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January, 2018
Case of the Month

Clinical History: A 75 year old female with a history of a previously resected right upper lobe pulmonary adenocarcinoma presented with two nodules in the left upper lobe 14 years later. The patient underwent a left upper lobe wedge resection encompassing both radiographic nodules.  Grossly, distinct 10.0 mm and 4.0 mm nodules were identified.  The larger nodule was a classical non-mucinous acinar predominant adenocarcinoma; however, the smaller nodule had a different appearance, as illustrated in Figures 1-6.

Quiz:

Q1. Which of the following is true about the expected behavior of this lesion?

  1. Aggressive behavior with early metastases
  2. Locally aggressive spread, ultimately producing a “pneumonic” type consolidation of the lung
  3. Indolent behavior, putatively benign
  4. Highly likely to recur after resection

Q2. Which is the following is true about this lesion?

  1. It is a variant of mucinous adenocarcinoma
  2. It is a type of peribronchiolar metaplasia
  3. It is a variant of mucoepidermoid carcinoma
  4. It is postulated to be part of a spectrum of bronchial adenomas

Q3. Which is the following is true about this lesion?

  1. It does not have known genetic abnormalities
  2. It is characterized by an EWSR1-CREB1 fusion
  3. It has most frequently shown mutations in BRAF, but mutations in EGFR, KRAS and other driver genes have been reported.
  4. It classically has a SMARCB1 or SMARCA4 deficiency

Answers to Quiz

Q1. C
Q2. D
Q3. C

Diagnosis

Ciliated muconodular papillary tumor

Discussion

Ciliated muconodular papillary tumor (CMPT) is a rare neoplasm of the lung, typically found as a peripheral lung nodule. CMPT was initially described by Ishikawa in 2002. There are currently around 40 cases reported in the literature, with the number increasing in recent years, likely owing to improved recognition of the tumor. Thus far, the majority of these have been reported in East Asian patients with a slight female predominance. The tumors classically present as a peripheral nodule that may be well-demarcated, irregular in shape, or have a ground glass appearance, thus mimicking a lung carcinoma. Histologically, CMPT consists of tripartite cellular components of mucinous and ciliated cells overlying a layer of basal cells. The basal cells express markers such as p40, p63 and CK5/6 while the mucinous and ciliated cells are positive for CK7, variably positive for TTF-1 and negative for the basal cell markers. TTF-1 staining has also been reported in the basal cells. CK20 and CDX-2 are negative. While CMPT classically shows papillary architecture, it may also show varying degrees of glandular, lepidic and even micropapillary growth. Intra-alveolar mucin is typically present around the periphery of the lesion. The double layer of cells and presence of cilia are of particular importance in discriminating CMPT from mucinous adenocarcinoma. A variety of mutations have been reported in CMPT, most commonly BRAF G606R or BRAFV600E; however, EGFR, AKT1, KRAS G12D, KRAS G12V, ALK gene rearrangements and p14 INK4a overexpression have also been reported. The presented case harbored a KRAS G12C mutation. CMPT has an indolent clinical course and has been more recently proposed as occurring as part of a spectrum of bronchial adenomas.

Take home message for trainees:
CMPT is a rare but increasingly recognized neoplasm of the lung which may be easily mistaken for mucinous adenocarcinoma.  The bi-layered tumor morphology consisting of ciliated and mucinous cells overlying a uniform row of basal cells is a unique feature of CMPT which should aid in identification.


References

Chang JC, Montecalvo J, Borsu L, et al. Bronchiolar adenoma: Expansion of the concept of ciliated muconodular papillary tumors with proposal for revised terminology based on morphologic, immunophenotypic, and genomic analysis of 25 Cases. Am J Surg Pathol 2018; 42: 1010-1026

Ishikawa, Y., Ciliated muconodular papillary tumor of the peripheral lung: benign or malignant. Pathol Clin Med (Byouri-to-Rinsho) 2002; 20: 964-965.

Kamata, T.; Yoshida, A.; Kosuge, T, et al. Ciliated muconodular papillary tumors of the lung: a clinicopathologic analysis of 10 cases. Am J Surg Path 2015; 39: 753-60.

Kamata, T.; Sunami, K.; Yoshida, A., et al. Frequent BRAF or EGFR Mutations in ciliated muconodular papillary tumors of the lung. J Thor Onc 2016; 11: 261-5.

Kon, T.; Baba, Y.; Fukai, I., et al. Ciliated muconodular papillary tumor of the lung: A report of five cases. Pathol Intl 2016; 66: 633-639.


Contributors

Shahram Saberi, MD and Mary Beth Beasley, MD
Department of Pathology
Icahn School of Medicine at Mount Sinai
1 Gustave L. Levy Pl
New York, NY 10029
USA



2017 PPS Lifetime Achievement Award
Professor Thomas Colby
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