Pulmonary Chondromatous Hamartomas

Pulmonary Chondromatous Hamartomas* Report of Seventeen Cases and Review of the Literature

T. ]. Poirier, M.D. 00 and HowardS. Van Ordstrand, M.D .• F.C.C.P.t

Pulmonary chondromatous hamartomas constitute the most common benign lung tumor. They are reported to account for 8 percent of all coin lesions. They usually present as an asymptomatic so6tary circumscribed coin lesion from 1 to 4 em in diameter, but they may occur as a large mass within the pulmonary parenchyma or within the pleural cavity. Approximately 8 percent are endobronchial in origin. Between 1954 and 1969, 17 chondromatous hamartomas were discovered and treated at the Cleveland C6nic, two of which had Rigler's umbi6cation sign on laminagrams. A review of the 6terature is presented.

H amartomas, as originally described by Albrecht

and five women. All of the 16 patients with parenchymal chondromatous hamartomas were asymptomatic at the time of discovery of the coin lesion on routine chest roentgenogram. On the other hand, our one patient with an endobronchial lesion presented with fever, dyspnea, wheezing, and hemoptysis. His chest roentgenogram revealed left lower lobe infiltrate. Bronchoscopy revealed a 2 x 3 em mass partially obstructing the left upper lobe orifice and completely obstructing the left lower lobe orifice. Pneumonectomy was performed because the entire left qpper lobe had been destroyed by obstructive emphysema and the left lower lobe had been destroyed by bronchiectasis.

1

in 1904, are tumor-like malformations composed of an abnormal mixture of the normal constituents of the organ in which they are found. These constituents may include fibrous tissue, fatty tissue, myxomatous tissue, epithelial tissue, smooth muscle, and cartilage. The mixture of these tissues may vary with regard to quantity, arrangement, degree of differentiation, or any combination of these characteristics. Chondromatous hamartomas, as the name implies, always include cartilage; they comprise the majority of pulmonary hamartomas. The remainder are in the category of either vascular hamartomas or hamartomas composed of the above-mentioned tissues in various combinations. An example of the latter group is a fibroleiomyomatous hamartoma. This report concerns the characteristics of only the chondromatous hamartomas.

Location and Size Nine lesions were in the left lung and eight were in the right lung. Fourteen of the 17 were from 1 to 4 em in diameter. Patient 8 in our series presented with an asymptomatic 8 x 7 em mass in the right middle lobe. Laminagrams revealed it to be a solid non-calcified tumor separate from the mediastinum ( Fig 1A and B).

CLINICAL FEATURES

Age, Sex Ratio, and Symptoms Table 1 lists the clinical, radiologic, and surgical features of the 17 patients treated at this institution. The average age was 50 years. There were 12 men

PATHOLOGIC FEATUBES

•From the Deparbnent of Pulmonary Disease, The Cleveland Clinic Foundation, Cleveland, Ohio. ••Fellow, Deparbnent of Internal Medicine. tchairman, Division of Medicine; Head, Department of Pulmonary Disease.

The gross appearance of the chondromatous hamartoma , in our series of patients was a firm, lobulated mass that separated easily from the sur-

50

51

PULMONARY CHONDROMATOUS HAMARTOMAS Table I --Clinical Findin11• and Operalif1e Procedure• Case No 1 2 3 4 5 6 7 8 9 10 ll

12 13 14 15 16 17

Age, Sex

Size (em)

Location

Roentgenographic Evidence of Calcium

Surgical Procedures

45, M 61, M 43, M 48, M 50,M 54,M 65, M 64, F 47, F 51, F 62, F 36, F 43, M 48, M 37, M 52, M 52, M

6x5x4 3.1 X 1.2 X 0.6 2.0 X 2.5 X 2.5 1.2 1.5 X 1.0 X 1.5 2.5 X 2.2 X 1.2 2.5 X 1.5 X 0.2 8.0 X 7.0 1.2 X 1.0 8.0 X 5.0 X 1.0 1.7 X 1.3 2.0 X 1.5 X 1.0 1.5 4.0 X 2.5 2.3 X 2.2 X 1.5 1.5 X 1.5 X 1.0 1.0

RLL RLL LLL RUL LUL LUL RML RML RML LLL LUL LLL LLL RUL LUL Bronchus, Left RUL

No No No No No No No No No No No No No Yes No No No

Lobectomy Enucleation Enucleation Wedge Resection Enucleation Enucleation Enucleation Lobectomy Enucleation Wedge Resection Enucleation Wedge Resection Enucleation Lobectomy Wedge Resection Left Pneumonectomy Enucleation

rounding lung tissue. The cut surface was graywhite with occasional small cystic areas (Fig 2A and B). The microscopic appearance was variable, depending upon the proportion of the type of tissue in the tumor. Figure 3 illustrates the usual microscopic appearance of the type lesion seen in our patients. Figure 4 demonstrates the predominant peripheral location of the epithelial clefts usually present in a chondromatous hamartoma. RoENTGENOGRAPmc

FEATURES

Of the 17 patients, only one had evidence of

calcium on the routine chest roentgenogram. Laminagrams in seven patients did not show evidence of calcium. However, of those seven patients, in two, the tomograms revealed a Rigler's umbilication sign (Fig 5A and B; and 6A and B). DISCUSSION AND REVIEW OF THE LITERATURE

Although convenient to use, the term hamartoma should not be used to designate all pulmonary hamartomas. As originally used by Albrecht 1 in 1904, the term applied only to tumor-like malformations of the spleen, breast, liver, and kidney. Two years later Hart2 discovered these in the lung. Since

FIGURE lA and B. Asymptomatic chondromatous hamartoma, 10 em in diameter.

CHEST, VOL. 59, NO. 1, JANUARY 1971

52

POIRIER AND VAN ORDSTRAND

FIGURE

2A and B. Typical gross appearance of chondromatous hamartomas of various sizes.

then, there has been much disagreement as to the precise nomenclature. Such terms as chondroadenoma, a hamartochondroma, 4 lipochondroadenoma, 5 bronchioma, 6 mixed tumors of the lung, 7 and chondromatous hamartoma 8 have been used. We have used the latter term because it best

describes these cartilaginous tumors. For tumors without cartilage we use the terms vascular hamartomas, as seen in Rendu-Osler-Weber disease, and non-cartilaginous hamartomas. All of the cases of multiple pulmonary hamartomas reported to date have been of the non-cartilaginous type. n-12

FIGURE 3. Cross section of a typical chondromatous hamartoma composed of cartilage, fatty tissue, loose connective tissue, and clefts lined by epithelium.

FIGURE 4. Photomicrograph of an area from the edge of an intrapulmonary cartilage-containing tumor, showing the peripheral location which the epithelial clefts usually adopt.

CHEST, VOL. 59, NO. 1, JANUARY 1971

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PULMONARY CHONDROMATOUS HAMARTOMAS

FIGURE

sign.

SA and B. Laminagrams of chondromatous hamartomas revealing Rigler's umbilication

Because chondromatous hamartomas usually present as coin lesions, they are included in the reports reviewing coin lesion. Jones and Cleve13 reviewed the series of 12 separate reports on isolated circumscribed lesions of the lung. Of the 714 total number of cases, 57 (8 percent) were hamartomas. Those 57 hamartomas accounted for 64 percent of all benign tumors in the 12 reports. Davis et aP 4 reviewed more than 1200 solitary circumscribed nodules less than 6 em in diameter and found 8.5 percent were hamartomas. The average age recorded in most large series is 45 to 50. The age span is from newborn to age 76.

FIGURE

sign.

Table 2 compares our findings to those of recent reports. Gudbjerg 15 reported ten patients, three of whom were less than ten years of age. Jones 16 reported a case of a 3.5 em hamartoma of the right upper lobe discovered in a newborn delivered during the 28th week of pregnancy. Tissue sections revealed cartilage in small nests within the islands of fibrous connective tissue. Symptomatic parenchymal chondromatous hamartomas are unusual. However, those patients with an endobronchial lesion often present with fever, wheezing, or hemoptysis. Extensive surgery is the rule in these patients because of the destructive

6A and B. Laminagrams of chondromatous hamartomas revealing Rigler's umbilication

CHEST, VOL. 59, NO. 1, JANUARY 1971

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POIRIER AND VAN ORDSTRAND Table 2--Feature• of Chondromatou• Hamartoma. Pre11iou•l:r Reported: A compori•on with thi• report

Author

Patients in Series

Lemon and Good28 Blair and McElvin29 Le Roux30 Oldham et aJIS Poirier and Van Ordstrand

17 25 27 30 17

Age Span (Years)

Average Age

Roentgenographic Calcium

21 to 62 14 to 76 30 to 64 13 to 67 36 to 65

45 45

II

49 50

changes which frequently accompany bronchial obstruction. The majority of chondromatous hamartomas are found within the pulmonary parenchyma. The incidence of endobronchial chondromatous hamartomas is usually stated as 19.5 percent. Bateson 17 obtained this incidence by reviewing 159 papers containing the reports of 457 cartilage-containing pulmonary tumors. Because of the natural tendency to report unusual lesions, many of these 159 papers dealt exclusively with endobronchial lesions. We feel a more accurate incidence can be arrived at by reviewing the series of only large institutions. In doing so, we found an incidence of less than 8 percent (Table 2). Peripheral chondromatous hamartomas usually present as a well-circumscribed asymptomatic coin lesion. On the other hand, those that present as mass lesions are almost always symptomatic. Oldham and colleagues 1 ~' described a 13-year-old boy who presented with sharp chest pain. Chest roentgenograms showed a large, ill-defined mass in the right lower lobe containing mottled calcifications. At surgery an extralobar tumor 14 em in diameter was excised. Microscopic sections were characteristic of chondromatous hamartoma. Gluck and Moser 1 9 reported a chondromatous hamartoma which presented as an irregular lobulated mass adjacent to the mediastinum and left hilum. Tomograms could not definitely separate it from the mediastinum. At surgery, a mass 9 em in diameter was excised from the pulmonary parenchyma. Finally, Jackson et al 20 reported two cases of massive cystic hamartomas which contained cartilage. The surgical specimens measured 17 x 15 x 12 em and 16 x 14 x 10 em respectively. The former tumor was resected from a 54-year-old woman who for the past four years had undergone repeated thoracenteses for relief of dyspnea. The second specimen was obtained from a 27-year-old man who had documented existence of a pulmonary cyst for at least 11 years. The pathologic features of chondromatous hamartomas a.re essentially those noted in our series. Bateson 1 7 stressed that the peripherally located epithelial clefts account for the ease with which these

Location L R 13

4

II

6 15 9

17 19 21 12

I

25 4

19 13 8

Sex M F 6 8 8 9 5

Percentage Endobronchial 0 8 7.4 3.3 5.9

tumors are enucleated from surrounding tissue. There are no radiologic features pathognomonic of chondromatous hamartomas. The presence of punctate calcifications, while helpful, is not diagnostic. The typical appearance is a well-circumscribed coin lesion which may or may not possess calcium. The presence of a Rigler's 21 sign in a hamartoma has never been reported previously according to our review of the literature. We did note that Drevvatyne and Fremann-Dahl 22 reported finding this sign in 16 or 22 tuberculomas. Described in 1955, this sign which is described as a "notching or umbilication of a border of the shadow," has come to be accepted as indicative of malignancy. In view of the above findings, we believe that this sign should no longer be considered pathognomonic of malignancy. The origin of chondromatous hamartomas is not clearly known. Hodges 23 has discussed the prevailing etiologic theories, namely: 1) congenital malformation, 2) hyperplasia of normal structures, 3) neoplasia, and 4) response to inflammation. Most authors believe that hamartomas originate from congenital malformations, that is, from connective tissue cell rests of bronchiole walls, which have the potential of forming any of the tissue components seen in a chondromatous hamartoma. A definite diagnosis of chondromatous hamartoma is usually made only after thoracotomy. Some coin lesions as seen on chest roentgenograms are so labeled on the basis of punctate calcifications plus the lack of growth over several years. The presence of both of these criteria is necessary to exclude a malignancy, since calcium has been reported in a number of carcinomas of the lung. By contrast, growth of coin lesions does not exclude the diagnosis of chondromatous hamartoma. Several authors have reported cases demonstrating growth of these lesions.:~-24-26 Jenson and Schiodt 27 reported a twofold increase in size during a two-year observation period. The usual therapy for pulmonary chondromatous hamartomas is surgical removal. Because of the ease with which these lesions are enucleated, that is the most frequently used procedure. For those with an CHEST, VOL. 59, NO. 1, JANUARY 1971

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endobronchial location, removal is by either bronchoscopy or bronchotomy. Once removed, these tumors do not recur. REFERENCES

1 Albrecht E: Ueber Hamartome. Verhandl Deutsch Path Gessellsch 7: 153, 1904 2 Hart: Ueber die primaren Enchondrome der Lunge. Ztschr Krebsforsch 4: 578, 1906 3 Adams MJ: Pulmonary hamartoma. Thorax, 12: 268, 1957 4 Bateson EM, Abbott EK: Mixed tumors of the lung or hamarto-chondromas. Clin Radiol, 11: 232, 1960 5 Brewin EG: A case of lipoma of the bronchus treated by transpleural bronchotomy. Brit J Surg, 40: 282, 1952 6 Aletrag A, Bjork VO, Fors B: Benign bronchopulmonary neoplasms. Dis Chest 44: 498, 1963 7 Ehrenhaft JL, Womack NA: Mixed tumors of the lung. Ann Surg 136: 90, 1950 8 Carlsen CJ, Kiaer W: Chondromatous hamartoma of the lung. Thorax 5: 283, 1950 9 Keers RY, Smith FA: A case of multiple hamartomata of unusual type. Brit J Dis Chest, 54: 349, 1960 10 Logan WD, Rohde FC, Abbott OA, et al: Multiple pulmonary fibroleiomyomatous hamartomas. Amer Rev Resp Dis 91: 101, 1965 11 Madani MA, Dafoe CS, Ross CA: Multiple hamartomata of the lung. Thorax 21: 468, 1966 12 Spotnitz M, Hopeman AR: Multiple pulmonary hamartomas. Dist Chest 51:645, 1967 13 Jones RC, Cleve EA: Solitary circumscribed lesions of the lting. Arch Intern Med 93:842, 1954 14 Davis EW, Peabody JW, Katz S: The solitary pulmonary nodule. J Thoracic Surg 32: 728, 1956 15 Gudbjerg CE: Pulmonary hamartomata. J Roentgenol86: 842, 1961

16 Jones CJ: Unusual hamartoma of the lung in a newborn infant. Arch Path 48: 150, 1949 17 Bateson EM: Relationship between intrapulmonary and endobronchial cartilage containing tumors. Thorax 20: 447, 1965 18 Oldham HN, Young WG, Sealy WC: Hamartoma of the lung. J Thorac Cardiovasc Surg 53: 735, 1967 19 Gluck MC, Moser KM: Hamartoma of the lung presenting as a mediastinal mass. Amer Rev Resp Dis 98: 281, 1968 20 Jackson RC, McDonald JR, Clagett OT: Massive cystic pulmonary hamartoma. J Thoracic Surg 31: 504, 1956 21 Rigler LG: A new roentgen sign of malignancy in the solitary pulmonary nodule. JAMA 157:907, 1955 22 Drevvatyne T, Fremann-Dahl J: Peripheral bronchial carcinomas-a radiologic and pathological study. Brit J Radiol 34: 180, 1961 23 Hodges FV: Hamartoma of the lung. Dis Chest 33: 43, 1958 24 Perry DC: Tracheo-bronchial and pulmonary chondroadenomas. Brit Med J 1: 1572, 1959 25 Weisel W, Glicklich M: Pulmonary hamartoma, an enlarging neoplasm. Arch Surg 71: 128, 1955 26 Sagel SS: Hamartoma, on occasion a rapidly growing tumor of the lung. Radiology 91:971, 1968 27 Jenson KG, Schiodt RS: Growth considerations of hamartomas of the lung, Thorax 13: 233, 1958 28 Lemon WE, Good AA: Hamartoma of the lung. Radiology 55: 692, 1950 29 Blair TC, McElvin RB: Hamartoma of the lung. Dis Chest 44: 296, 1963 30 LeRoux BT: Pulmonary hamartomata. Thorax 19: 236, 1964 Reprint requests: Dr. H. Van Ordstrand, Cleveland Clinic, 2020 East 93rd, Cleveland 44106

Central Nervous System in Sarcoidosis Sarcoidosis appears to represent a distinct entity, in all probability infectious; however, the agent remains unknown. Chronic meningitis occurs with predilection for the base of the brain, and sometimes causes hydrocephalus. Less often, central nervous system parenchyma is involved. Papilledema may appear. Any or all of the cranial and peripheral nerves may be involved, especially facial, next often optic (neuritis or neuroretinitis may lead to optic atrophy). Extraocular paresis may occur. Pituitary and hypothalamus may be affected; the sella may be enlarged. Degeneration of spinal cord tracts may follow nerve root lesions. Tumor-like masses may occur in relation to the dura. Histologically, tubercles are seen.

CHEST, VOL. 59, NO. 1, JANUARY 1971

Foreign body giant cells appear in fair numbers; they present vacuolated cytoplasm. The latter is essentially fatty and shows varying degrees of precipitation of crystalline material in various patterns, including star shapes (asteroid bodies). The substance inspissates and round, ovoid or clover-leaf laminated calcific bodies are formed; the outer lamellae are basophilic, the inner portions often being gray to colorless. The foregoing inclusion bodies, spicular as well as calcified, are characteristic of sarcoidosis, but are not unequivocally diagnostic. Dublin WB:Fundamentals of Nuropathology (2-nd ed). Springfield, C. C Thomas, 1967