Pulmonary hamartoma: a clinic-pathologic study of 206 consecutive cases focusing on different histologic variants

doi:10.3877/cma.j.issn.2095-8773.2022.03.01

中华胸部外科电子杂志 ›› 2022, Vol. 09 ›› Issue (03) : 133 -139. doi: 10.3877/cma.j.issn.2095-8773.2022.03.01

国际胸外科专栏/述评

Pulmonary hamartoma: a clinic-pathologic study of 206 consecutive cases focusing on different histologic variants

Laura Melocchi¹, Alberto Cavazza², Maria Sirolli³

^1. Pathology Unit, Department of Oncology, Fondazione Poliambulanza Hospital Institute, Brescia, Italy
^2. Pathology Unit, Azienda USL/IRCCS di Reggio Emilia, Reggio Emilia, Italy
^3. Pathology Unit, Santa Maria delle Croci Teaching Hospital, Azienda USL of Romagna, Ravenna, Italy；Resident of the School of Specialization in Anatomic Pathology "A.M. Mancini", University of Bologna, Bologna, Italy
^4. Operative Unit of Pathologic Anatomy, Azienda USL of Romagna, Infermi Hospital, Rimini, Italy
^5. Pathology Unit, Department of Oncology, Fondazione Poliambulanza Hospital Institute, Brescia, Italy；Specialty School of Pathologic Anatomy, University of Brescia, Brescia, Italy
^6. General and Thoracic Surgery Unit, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy；Department of Thoracic Surgery, Azienda USL of Romagna, Santa Maria delle Croci Teaching Hospital, Ravenna, Italy

收稿日期:2022-02-27 接受日期:2022-04-14 出版日期:2022-08-28

Pulmonary hamartoma: a clinic-pathologic study of 206 consecutive cases focusing on different histologic variants

Laura Melocchi¹, Alberto Cavazza², Maria Sirolli³

Received:2022-02-27 Accepted:2022-04-14 Published:2022-08-28

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Laura Melocchi, Alberto Cavazza, Maria Sirolli. Pulmonary hamartoma: a clinic-pathologic study of 206 consecutive cases focusing on different histologic variants[J]. 中华胸部外科电子杂志, 2022, 09(03): 133-139.

Laura Melocchi, Alberto Cavazza, Maria Sirolli. Pulmonary hamartoma: a clinic-pathologic study of 206 consecutive cases focusing on different histologic variants[J]. Chinese Journal of Thoracic Surgery(Electronic Edition), 2022, 09(03): 133-139.

Background:

Pulmonary hamartoma (PH) is the most common benign pulmonary tumor usually presenting as a solitary, well-demarcated nodule composed of mature cartilage and adipose tissue. Some unusual histologic variants are challenging on clinic-radiologic and pathologic examination.

Methods:

We collected a multicentric, retrospective, consecutive series of 206 PH with clinical characteristics and histologic variants.

Results:

Clinical data were in line with the literature demonstrating a male prevalence (2:1) and a median age of 61.6 years. The median size of the nodule was 17.8 mm. When performed, SUVmax >2.5 at FDC-PET was evidenced in 4% of cases (5 out of 119) and was significantly associated with undifferentiated/myxoid histology. Conventional histology showing chondroid or chondro-lipomatous PH was quoted in 186 cases (90%), while leiomyomatous and undifferentiated/myxoid variants were recorded in 20 cases (10%). The high rate of unusual variants on pathology is possibly related to a selection bias due to external consultations or surgical excision of the lesions lacking classic features at imaging studies.

Conclusions:

About 10% of PH may show unusual histology and SUVmax >2.5 at FDC-PET in 4%. These uncommon findings may challenge the correct recognition, raising some concerns in terms of differential diagnosis with several other mesenchymal tumors in the lung. These features should be kept in mind to achieve a correct diagnosis and avoid unnecessary invasive treatments.

关键词: Hamartoma, lung, WHO, histology, immunohistochemistry, incidence, imaging

Table 1 Summary of clinicopathological features of pulmonary hamartoma

Features		Pulmonary hamartoma (n=206)
Sex, n (%)
	Male	136 (66)
	Female	70 (34)
Age (years), mean (range)		61.6 (46-81)
Size (mm), mean (range)		17.8 (8-55)
Site, n (%)
	Right upper lobe	51 (25)
	Right middle lobe	4 (2)
	Right lower lobe	63 (30)
	Left upper lobe	43 (21)
	Left lower lobe	45 (22)
Slides number per case, mean (range)		2.5 (2-8)
Intraoperative examination, n (%)		37 (18)
	Hamartoma	32 (86.5)
	Deferred	5 (13.5)
	Other	-
Histology
	Chondroid/lipomatous	129 (62.3)
	Chondroid	57 (27.7)
	Myxoid	12 (6)
	Leiomyomatous	8 (4)
	Multifocality	-
Surgical procedure, n (%)
	Wedge resection	68 (33)
	Enucleation	130 (63)
	Segmentectomy	7 (3.5)
	Lobectomy	1 (0.5)
PET with 2-deoxy-2-[fluorine-18] fluoro-D-glucose, n (%)		119/206 (58)
SUVmax index, n (%)
	<2.5	114/119 (96)
	>2.5	5/119 (4)

Table 1 Summary of clinicopathological features of pulmonary hamartoma

Features		Pulmonary hamartoma (n=206)
Sex, n (%)
	Male	136 (66)
	Female	70 (34)
Age (years), mean (range)		61.6 (46-81)
Size (mm), mean (range)		17.8 (8-55)
Site, n (%)
	Right upper lobe	51 (25)
	Right middle lobe	4 (2)
	Right lower lobe	63 (30)
	Left upper lobe	43 (21)
	Left lower lobe	45 (22)
Slides number per case, mean (range)		2.5 (2-8)
Intraoperative examination, n (%)		37 (18)
	Hamartoma	32 (86.5)
	Deferred	5 (13.5)
	Other	-
Histology
	Chondroid/lipomatous	129 (62.3)
	Chondroid	57 (27.7)
	Myxoid	12 (6)
	Leiomyomatous	8 (4)
	Multifocality	-
Surgical procedure, n (%)
	Wedge resection	68 (33)
	Enucleation	130 (63)
	Segmentectomy	7 (3.5)
	Lobectomy	1 (0.5)
PET with 2-deoxy-2-[fluorine-18] fluoro-D-glucose, n (%)		119/206 (58)
SUVmax index, n (%)
	<2.5	114/119 (96)
	>2.5	5/119 (4)

Figure 1 A Leiomyomatous pulmonary hamartoma of the right lower lobe at comuted tumography. The lesion consists of a peripheral, well-defined nodule lacking calcification or fat density.

Figure 2 A conventional pulmonary hamartoma predominantly consisting of regular chondroid and adipose tissue centrally entrapping a bronchiolar structure (haematoxylin-eosin stain, ×125).

Figure 3 A pulmonary hamartoma consisting of undifferentiated mesenchymal tissue entrapping alveolar structures and forming papillary-like formations (haematoxylin-eosin stain, ×100).

Figure 4 A leiomyomatous pulmonary hamartoma showing a benign smooth muscle proliferation entrapping alveolar structures and creating papillary-like formations (haematoxylin-eosin stain, ×200).

Table 2 A concise summary of the clinic-pathologic helpful features of tumor in differential diagnosis with pulmonary hamartoma

Tumor type	Gender	Specific clinical features	Morphology	Ancillary techniques
Hamartoma	Male > female	Peripheral > endobronchial		HMGA2-LPP fusion gene due to the translocation t(3;12)(q27-q28; q14-q15), consisting of exons 1-3 of HMGA2 and exons 9-11 of LPP. HMGA2 is consistently expressed in hamartoma and lipoma
Chondroma	Females in Carney's triad; male prevalence in sporadic form	Multiple nodules in Carney's triad; peripheral (very rare endobronchial site)	Well-circumscribed nodule with fibrous pseudocapsule, hyaline cartilage with/without bone metaplasia and/or calcification; lack of entrapped epithelium	SDHB deficiency and expression
Adenofibroma	Female > male	Peripheral	Leaf-like projections lined by cuboidal/columnar epithelium and acellular, sclerotic stroma with/without calcifications and alveolar entrapping	No specific markers
Intrapulmonary solitary fibrous tumor	No predilection	Peripheral	Tumor growth of spindle cells generally alternating hypo-and hypercellularity in various areas of the lesion	STAT6 (product of NAB2-STAT6 gene fusion) and CD34 expression
Benign metastasizing leiomyoma	Female	Past or current history of uterine leiomyomas; peripheral nodule/s	Solid proliferation of smooth muscle spindle cells lacking significant atypia or mitotic rate entrapping alveolar structures at the periphery	Expression of smooth muscle markers, hormonal receptors
Inflammatory myofibroblastic tumor	No predilection	More frequent in childhood	Ill-defined proliferation of spindled myofibroblasts with/without ganglion-like cells intermingled with inflammatory infiltrate (plasma cells, lymphocytes and eosinophils), also entrapping alveoli with hyperplastic pneumocytes	Expression of smooth muscle markers. ALK1 expression in a subset with ALK1 gene rearrangement. Increase of IgG4 positive plasma cells in myofibroblastic proliferation secondary to IgG4 syndrome

Table 2 A concise summary of the clinic-pathologic helpful features of tumor in differential diagnosis with pulmonary hamartoma

Tumor type	Gender	Specific clinical features	Morphology	Ancillary techniques
Hamartoma	Male > female	Peripheral > endobronchial		HMGA2-LPP fusion gene due to the translocation t(3;12)(q27-q28; q14-q15), consisting of exons 1-3 of HMGA2 and exons 9-11 of LPP. HMGA2 is consistently expressed in hamartoma and lipoma
Chondroma	Females in Carney's triad; male prevalence in sporadic form	Multiple nodules in Carney's triad; peripheral (very rare endobronchial site)	Well-circumscribed nodule with fibrous pseudocapsule, hyaline cartilage with/without bone metaplasia and/or calcification; lack of entrapped epithelium	SDHB deficiency and expression
Adenofibroma	Female > male	Peripheral	Leaf-like projections lined by cuboidal/columnar epithelium and acellular, sclerotic stroma with/without calcifications and alveolar entrapping	No specific markers
Intrapulmonary solitary fibrous tumor	No predilection	Peripheral	Tumor growth of spindle cells generally alternating hypo-and hypercellularity in various areas of the lesion	STAT6 (product of NAB2-STAT6 gene fusion) and CD34 expression
Benign metastasizing leiomyoma	Female	Past or current history of uterine leiomyomas; peripheral nodule/s	Solid proliferation of smooth muscle spindle cells lacking significant atypia or mitotic rate entrapping alveolar structures at the periphery	Expression of smooth muscle markers, hormonal receptors
Inflammatory myofibroblastic tumor	No predilection	More frequent in childhood	Ill-defined proliferation of spindled myofibroblasts with/without ganglion-like cells intermingled with inflammatory infiltrate (plasma cells, lymphocytes and eosinophils), also entrapping alveoli with hyperplastic pneumocytes	Expression of smooth muscle markers. ALK1 expression in a subset with ALK1 gene rearrangement. Increase of IgG4 positive plasma cells in myofibroblastic proliferation secondary to IgG4 syndrome

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