Mucinous (Colloid) Adenocarcinoma of the Lung

Mucinous (colloid) adenocarcinoma (MC) of the lung is an unusual variant of pulmonary adenocarcinoma.

Discrimination between these tumours, mucinous cystadenomas, mucinous bronchioloalveolar cell carcinomas, and metastatic lesions with mucinous features may prove challenging, especially on small biopsy specimens.

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Mucinous (colloid) adenocarcinoma is suspected when a gelatinous substance like strawberry jelly is observed intraoperatively in the lung.

Grossly, the tumours are usually poorly circumscribed, soft, tan-to-gray mucoid lesions. Image Link

MC of the lung represents an entity with two distinct clinicopathologic and immunophenotypic variants:

1) the goblet cell-type, presenting a more indolent clinical behavior and frequently co-expressing markers of intestinal and pulmonary differentiation; and

2) the more aggressive signet-ring cell-type, which retains only markers of pulmonary origin.

Because it shares similar histologic features with mucinous adenocarcinomas of the gastrointestinal tract, ovary, and breast. Pulmonary MCC may require immunohistochemical analysis to confirm the primary site of the tumour.

- Patients with goblet cell - type MCC are more common and are frequently immunoreactive for intestinal-type markers such as CDX2, cytokeratin 20 (CK20), and MUC-2.

Additionally, the latter tumours appear to have a better prognosis.

- The less frequent signet ring cell - type MCC is immunoreactive for markers of pulmonary origin, such as TTF-1 and CK7, and nonreactive for intestinal-type markers such as CDX2, MUC2, and CK20.

In contrast to the goblet cell - type MCC , signet ring - type tumours are associated with a poorer prognosis.

In addition, one needs to distinguish mucinous cystadenomas and mucinous bronchioloalveolar cell carcinoma (BAC) from MCC.

Mucinous cystadenoma is a benign neoplasm that is generally much smaller, has a fibrous capsule, and lacks the cytologic atypia seen in carcinomas.

Although mucinous BAC, the most common pulmonary mucin-rich neoplasm, and pulmonary mucinous carcinoma share similar morphologic features, clinical, radiologic, and microscopic characteristics are distinctly different (Eg : BAC frequently disseminates in a lepidic-like growth pattern through airspaces, giving a multicentric appearance).

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Histological classification of lung and pleural tumors. In: Travis WD, ed. WHO International Histological Classification of Tumors: Histological Typing of Lung and Pleural Tumors. 3rd ed. Berlin, Germany: Elsevier Publishing Co; 1999:21–66.

Mucinous (colloid) adenocarcinoma of the lung.Arch Pathol Lab Med. 2005 Jan;129(1):121-2.

Mucinous (so-called colloid) carcinoma of the lung.Am J Surg Pathol. 2004 Oct;28(10):1397; author reply 1397.

Comparison of the immunophenotypes of signet-ring cell carcinoma, solid adenocarcinoma with mucin production, and mucinous bronchioloalveolar carcinoma of the lung characterized by the presence of cytoplasmic mucin.J Pathol. 2006 May;209(1):78-87.

The latest World Health Organization (WHO) classification divides adenocarcinoma mainly into adenocarcinoma mixed subtypes, acinar adenocarcinoma, papillary adenocarcinoma, bronchioloalveolar carcinoma, and solid adenocarcinoma with mucin production, and it mentions several variants, including fetal adenocarcinoma, mucinous ("colloid") adenocarcinoma, mucinous cystadenocarcinoma, signet-ring adenocarcinoma, and clear cell adenocarcinoma. In general, the mucin-producing adenocarcinoma of the lung comprises signet-ring cell carcinoma (SRCC), solid adenocarcinoma with mucin production (SA), and mucinous bronchioloalveolar carcinoma (m-BAC), mucinous ("colloid") adenocarcinomas and/or mucinous cystadenocarcinoma, and mucoepidermoid carcinoma. As SRCC, SA, and m-BAC exhibit distinct clinical features, it is important to identify differences in their immunohistochemical characteristics to better understand their histogenesis. In this study we analysed SRCC, SA, m-BAC, normal lung, and foregut-related secretory tissue for immunohistochemical differences using tissue microarrays. SRCC and SA showed high expression of MUC1 (97.4% and 100%, respectively), cytokeratin (CK) 7 (both 100%), and thyroid transcription factor-1 (TTF-1) (81.1% and 100%, respectively). They also showed low expression of MUC5AC (25.5% and 21.1%, respectively) and MUC6 (18.3% and 10.5%, respectively), whereas m-BAC showed high expression of MUC5AC (97.5%), MUC6 (75.0%), and CK7 (94.7%), but low expression of MUC1 (57.5%), and TTF-1 (27.5%). Hierarchical clustering showed that the immunophenotypes of SRCC and SA belong to the same category as alveolar lining cells, whereas m-BAC clustered onto another branch with gastric foveolar cells and bronchial goblet cells. These immunohistochemical findings support the results of our previous clinicopathological analysis of SRCC of the lung showing that SRCC occurs anatomically in the peripheral portion of the lung rather than in the bronchial gland-bearing portion.

Mucinous (colloid) adenocarcinoma.Jpn J Thorac Cardiovasc Surg. 2005 Jun;53(6):305-8.

We describe a case of primary mucinous (colloid) adenocarcinoma of the lung. The patient was a 61-year-old male with a peripheral mass of the left lung. Retrospectively, the mass, which showed slow growth later, could be seen in a chest X-ray 3 years before surgery. The tumor was filled with a gelatinous substance resembling strawberry jelly, macroscopically. Microscopically, it was mucin with a small amount of malignant cells (adenocarcinoma). Diagnosis was mucinous (colloid) adenocarcinoma, which is a very rare intrapulmonary neoplasm. Mucinous (colloid) adenocarcinoma is suspected when a gelatinous substance like strawberry jelly is observed intraoperatively in the lung.

The spectrum of pulmonary mucinous cystic neoplasia : a clinicopathologic and immunohistochemical study of ten cases and review of literature.Am J Clin Pathol. 2005 Jul;124(1):62-70.

We describe 10 new cases and review 66 previously reported cases of primary pulmonary mucinous cystic neoplasia (PMCN). The 3 men and 7 women were 44 to 73 years old (mean, 60.0 years) at diagnosis. Lesions were found by chest radiograph (featuring a solitary, lobulated nodule with soft tissue density that enlarged slowly), or patients had major bronchial occlusion by mucus or hemoptysis. Tumors were well-circumscribed, lobulated soft masses with a central cavity filled with gray to greenish translucent mucus and were 1.5 to 5.5 cm in greatest dimension (mean, 3.3 cm). Microscopically, confluent lakes of mucin characterized all cases. Tumor epithelium ranged from bland to focal cytologic atypia to frankly malignant. The adjacent lung parenchyma was stretched, compressed, or showed an inflammatory reaction to dissected mucin. After 1- to 10-year follow-up (mean, 3.7 years), 3 patients died of metastasis and 1 of amitriptyline toxic effects; 6 were alive without tumor. Combined analysis of our cases and previously reported cases suggests a histologic spectrum from benign cystadenoma to mucinous cystic tumor with atypia to well-differentiated mucinous cystadenocarcinoma. The histomorphologic criteria derived from this analysis can help distinguish PMCN from other types of primary or metastatic mucinous tumors and predict outcome.

Primary mucinous (so-called colloid) carcinomas of the lung: a clinicopathologic and immunohistochemical study with special reference to CDX-2 homeobox gene and MUC2 expression. Am J Surg Pathol 2004;28:442–452.

Herein we describe the clinicopathologic and immunohistochemical features of 13 primary mucinous (colloid) carcinomas (MCs) of the lung, an uncommon and controversial tumor. The patients, 7 males and 6 females, ranged in age from 50 to 79 years (mean, 64.5 years). All the tumors presented as a peripheral solitary nodule with gelatinous cut-surface and well circumscribed but lacking a complete fibrous wall. The size ranged from 1 to 5.5 cm. Microscopically, they consisted of neoplastic elements floating in large mucin pools and focally lining the alveolar spaces. Eleven cases were predominantly composed of tall, columnar goblet cells (goblet cell-type MC), while 2 consisted of signet-ring tumor cells (signet-ring cell-type MC). Five tumors were incidentally discovered by chest radiographs, while the others were symptomatic. All patients underwent complete surgical resection (six lobectomies and seven wedge resections). Postoperative chemotherapy was performed in 3 cases. Overall, the median follow-up was 26 months (mean 33 months; range 9-95 months). All patients with goblet cell-type MC were alive and well, while the 2 patients with signet-ring cell-type MC died of disease. Immunohistochemically, all the 11 goblet cell-type MCs were strongly stained with CDX-2 and MUC2, 8 reacted with TTF-1, 6 with cytokeratin 20 (CK20), 9 with cytokeratin 7 (CK7), and 2 with MUC-5AC. Conversely, the two signet-ring cell-type MCs were stained with TTF-1, CK7, and MUC5AC but were negative for CDX-2, MUC2, and CK20. Surfactant apoprotein-A (SP-A) was positive in four goblet cell-type and one signet-ring cell-type MC. When compared with 10 mucinous bronchioloalveolar carcinomas (m-BAC), the latter reacted with CK7, CK20, MUC5AC, TTF-1, SP-A, CDX-2, and MUC2 in 100%, 90%, 100%, 30%, 10%, 0%, and 0% of the cases, respectively. In summary, MC of the lung represents an entity with two distinct clinicopathologic and immunophenotypic variants: 1) the goblet cell-type, presenting a more indolent clinical behavior and frequently co-expressing markers of intestinal and pulmonary differentiation; and 2) the more aggressive signet-ring cell-type, which retains only markers of pulmonary origin. On morphologic and immunohistochemical grounds, MCs are easily distinguishable from m-BAC. Since goblet cell-type MC strongly stains with CDX2, MUC2, and CK20, differential diagnosis with metastatic colorectal carcinoma is very challenging and requires appropriate clinical correlation.

Mucinous carcinoma (colloid carcinoma) of the lung diagnosed by fine needle aspiration cytology: a case report.Malays J Pathol. 2003 Jun;25(1):63-8.

Mucinous carcinoma of the lung, also known as colloid carcinoma, is an uncommon tumour that is rarely encountered in fine needle aspiration (FNA) cytological practice. A 64-year-old Chinese male presenting with blood stained sputum and hoarseness of voice was discovered to have a 3 cm sized mass in the left lung. Neither bronchial washings nor transthoracic FNA yielded positive results at this stage. Six months later the patient returned to the hospital with a larger tumour and mediastinal lymphadenopathy. Transbronchial lymph node FNA, reported as negative for malignancy showed normal, hyperplastic and mildly atypical bronchial epithelial cells as well as a few single cells and extracellular mucin. Transthoracic FNA of the lung lesion performed under computed tomographic guidance showed characteristic cytological features of this tumour, establishing the diagnosis.

Pulmonary mucinous cystadenocarcinoma: report of a case and review of the literature.Ann Thorac Surg. 2003 Nov;76(5):1738-40.

A case of primary mucinous cystadenocarcinoma of the lung is presented. The patient was a 42-year-old woman with a 5-cm left lung mass. Left lower lobectomy was performed and analysis of a frozen section revealed mucinous cystadenocarcinoma. The tumor was a fibrous, walled cyst containing abundant mucinous material. Sparse groups of malignant cells were microscopically observed in pools of mucin; thus, the tumor resembled mucinous cystadenocarcinoma that occurs in the ovary, appendix, or pancreas. The tumor we found is a very rare intrapulmonary neoplasm that is differentiated from a metastatic lesion and mucinous bronchoalveolar carcinoma by its very different clinical course and prognosis.

Fine needle aspiration cytology of mucinous cystadenocarcinoma of the lung: report of a case with radiographic and histologic correlation.Acta Cytol. 2001 Sep-Oct;45(5):779-83.

BACKGROUND: Mucinous cystadenocarcinoma of the lung is an uncommon tumor. Because it contains relatively few neoplastic cells relative to the amount of mucin produced, diagnosis of this entity, particularly on small specimens, is exceedingly difficult. CASE: The diagnosis of adenocarcinoma was made on transthoracic fine needle aspiration from a patient with a right upper lobe lung mass. Abundant mucoid material suggested a mucin-producing neoplasm. Histopathology revealed a mucinous cystadenocarcinoma with focal mucinous bronchoalveolar carcinoma. CONCLUSION: The presence of copious extracellular mucin in fine needle aspirates from the lung otherwise diagnostic of adenocarcinoma should raise the possibility of a mucinous tumor. In particular, the diagnosis of mucinous cystadenocarcinoma may be suggested in cases that have a cystic appearance on imaging studies.

Mucinous (so-called colloid) carcinoma of the lung. Mod Pathol 1992; 5:634–638.

We present 24 cases of primary mucinous (so-called colloid) carcinomas of the lung. The patients were between 33 and 81 yr old (median: 57 yr), including 15 men and nine women. The lesions were discovered incidentally on chest X-ray, where they presented in diverse forms. No predilection for a particular lobe or pulmonary segment was observed. The tumors varied from 0.5 to 10 cm in greatest diameter. Grossly, the tumors were poorly circumscribed, soft, tan-to-gray mucoid lesions. Microscopically, they showed intra-alveolar pools of mucin containing small clusters of atypical cells floating in the mucin, and foci of neoplastic columnar epithelium lining scattered alveoli. Seven cases showed areas of solid, well-differentiated malignant glands adjacent to pools of mucin. In two cases, lymph node metastases were found at surgery. Eleven (57%) of 19 patients were alive over a follow-up period ranging from 2 to 192 mo; one of them had metastases to bone and another had intrapulmonary recurrence. Eight patients died with/of their tumors, two of them with known metastases to bone and/or brain, and one with recurrence after 2 yr of initial diagnosis. No follow-up was obtained in five patients. Although the extent of clinical evaluation varied, no other primary neoplasms (i.e., breast, gastrointestinal tract, or other organs where primary mucinous carcinomas are known to occur) were observed. These tumors probably represent a variant of bronchioloalveolar carcinoma and share the prognosis of that neoplasm. However, because of their often bland cytologic features and paucity of malignant cells, they may be difficult to diagnose as neoplasms.

June 2007