Divya Bansal
Pulmonary sclerosing pneumocytoma (PSP) is a rare pulmonary tumor that behaves in
a benign fashion and has excellent prognosis.[1] The tumor was historically termed as sclerosing hemangioma by Liebow and Hubbell
in 1956.[2] The incidence peaks in sixth decade with a striking predilection for females (F:M = 5:1).[3]
[4] Although it presents as a well-circumscribed solid nodular mass, the radiological
features are nonspecific and can be misconstrued as malignant especially in large
tumors.[5] Frozen sections and trucut biopsy interpretation of such tumors may also be misleading.
A 26-year-old male, with a short-term smoking history, presented initially to other
institute with complaints of chest heaviness and mild pain for the last 6 weeks. Contrast-enhanced
computed tomography thorax revealed a well-defined solid pulmonary mass lesion in
right upper lobe measuring 4.3 × 3 × 2 cm. Few subcentimetric mediastinal lymph nodes
were noted ([Fig. 1]). Excision was done through right posterolateral thoracotomy, which was reported
as non-small cell carcinoma-adenocarcinoma (NSCC-ADC); pathological stage pT2N cannot
be assessed.
Fig. 1 Contrast-enhanced computed tomography thorax showed relatively well-defined nodular
lobulated mass lesion (
) in right upper lobe.
The patient then subsequently presented to our institute for further management with
radiological and histopathological review. Hematoxylin and eosin sections revealed
a well-circumscribed unencapsulated nodular tumor with a mixture of growth patterns:
papillary, solid, sclerotic, and hemorrhagic ([Fig. 2A]–[D]). The tumor had two cell types—cuboidal surface cells and oval-to-round stromal
cells ([Fig. 3A]–[B]). The complex papillae had cuboidal surface cells, while oval-to-round stromal cells
were in a streaming pattern. Few surface cells also showed clear vacuolated cytoplasm,
multinucleation, and intranuclear inclusions. Also evident were foci of mature fat
([Fig. 2C]), calcification and areas with hemosiderin pigment, foamy macrophages, and cholesterol
clefts. There was no evidence of high-grade cytological atypia or nuclear pleomorphism.
Mitosis was sparse.
Fig. 2 Hematoxylin and eosin stain shows mixture of growth patterns in sclerosing pneumocytoma.
(A) Papillary architecture that mimics true papillae. (B) Solid architecture with sheets of round stromal cells (
) with tubule (
) lined by surface cells. (C) Sclerotic papillae, fibrosis with hyalinized collagen admixed with a component of
mature fat (
). (D) Hemorrhagic pattern with blood filled spaces lined by cuboidal epithelium ().
Fig. 3 Sclerosing pneumocytoma. Images (A) and (B) show two tumor cell types: surface cuboidal cells () lining the papillae and round-to-oval stromal cells (). (C) Strong cytokeratin expression in surface cuboidal cells () while negative in round-to-oval stromal cells (). (D) Strong thyroid transcription factor 1 expression in both surface cuboidal cells () and round-to-oval stromal cells ().
On immunohistochemistry (IHC), the surface epithelial cells were diffusely positive
for pancytokeratin (CK) and thyroid transcription factor 1 (TTF1), whereas the underneath
stromal cells were positive for only TTF1 ([Fig. 3D]) and negative for cytokeratin (CK) ([Fig. 3C]). paired-box gene 8 (PAX8) was absent in both the components. Overall, clinical,
radiological, and histopathological features provided tangible evidence for the final
diagnosis of PSP. The patient is on 12 months of follow-up with no evidence of disease.
PSP is characteristically a small tumor, typically asymptomatic, detected incidentally
and shows a wide age range (11–80 years) distribution, commonly seen in middle-aged
Asian women.[1]
[3]
[4] The cell of origin for this tumor has remained enigmatic and has changed over time
and was previously conceived as vascular neoplasm.[2] Now, it is seemingly derived from primitive pulmonary epithelium. As per the molecular
studies, a monoclonal pattern has been demonstrated in round and surface cells. AKT1
internal tandem duplications, point mutations, and short indels have been recognized
in nearly all sclerosing pneumocytomas.[1]
[5] Shin et al[5] have reviewed clinicoradiological characteristics of 76 cases of PSP. The median
age was 50 years, and 88.2% of patients were females. Only 7.9% patients were symptomatic
for the mass and had hemoptysis, while in 71% it was incidentally detected and in
21.1% it was detected during workup for metastasis for other malignancy. Great majority
of the patients had single lesion (92.1%) and the mean diameter was 2.27cm. The cases
with size more than 3cm, with irregular borders, were more prone for being misdiagnosed
as lung cancer. Rarely, lymph node metastases can also happen.[5]
Four histological patterns can be seen in typical PSP: papillary, sclerotic, solid,
and hemorrhagic.[3] The papillary and solid histological pattern can be misdiagnosed as papillary NSCC-ADC
and carcinoid, especially on frozen section or small diagnostic biopsy.[1] Judicious IHC panel is helpful for resolving the differential diagnosis of papillary
ADC and carcinoids of lung (See [Table 1] for differenttial diagnosis). TTF1 is expressed in both surface epithelial and stromal
cells of PSP and it is also positive in papillary ADC and carcinoid tumors of lung,
hence can be misleading. In PSP, cuboidal surface and round stromal cells are both
epithelial membrane protein (EMA) and TTF1 positive. Pancytokeratin, CK7, Napsin A
stain surface cells and the round stromal cells are either negative or weakly positive.
Differential and contrast immunostaining of surface epithelial cells and negative-to-weak
positive immunoexpression in stromal cells by CK are very helpful for confirmation.
Table 1
Radiological and pathological features of different entities
|
Entity
|
Radiological
|
Histological
|
IHC
|
|
Pulmonary sclerosing pneumocytoma
|
No distinct radiological features have been described in literature; however, some
CT signs may be useful such as the marginal pseudocapsule sign, the most common sign
|
Well-circumscribed tumor with varied growth patterns: papillary, solid, sclerotic,
and hemorrhagic
The tumor had two cell types—cuboidal surface cells and oval-to-round stromal cells.
The cuboidal surface cells are similar to type II pneumocytes and the round cells
are small with central bland nuclei. No significant cytologic atypia or nuclear pleomorphism
seen. Mitosis is rare
|
Surface and round stromal cells are both epithelial membrane protein (EMA) and TTF1
positive.
Pancytokeratin, CK7, Napsin A stain surface cells but the round stromal cells are
negative or weakly positive
|
|
Papillary adenocarcinoma of lung
|
No distinct radiological features have been described in literature
|
The tumor consists of neoplastic glandular cells growing along the surface of fibrovascular
cores. The neoplastic cells display significant cytologic atypia, nuclear pleomorphism
and frequent mitosis
|
Tumor cells are CK, TTF1 and Napsin A positive
|
|
Carcinoid tumor of lung
|
Central tumors are usually seen as a single hilar or perihilar mass that is usually
well-defined, often marked homogeneous contrast enhancement due to high vascularity;
calcification (usually eccentric) can occur but is not a common feature
|
Various organoid growth patterns with trabecular, rosette formation, palisading, ribbon,
or solid arrangements. Papillary and true glandular patterns can be seen
Tumor cells are monotonous uniform, fine granular chromatin, inconspicuous nucleoli
Graded according to mitosis and necrosis
|
Tumor cells are CK, synaptophysin, chromogranin, CD56, and INSM1 positive
TTF1 tends to be positive in peripheral carcinoids but negative in central tumors
|
Abbreviations: CT, computed tomography; IHC, immunohistochemistry; TTF1, thyroid transcription
factor 1.
Detailed clinical history, diligent histomorphological, and IHC examination espoused
with correlation of clinical and radiological findings like absence of significant
lymphadenopathy as evaluated in the presented case are imperative as PSP is treated
by surgical resection alone that is considered as curative.[1]
[3]
[4]
