Clinical History

A 47-year-old woman, former smoker, was found to have an incidental lung nodule during the workup of an appendiceal adenocarcinoma ex-goblet cell carcinoid. The chest CT showed a round, well-circumscribed solid nodule in the posterior left upper lobe abutting the major fissure, measuring 2.0 cm (Figure 1).  A trans-thoracic core needle biopsy was performed (Figures 2-6; Fig 3: pancytokeratin, Fig 4: epithelial membrane antigen, Fig 5: TTF-1, Fig 6: napsin A).  

Click thumbnails to see larger images

Figure 1 Figure 1   Figure 2 Figure 2   Figure 3 Figure 3   Figure 4 Figure 4   Figure 5 Figure 5   Figure 6 Figure 6

 

Quiz

Q1. This tumor is currently thought to be derived from what type of primitive cell?

  1. Histiocytes
  2. Blood vessels
  3. Neuroendocrine cells
  4. Primitive pneumocytes
  5. Mesothelial cells

Q2. What pattern is not typically associated with this tumor?

  1. Sclerotic
  2. Papillary
  3. Rosettes
  4. Solid
  5. Hemorrhagic

Q3. The two cell types that comprise this entity show overlapping but distinct immunohistochemical profiles. Which immunostains tend to be diffusely positive in both cell types?

  1. CAM5.2
  2. EMA and TTF-1
  3. Pan-cytokeratin
  4. Napsin A and CK7
  5. SMA and Chromogranin

Answers to Quiz

Answers to Quiz

Q1. D
Q2. C
Q3. B

Diagnosis and Discussion

Diagnosis and Discussion

Diagnosis

Sclerosing pneumocytoma

Discussion

Sclerosing pneumocytoma is a benign tumor classically presenting as an incidentally discovered solitary, peripheral, and round nodule in the lung. It occurs more often in women than men, and more often in East Asia than the West. It is slow growing and considered benign. Lymph node metastases are exceedingly rare and prognostically inconsequential. Sclerosing hemangioma was the original name given to this entity by Liebow and Hubbell in 1956 because it was thought to “consist largely of vessels obliterated by hyaline change, of extravasated blood, of cells engaged in the breakdown of the blood or in the storage of products of this breakdown, and of organization tissue.” However, current immunohistochemical data shows this tumor is not of vascular but of pneumocytic origin, and that there are two populations of cells:  surface cells and round cells (Figure 2). Lining the interstitium are the surface cells, resembling (or in fact representing) type II pneumocytes.  They are positive for markers of normal pneumocytes, including pan-cytokeratin, CAM5.2, EMA, CK7, TTF-1, and napsin A (Figures 3-6).  Within the stroma are round cells, which have well-defined borders, eosinophilic cytoplasm, bland nuclei, and no nucleoli. In fact, some authors have suggested that the lesional cells are only the round cells, whereas surface cells are entrapped benign pneumocytes. Round cells have an unusual immunoprofile in that they are negative for cytokeratin and napsin A but positive for EMA and TTF-1 (Figures 3-6).  While ER and PR are negative in the surface cells, interestingly, the round cells may show positivity in 7% and 61% of cases, respectively. Morphologic patterns that can be seen in sclerosing pneumocytoma include papillary, solid, sclerosing, and hemorrhagic (the latter two patterns originally described by Liebow and Hubbell). Other findings may include lamellar bodies, foamy macrophages, cholesterol clefts and fat. 

This case illustrates the difficulty of diagnosis with limited material resulting in a broad differential. The typical differential for sclerosing pneumocytoma with solid pattern includes carcinoid tumors.  For those with papillary pattern the primary differential is adenocarcinoma with papillary growth pattern. The differential for lesions with prominent sclerosing pattern and abundant stromal hyalinization includes other neoplasms with prominent myxohyaline stroma and bland cells, including epithelioid hemangioendothelioma and salivary-type neoplasms. Other vascular neoplasms may enter the differential diagnosis of lesions with a hemorrhagic pattern.  Sclerosing pneumocytomas are consistently negative for synaptophysin, chromogranin, and vascular markers such as ERG.  The distinctive immunoprofile of the round cells (TTF+/Napsin-/EMA+/CK-) helps distinguish these lesions from adenocarcinoma.

 

References:

  • Devouassoux-Shisheboran M, Hayashi T, Linnoila RI, et al. A clinicopathologic study of 100 cases of pulmonary sclerosing hemangioma with immunohistochemical studies: TTF-1 is expressed in both round and surface cells, suggesting an origin from primitive respiratory epithelium. Am J Surg Pathol 2000;24:906-16.
  • Kim KH, Sul HJ, Kang DY. Sclerosing hemangioma with lymph node metastasis. Yonsei Med J 2003;44:150-4. 
  • Liebow AA, Hubbell DS. Sclerosing hemangioma (histiocytoma, xanthoma) of the lung. Cancer 1956;9: 53-75.
  • Schmidt LA, Myers JL, McHugh JB. Napsin A is differentially expressed in sclerosing hemangiomas of the lung. Arch Pathol Lab Med 2012;136:1580-4.
  • Travis WD, Brambilla E, Nicholson AG, et al. The 2015 World Health Organization Classification of Lung Tumors: Impact of genetic, clinical and radiologic advances since the 2004 classification. J Thorac Oncol 2015;10:1243-60.

Contributors:

Joseph Montecalvo, M.D.
Thoracic Pathology research fellow
Department of Pathology
Memorial Sloan Kettering Cancer Center, New York, NY, USA

Natasha Rekhtman, M.D., Ph.D.
Thoracic Pathology Attending
Department of Pathology
Memorial Sloan Kettering Cancer Center, New York, NY, USA