Focal cirrhosis of the liver: Its relation to the so-called hamartoma (adenoma, benign hepatoma)

  • View

  • Download

Embed Size (px)

Text of Focal cirrhosis of the liver: Its relation to the so-called hamartoma (adenoma, benign hepatoma)





    OCAL OR SOLITARY NODULAR hiAssu are oc- F casionally observed in human livers that show no other significant pathological changes. These include metastatic neoplasms, an occa- sional primary hepatic-cell carcinoma, focal subcapsular hyperplasia of bile ducts, heman- giomas, granulomas, and adrenal rests. In addi- tion there is the lesion that has been reported under a variety of names such as adenoma. hamartoma, benign hepatoma, solitary hyper- plastic nodule, and focal cirrhosis. This lesion occurs in both sexes and at any age. It is usually solitary but may be multiple and varies in size from a diameter of a few millimeters to several centimeters. I t is seen by the surgeon when its size is great enough to cause a palpable abdomi- nal mass. More frequently it does not cause the patient any disturbance and occurs as an incidental finding at laparotomy or the post- mortem examination, in which cases it must be distinguished from metastatic cancer and pri- mary carcinoma of the liver. Despite the multi- plicity of terms that have been used to denote this entity in the literature, the pathological descriptions, photographs, and clinical behav- ior of the lesion have been strikingly similar. Our present knowledge of the subject is based largely on isolated case reports. No investiga- tions of the problem have included a sufficient number of cases to justify any conclusions re- garding histogenesis.

    The present communication is based on a study of thirty-four examples of this entity that were found at necropsies performed at the Mayo Clinic. These cases not only provided am- ple material for the investigation of the fully developed phases of the lesion but also afforded the opportunity to observe the earliest stages of its development. This study was undertaken in an attempt to follow the development of the lesion in question and possibly to elicit infor- mation of value in understanding its histogene- sis, classification, and possible relationship to

    From the Mayo Foundation and the Section on Patho- logic Anatomy, Mayo Clinic, Rochester, Minnesota.

    Received for publication, January 16, 1955.

    primary hepatic-cell carcinoma occurring in the absence of generalized cirrhosis.


    The problem of differentiating localized nodular hyperplasia in the liver from true neo- plasm was discussed as early as 1884 by Sim- monds. At necropsy he found, as an incidental lesion, a localized oval mass in the left lobe of the liver. The remainder of the liver was normal. In his discussion, he regarded the nod- ule as a peculiar response of the liver to in- jury but suggested that i t might have been congenital in origin. Ribbert, Yamagiwa, and Pepere also suggested that these adenomas of the liver were a congenital malforma- tion consisting of a separation of a group of cells from continuity with the rest of the organ or a dislocation from bile ducts. In Schmellings case, there were multiple ham- artomas associated with hypospadias, bilateral syndactylia of the toes, and bilateral hydroceles. Shaw and Turner in separate publications re- ported the same case, which was called an ade- noma (hepatoma) but which had a close re- semblance to a localized area of cirrhosis. Shaw stated that these lesions occurred in childhood, were solitary, were commoner in the right lobe of the liver than in the left, and were found in the absence of cirrhosis.

    The relationship of these adenomas to pri- mary carcinoma of the liver was mentioned by Milne who suggested that they might be en- capsulated cancer growths. Wright reported a case of a man, aged 60 years, from whom an or- ange-sized mass in the right lobe of the liver was removed. This mass was encapsulated and lay in a surrounding area of cirrhosis, though the rest of the liver showed no cirrhotic change. Although the lesion was considered to be a primary carcinoma, the patient was alive and well three years later. The possibility of neo- plastic change arising from benign hepato- mas has been discussed by Hoffman and by Franklin and Downing.


  • 744 CANCER July 1953 Vol. 6


    Surg. Age or

    Author Cases Sex necr. Size, cm. Lobe Diagnosis Comment

    Wallace, 1941

    Benson & Penber- thy, 1942

    Hoffman, 1942

    Sierra & Ardao, 1944

    Branch, Tonning Pr Skinner, 1945

    van Prohaska, 1945

    Hershey, 1946

    Duckett 8; Mont- gomery, 1947

    Franklin & Down- ing, 1947

    ando. 1947 Pasquale & Ferdin-

    Patton; 1948

    Hunter, 1949

    Greinacher, 1950

    Kay Pr Talbert, 1950

    McBurney, Woolner & Wollaeger, 1950

    Bartlett & Shellito, 1951

    Gerding, Popp & Martineau, 1951

    Josephy, 1951

    Roth, 1951




















    23 S F

    7mo. S F 38 S F 41 S F 32 S F 47 s M

    14 S F 73 s M 3 s

    A1 20 mo. S

    23 S M 56 S F

    16% mo. s F 28 s F

    7%mo. N F

    8mo. N F 67 N M

    7mo. S F 13 S M

    28 S F


    22 mo. S F

    8 s R.I 88 N M 35 s F

    15X13X.5 Rt. Hepatoma

    6 diam. Rt. Hamartoma

    7.5 diam. Rt. Benign hepatoma

    7 x 5 x 5 Rt. Adenonia

    6 diam. Lt. Adenonia

    wt. 240 gm. Lt. Chronic focal hepatitis

    10 diam. Lt. Hepatorna (adenoma)

    18X17X8.5 Lt. Benign hepatoma

    ? Rt. Pr Lt. Benign hepa toina

    3 . 5 X 1 Rt. Adenoma with malignant tendencies

    13 diam. Rt. Benign hepatoma

    wt. 760 gm. Lt. Solitary adenoma

    17X17X9 .5 Rt. Hamartoma

    5.6X5X1.9 Lt. Benign hepatoma

    ? Rt. Hamartoma

    ? Rt. Hamartoma

    ? Rt. 7

    9.5 X 7.5 X 6 Caud. Hamartoma

    7 LRt. & Lt. Harmatoma

    6X4X3 Lt. Solitary hyperplastic nodule

    1 6 X 1 5 X 8 Rt. Hamartoma

    Rt. & Lt. Cholangio- hepatoma


    12 diam.

    1 2 X 9 X 9 Lt. Benign

    11 .5X lOX5 ? Adenoma

    Patient alive and well 5 yr. postop.

    Noted resemblance to cir- rhosis

    Noted resemblance to cir- rhosis

    Noted resemblance to cir- rhosis

    Suspected a t operation as a metastasis (patient had multiple primary carcinomas)

    Specimen not completely removed-recurrence

    Follow-up not noted


    Cyst in lesion

    Calls attention to- possi- bility of lesion being a reparative process

    Necrosis in mass

    Question of carcinosar- coma

    Incomplete removal a t op- eration

    Biopsy only-called atten- tion t o resemblance to cirrhosis

    History of hepatitis

    Adenoma with marked fibrous displacement

    Noted resemblance to cir- rhosis

    Alcoholic history

    Found incidental to hy- sterectomy

    In 1904, Albrecht introduced the term ham- artoma, which was defined as a tumor-like malformation in which actually can be seen only an abnormal mixture of normal elements of the organ in which they appear, whether it be in amount, arrangement, or the degree of maturity, or in all of these aspects. This term was subsequently applied to many solitary inasses in the liver whose descriptions fit the

    adenomas and hepatomas of many authors. McBurney and associates described a lesion

    identical in its salient features with the major- ity of cases described by others as adenomas, hepatomas, or hamartomas but they rejected a neoplastic concept by a diagnosis of solitary hyperplastic nodule. Previously Huguenin had suggested the possibility of a focal cirrho- sis, a term later used by Stewart and associates

  • No. 4 FOCAL HEPATIC CIRRHOSIS AND HAMARTOMA - Benz 6 Baggenstoss 745 to describe a nodule in an otherwise noncir- rhotic liver.

    Warvi discussed criteria for distinguishing adenomas (hamartomas) from localized nodu- lar hyperplasia. T h e distinction depended upon such features as the presence or absence of encapsulation, bile ducts, and secretion of bile-criteria that have not been, and probably could not be, adhered to in individual cases reported in the literature.

    Our review of the literature prior to 1940 (lid not disclose any well-documented cases that were not considered by Keller, Warvi, or Hoff inan in their comprehensive reviews of the subject. Cases recorded since 1940 pertinent to this comniunicatioii in which there was adequate docunientation are summarized in Table 1.


    Cases selected for this study were obtained from the records of necropsies at the Rlayo Clinic over a period of thirty years (1922 to 1951). All cases in which there was generalized cirrhosis were excluded. Histological sections of focal lesions in noncirrhotic livers recorded in the protocols as aclenoma, hepatoma, hamar- toma, localized regenerative hyperplasia, or focal cirrhosis were examined. In this group were numerous nodules recorded as bile-duct adenomas that were actually subcapsular col- lections of proliferating bile ducts morphologi- cally similar to those described by Edwards and White in rats. These were excluded from this study.

    Thirty-four cases occurred in which the hepa tic lesions, though usually smaller than lesions seen surgically, were consistent with those cases in the literature in which a diagnosis of adenoma, hamartoma, benign hep- atoma, or solitary hyperplastic nodule was made. Histories were reviewed in all cases. Gross specimens containing the lesions were available for study in twenty cases, and, in the majorit