A 72-year-old asymptomatic male with 25 pack-year smoking history underwent low dose computed tomography (CT) of chest for lung cancer screening. The CT imaging reported a subcarinal mass (5.5 × 3.9 × 2.0 cm). Endobronchial ultrasound confirmed a 2 cm subcarinal mass at Station 7. A transbronchial fine-needle aspiration (TB-FNA) of the lesion was performed [Figure 1] that aspirated thick milky and cloudy fluid.

Figure 1:: Direct smears of TB-FNA were hypocellular with predominance of cellular debris (a and b) with a few apical fragments of lining cells. These cell fragments demonstrated diagnostic features as seen in zoomed images (arrows) (a1 through a8 and b1 through b8). (a and a1 through a8: Papanicolaou stain; b and b1 through b8: Diff-Quik stain).

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QUESTION # 1

What is the most likely interpretation?

Metastatic carcinoma with cystic necrosis

Cystic hygroma (cavernous lymphangioma)

Esophageal duplication cyst

Ciliated lined cyst (bronchogenic cyst/ciliated foregut cyst)

Abscess

ANSWER TO QUESTION # 1

D. Ciliated lined cyst (bronchogenic cyst/ciliated foregut cyst)

The posterior mediastinal lesion was reported on CT scan as well demarcated smooth right subcarinal soft-tissue mass [Figure 2]. Aspirate from this lesion was thick and milky cloudy fluid with cytological features of ciliated lined cyst (bronchogenic cyst/ciliated foregut cyst) (Option d). It showed predominance of degenerated cellular debris admixed with scattered fragments of cells showing ciliary tufts [Figure 1]. These diagnostic cell fragments in this case were seen in direct smears but were few in number and required significant efforts to find them. Processing of the aspirate of such cystic lesion for cytopathological evaluation as liquid-based cytology (LBC) preparation (ThinPrep™ or SurePath™ or other similar method) or Cytospin™ would concentrate detached ciliary tufts (degenerated debris with ciliated cellular fragments of cell tops without nuclei similar to ciliocytophthoria) and occasional intact ciliated cells so that they could be detected with relative ease.[1] The cellular fragments with ciliary tufts could also be detected after diligent efforts in cell-block sections [Figure 3]. Cytomorphologically, these lesion cannot be distinguished from other ciliated lined cysts such as branchial cleft cyst and ciliated foregut cyst[1] without clinicopathological and imaging correlation.

Figure 2:: Unenhanced CT scan of thorax showing a smooth margined right subcarinal soft tissue mass (arrows) measuring 3.9 x 5.4 cm in the posterior mediastinum with no airspace consolidation, pleural effusion or pneumothorax.

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Figure 3:: Cell-block of TBFNA aspirate showing degenerated cellular debris with occasional cell fragments showing cilia (arrows). These cell fragments demonstrate diagnostic features as seen in zoomed images (a through f).

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Metastatic carcinoma (Option A) as metastasis of carcinoma of lung, breast, thyroid, and genitourinary tract is relatively common to the mediastinum. Although most of the metastatic carcinoma present as a solid lesion, they can have a cystic component with coagulative necrosis as tumor diathesis, some viable diagnostic malignant cells are expected be found in the sample. It can be challenging to sample such lesions adequately during rapid on-site evaluation due to a high percentage of non-diagnostic necrotic component. Sampling from the periphery of the lesions increases the diagnostic yield. If the cystic lesion does not resolve completely after the aspiration of cyst contents, the residual lesion should be sampled adequately.

Cystic hygroma (cavernous lymphangioma) (Option B) usually occurs in children. It may be located in the neck or axilla, often extending into mediastinum, and rarely present in the lymph node. Large mediastinal lesions may compress lungs, heart, and nerves, even though most lesions are asymptomatic. Microscopically large and irregular lymphovascular spaces are lined by flattened and bland endothelial cells with variable proportion of fibroblastic collagenous stroma. The aspirates are usually hypocellular with relatively non-specific findings including scant endothelial cells with bland morphology with a few scattered lymphocytes and histiocytes in the background of amorphous proteinaceous material.[2]

Esophageal duplication cysts (option C) are usually unilocular; however, they can be multiloculated with mucoid contents. Depending on the type of the cyst-lining, the aspirated cyst contents in addition to the debris show squamous, simple columnar, pseudostratified columnar, or mixed epithelial cells but are devoid of ciliated cells.

Abscess (Option E) shows purulent inflammation with predominance of neutrophils. Grocott-Gomori Methenamine Silver and Gram stain may show organisms such as fungi and bacteria. The organisms may also be seen with Diff-Quik stained direct smears and culture may grow causative organism(s).

QUESTION # 2

What are the diagnostic features of bronchogenic cyst?

Contains tissues derived from all germ cell layers

Contains cartilage and smooth muscle in the wall

Typically lined by respiratory, cuboidal, and/or squamous epithelium

Lined by stratified squamous or gastrointestinal epithelium.

None of the above.

Cystic teratoma is lined by variable mixtures of gastrointestinal, squamous, and respiratory epithelium. It typically contains tissues derived from multiple germ cell layers. Some cases may contain immature tissue with nuclear atypia.

Thyroglossal duct cysts may be lined by respiratory epithelium; however, their cyst walls contain thyroid follicles and lack smooth muscle and cartilage.

Esophageal duplication cysts are lined by stratified squamous or gastrointestinal epithelium. They are usually found to be attached to the esophageal wall and have two smooth muscle layers.

Dermoid cysts are lined by stratified squamous epithelium, contain hair, and other skin appendages with keratinaceous or sebaceous material.

Abscess may mimic bronchogenic cyst. However, an abscess neither will have a true lining nor cartilage and smooth muscle in their wall. They, however, may contain foci of squamous metaplasia. The aspirates predominantly show suppurative material as numerous acute inflammatory cells with variable degenerative changes.

Branchial cleft cysts resemble bronchogenic cyst with ciliated lining; however, they may show squamous metaplasia and lymphoid aggregates with reactive germinal centers. They may also be filled with keratinaceous debris. In contrast to this, the bronchogenic cyst wall shows smooth muscle with variable proportion of seromucinous glands and hyaline cartilage (Option B).

QUESTION # 3

Which of the following malignancies are reported in bronchogenic cyst?

Squamous cell carcinoma

Adenocarcinoma

Large cell carcinoma

Mucoepidermoid carcinoma

All of the above

Bronchogenic cysts are non-neoplastic hamartoma. However, similar to other anatomical tissues, rarely malignancy has been reported in bronchogenic cyst. The risk of malignancy in bronchogenic cyst is reportedly 0.7%.[3] So far, the reported cases include large cell carcinoma,[4] bronchoalveolar carcinoma, adenocarcinoma,[5] schwannoma.[6] mucoepidermoid carcinoma,[7] and squamous cell carcinoma.[8]

Pathophysiology of carcinogenesis in a bronchogenic cyst is not clear. One of the possibility is that the unstable epithelial cells in the cyst wall could have malignant potential leading to carcinoma. Whooley et al. reported squamous cell carcinoma of bronchogenic cyst in the paratracheal region.[8] A few researchers have reported diaphragmatic bronchogenic cyst with mucoepidermoid carcinoma.[7] Schwannomas are also reported in the wall of intrapulmonary bronchogenic cyst.[6]

QUESTION # 4

In the list mentioned below, which is the best diagnostic feature of a bronchogenic cyst?

Degenerated debris

Ciliated cell fragments

Intracystic proteinaceous material

Chronic inflammatory cells in a myxoid background

Numerous acute inflammatory cells

Being a cyst lined by ciliated epithelial lining, the aspirates from the cyst show debris of degenerated exfoliated lining cells with apical fragments of ciliated cells similar to ciliocytophthoria.

QUESTION # 5

Bronchogenic cyst can be seen in which of the following location(s)?

Midline superficial supra-sternal

Lateral to the thyroid

Around the hilum of the lung

Sub-carinal

All the above

Although the most common location of the bronchogenic cyst is superficial midline supra-sternal, it can also be found sub-carinal in the mediastinum, around the hilum of the lungs and lateral to the thyroid gland.

BRIEF REVIEW OF THE TOPIC

Bronchogenic cyst aka non-communicating bronchopulmonary foregut malformation is a relatively rare hamartomatous lesion with prevalence of approximately 1/42,000 admissions.[9] Although it is more commonly seen in pediatric population, it may be detected for the 1st time during adulthood without any sex predilection.

It usually originates as a late budding from the ventral side of embryonic lung or the tracheobronchial tree that occurs between the 26th and the 40th day of gestation. This abnormal bud then becomes a fluid-filled and blind-ending pouch termed bronchogenic cyst. Most of them are asymptomatic at birth and early life. Later in life, it may be symptomatic due to cyst enlargement leading to local compression and pressure on adjacent tissue/organ, occasionally secondary to infection or perforation.[10]

The site of bronchogenic cysts depends on the stage of development when the malformation occurs. The most common site is thorax, for example, mediastinum (early in development), and lung (later in development).[11] However, they have been reported in other sites such as neck, ileal mesentery, intradiafragmatic, intrapericardial, suprasellar, and laryngeal locations.[12] These lesions may remain asymptomatic until they are picked on imaging for screening or otherwise [Figure 2]. Neck lesions are reported to be more common in males than in females (3– 4:1).[13] Subcutaneous bronchogenic cysts are rare and are usually found in children as a small cystic lesion (<3 cm). Zheng et al. reported a 52-year-old woman presenting with a mass confirmed histologically as bronchogenic cyst in the left intergluteal cleft region.[14] Rarely bronchogenic cysts can be located in the pericardial space. Intrapericardial cysts consist of 27% of the bronchogenic cysts and often difficult to diagnose even with newer imaging modalities.[15] Intramural bronchogenic cysts of the esophagus are located in the upper mediastinum and are very rare.[16]

Bronchogenic cysts are lined by pseudostratified columnar or cuboidal ciliated (respiratory) epithelium. The cyst wall often contains smooth muscle fibers, elastic fibers, submucosal bronchial glands, and hyaline cartilage. The cyst wall helps to distinguish them from other ciliated lined cysts such as foregut cyst, duplication cyst, and branchial cleft cyst. The role of cytology is crucial to properly triage such patients. Endoscopic ultrasound-guided fine-needle aspiration (EUSFNA) in the current case was consistent with ciliated lined cystic lesion without malignant cells [Figure 1]. The definitive diagnosis of bronchogenic cysts depends on histological examination of the surgical specimen with hyaline cartilage, bronchial glands, and/or smooth muscle in the wall of the lesion.

Complete removal of the cyst, especially if symptomatic due to possibility of complications in the future, is the preferred recommendation. Approximately 50% of bronchogenic cysts present with pain.[17] Others may cause respiratory distress, cough, dyspnea, hemoptysis, dysphagia, nausea, vomiting, etc. Fever is a sign of infection and warrants a quick diagnosis with medical treatment and surgical removal as clinically indicated. Usually long-term prognosis with complete excision is assuring. However, incomplete excision may increase risk of recurrence.

The efficacy of EUS-FNA of cystic lesions partly depends on the site, size, and characteristics of the target tissue as well as on the expertise, training, and coordination between the procedure-performer and the cytology team.[18] Acquisition of diagnostic samples is approached in different ways depending on the site and type of the lesion. Cytological samples are ideal for cyst fluid analysis, IHC, and molecular testing as indicated. As observed in the present case, the direct smears are invaluable, both for immediate assessment and also for the final morphological interpretation. The needle rinses can be processed as LBC and cell-block. Cell-block increases the diagnostic accuracy of EUS-FNA in general.[1]

Bronchogenic cyst may be difficult to aspirate by TB-FNA, especially when the cyst content is thickly mucoid with debris. As observed in our case, intact ciliated cells could not be detected; however, there were many cell top fragments of the ciliated cells similar to ciliocytophthoria in Papanicolaou stained and Diff Quik stained direct smears [Figures 1 and 3]. These features would be relatively easily detectable in cytological preparations made with concentration methods such as LBC preparations including Surepath™,[1] ThinPrep™, and Cytospin™. Malignant cells or granuloma were absent in our case. Cell-block also showed similar findings; however, relatively few ciliated cell fragments showed significantly inferior morphology as compared to that seen in cytology preparations [Figure 3].

SUMMARY

A rare presentation or an uncommon lesion can be a clinical challenge. FNA cytology is minimally invasive modality for evaluation of space occupying lesions and for exclusion of malignancy. Although non-specific, the cytomorphological features in correlation with clinical and imaging details were consistent with bronchogenic cyst by detecting clues for respiratory type epithelium in the present case reported initially as mass lesion on imaging [Figure 2]. The detection of cell fragments with cilia similar to ciliocytophthoria [Figures 1 and 3] as diagnostic clue would be facilitated by proper processing with inclusion of concentration methodology such as LBC (SurePath™/ThinPrep™) or Cytospin™.[1]

Answers for Question 2 through 5:

2. B

3. E

4. B

5. E