy.
2. Similar case.
The incisional biopsy shows fibrosis, nests and islands of solid squamous epithelium with bland cytology but some nuclear figures alarming, sourrounded by mixed inflamation. Mitosis are present, and invasion is considered. A diagnosis of Epidermoid Carcinoma is rendered.
That is not correct. Long standing lung abscess develops squamous metaplasia that could be florid and pseudo-invasive. In episodes of acute inlflammation mitosis and atypia are common in concert with epithelial regeneration. Once again a request for aditional biopsies is mandatory or the whole ressection. Only the wide sampling could be unequivocal in defining malignancy in these cases.
3. Lung nodule. Cancer is suspected by TACAR.
Atypical ressection is performed. The pathologist has the entire lesion to analize. A solid, expansive mass, tan coloured is observed. Grossly, carcinoma seems a good diagnosis. Imprints and frozen sections show nests and nodules of large cells with abundant eosinophilic cytoplasm, nuclei are mildly enlarged, with frequent nucleoli. Many cells exhibit high nucleo/cytoplasmic ratio. Necrosis is present. A diagnosis of Epidermoid carcinoma is rendered.
That is not correct. Granulomatous reactions (tuberculosis in this case) could present as solid masses of epithelioid cells, lightly atypical, associated with necrosis. High nucleo/cytoplasmic ratio is frequently observed in the morphologic spectrum of active macrophages, specially when they are monocytes recently recruited. Clues to diagnosis are the abscense of definite atypia and keratinization in a lesion of bland cytology that would be well differentiated.
4. Similar case but now there are extensive areas of necrosis.
Grossly, such creamy material could be interpreted as keratin. Microscopy show the same aspect as the previous case, but giant cells are present and the creamy material was interpreted as caseum. A diagnosis of tuberculosis is rendered.
That is not correct. Epidermoid carcinoma is frequently associated with extensive keratinization, which in turn could be inflammed. Keratin ellicit giant cell reactions and granulomas when present in the connective tissue. Clues for diagnosis are the presence of groups of epidermoid cells, even with unremarkable atypia, and recognizing masses of keratin as what it is, not necrosis.
In conclusion, for cavited mass lesions of the lung, only the diagnosis of malignancy is reliable in frozen sections. The possibility of a false negative is high, and depends on sampling errors, misinterpretation,etc, and the probability of error is higher in biopsy material.
In the case of solid lesions with epithelioid cells and necrosis, the possibility of granulomatous infection must be always taken in consideration, but if epidermoide clusters with or without definite atypia are present, and keratin is identified merged with necrosis, carcinoma should bediagnosed. We observed one case of coexistence of tuberculosis and epidermoid carcinoma in the same lesion, an absolutely exceptional situation that merits just for anecdote.
In many cases cytology slides let the observer to make diagnosis, specially if a malignant lesion is present. Negative cytology slides sholud be complemented with frozen sections to rule out malignancy. If the whole slides are negative, diagnosis of benignancy should be made carefully, and limitations of the technich must be comunicated to the surgeon. Grossly malignant lesions should be better treated as malignant if pulmonary function of the patient tolerates wide ressection. Imagenology and clinical impression are rarely wrong in appropiate hands. However, never lost from your focus that first of all you have to think in the patient.
Frozen sections of lung nodules is a widely performed procedure intended to aid the surgeon in taking therapeutic decisions in situ. A benign lesion could be cured with limited lung ressection but on the contrary, malignant lesions need oncologic surgery. Pathologic diagnosis are of prime importance in such context. A surgical pathologist should ideally be specialized in thoracic pathology or, at least, experienced in the field. Difficult situations are uncommon, but when one happens the actuant pathologist must be prepared to give the most accurate possible diagnosis. This paper highlights four of that difficult situations, extracted from our large serie of frozen sections in lung surgery.