Familial angiolipomatosis is a rare syndrome that may be confused clinically with neurofibromatosis type 1. This condition is most often inherited in an autosomal recessive manner; however, several reports have been published suggesting an autosomal dominant mode of inheritance. Angiolipomatosis, although somewhat disfiguring, is a benign condition with no known association with malignant neoplasms. This is in contradistinction to neurofibromatosis, an autosomal dominant syndrome associated with a myriad of benign and malignant neoplasms. It is, therefore, important to discriminate this entity from neurofibromatosis when a patient presents with multiple subcutaneous tumors and a family history of similar lesions. Described is a case of a prison inmate with a history of seizures and “neurofibromatosis” without clinical documentation. Lisch nodules were noted on the irides. Postmortem examination showed multiple subcutaneous yellow tumors on the chest and arms. Fine-needle aspiration of 1 mass yielded adipose tissue with prominent vessels; histologic sections of another mass showed angiolipoma. The remainder of the autopsy showed significant coronary artery disease and a remote cerebral infarction of the temporal lobe but no signs of neurofibromatosis. We feel that the presence of multiple angiolipomas in combination with Lisch nodules lends credence to the proposed relationship between fatty tumors and neurofibromatosis suggested by other authors.
Angiolipomas are benign mesenchymal neoplasms characterized by mature adipose tissue with an admixture of capillaries often containing fibrin thrombi. These lesions may present as either singular or, more frequently, multiple subcutaneous masses.1–4 Although angiolipomas most often occur sporadically, other family members may be affected in a minority of cases.2 Familial angiolipomatosis may be inherited in either an autosomal recessive or an autosomal dominant fashion.5–7
Described is a case of a prison inmate who was found dead in his cell. There were multiple subcutaneous masses involving the chest wall and arms. Upon incarceration he stated that he had “neurofibromatosis”; there had been no clinical workup to support this diagnosis. Postmortem examination confirmed the presence of angiolipomatosis with no lesions to suggest neurofibromatosis other than Lisch nodules in the irides. A family history was obtained supporting an autosomal dominant syndrome.
REPORT OF A CASE
The decedent was a 42-year-old white man with a long history of ethanol abuse, seizures, and presumed neurofibromatosis. He was found dead in his prison cell kneeling against his bed with his hand pressed against his chest; there was no evidence of trauma. An autopsy was performed.
External examination revealed pigmented iris hamartomas (Lisch nodules) bilaterally (Figure 1); these were not sampled for histologic study. Numerous subcutaneous masses ranging from 1 to 3 cm in greatest dimensions were distributed over the forearms and wrists accompanied by healed surgical scars. Three 1 to 3-cm, soft, subcutaneous nodules were noted on the anterior chest wall. The remainder of the external examination was essentially unremarkable.
A 20-gauge needle was used to aspirate 1 of the subcutaneous nodules from the left arm. The smear consisted of mature adipose tissue with rare capillaries consistent with angiolipoma. Incision into the tumors of the chest wall revealed relatively well-circumscribed, bright yellow, homogenous nodules limited to the subcutaneum. Representative histologic sections taken from 1 of the nodules were diagnostic of angiolipoma; the remainder were not sampled (Figures 2 and 3).
The autopsy was completed revealing 95% stenosis of the proximal left anterior descending coronary artery by atherosclerotic plaque. Sections of the left ventricular myocardium showed mild perivascular fibrosis. The brain was coronally sectioned disclosing a 3-cm brown, depressed region with strands of bridging tissue in the cortex of the left anterior temporal lobe. Histologic sections showed laminar disorganization with neuronal clustering and strands of fine connective tissue intertwined with glial fibers; the possibility of an in utero ischemic injury or developmental anomaly could not be excluded. The remainder of the internal examination was unremarkable. Specifically, there were no masses suspicious for neurofibroma within the major nerve trunks. No lesions associated with neurofibromatosis were noted in other organ systems (Table 1).8,9
The decedent's family was contacted to clarify the diagnosis of neurofibromatosis; unfortunately the data provided were incomplete. The diagnosis had never been documented histologically. Rather, it was assumed based on the presence of numerous subcutaneous tumors in combination with Lisch nodules. A phenotypic family tree was constructed that showed that the decedent's mother and 3 of 8 siblings (2 males, 1 female) were afflicted with similar painful subcutaneous tumors resulting in multiple excisions (Figure 4). The outside pathology reports could not be obtained, and the diagnoses cannot be definitively ascertained.
Interestingly, 1 brother also suffered from long-standing seizures refractory to therapy; however, ethanol abuse may have been a contributing factor. No Lisch nodules were noted in other family members.
The history of multiple subcutaneous tumors in several family members taken in combination with documented angiolipomas in the index case strongly suggests familial angiolipomatosis. The phenotypes noted in other family members are most consistent with an autosomal dominant pattern of inheritance; however, a dominant sex-linked pattern cannot be excluded. Most cases of familial angiolipomatosis are inherited in an autosomal recessive pattern.
Angiolipomatosis was first described in 1912.3 Since then, several cases have been described of familial angiolipomatosis.5–7 In 3 of these series, an autosomal dominant pattern of inheritance has been determined.5,7 In 1 of these reports, angiolipomatosis was clinically confused with neurofibromatosis and was seen in combination with a granular cell tumor.5 It was suggested that given the neural crest derivation of this tumor, a link might exist between neurofibromatosis type 1 and angiolipomatosis.5 In the case described herein, the presence of Lisch nodules in combination with angiolipomata also raises this possibility. Further evidence supporting a relationship between fatty tumors and neurofibromatosis type 1 may be seen in cases of juxtamedullary spinal lipomas and mesenteric lipomas in patients with neurofibromatosis type 1.10,11 Of course, the coexistence of lesions in all of these cases may also be ascribed to random chance. In future cases, it is recommended that fresh tissue be obtained to screen for mutations in the NF tumor suppressor gene on chromosome 17q11.2.9 Unfortunately, in this case the decedent's surviving family members were not willing to participate in genetic screening. Other rare syndromes associated with multiple lipomas to be included in the differential include Bannayan-Zonana syndrome,12,13 Cowden syndrome,14 Fröhlich syndrome,15 and the Proteus syndrome16 (Table 2).
Although the lesions noted on the irides were consistent with Lisch nodules, this was not confirmed microscopically. Lisch nodules (pigmented hamartomas of the iris) consist of aggregates of ovoid to round cells that form dome-shaped papules on the anterior surface of the iris. These cells are immunoreactive with S100 and vimentin, suggesting neuroectodermal origin.17,18 Lisch nodules must be distinguished from tapioca melanoma of the iris, nodular nevi, and other ocular manifestations of neurofibromatosis, including corneal hamartomas.19,20 Alteration in pigmentation of the iris can follow ocular trauma; however, there was no history of remote injury to the eye in this case.
It is important to distinguish neurofibromatosis type 1 from angiolipomatosis at autopsy in order to provide accurate information to surviving family members. Whereas neurofibromatosis type 1 is associated with significant morbidity and a myriad of neoplasms, both benign and malignant, angiolipomatosis is a benign condition with no established malignant potential.