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On-line version ISSN 1806-4841
An. Bras. Dermatol. vol.79 no.4 Rio de Janeiro July/Aug. 2004
Digital clubbing as the initial diagnosis of bronchogenic cancer*
Alex Gonçalves MacedoI; Valeria Cristiane FusariII; José Roberto Paes de AlmeidaIII; Sandra Lopes Mattos e DinatoIV; Ney RomitiV
IMaster's Degree in Pneumology, Escola
Paulista de Medicina, Unifesp; Assistant Professor, Clinical Medicine Section,
Pneumology Department, Unilus
IIMD, Dermatology of Guilherme Alvaro Hospital, Unilus
IIIProfessor specialized in Dermatology, Master's Degree candidate, Unilus
IVProfessor, Ph.D. in Dermatology, FMUSP. Head of the Clinical Medicine Department, Unilus
VProfessor, lecturer in Dermatology, Head of the Dermatology Service, Unilus
The authors describe a case of digital clubbing, which led to a diagnosis of bronchogenic cancer in an asymptomatic patient. Based on a review of the literature, we discuss its physiopathological aspects, associations with systemic conditions and recent methods for early diagnosis of digital clubbing. We emphasize the disease's importance in light of its association with several other diseases, including bronchogenic cancer.
Key words: carcinoma, bronchogenic; osteoarthropathy, secondary hypertrophic.
Digital clubbing was first described some 2,400 years ago by Hippocrates1,2 as digital hippocratism. It was associated with a disabling lung disease, most likely pulmonary emphysema.3 Based on this presentation, the disease has been associated with several other of similar type, including chronic bronchitis, hepatic cirrhosis, congenital cyanotic cardiopathy, malignant lung cancer, inflammatory intestinal diseases, among others that may also be of congenital origin.1 It is characterized by an increase in diameter of the distal phalanges and alterations to the fingernails. It is classified into five phases: Phase I - increase and fluctuation of the ungual bed; Phase II - loss of the natural 15° angle between the nail and cuticle; Phase III - heightened convexity of the ungual bed; Phase IV - clubbed appearance of the digital extremity; Phase V - increase of the extremity, with thickening of the distal phalange and longitudinal striations on the fingernail.1,2 In relation to bronchogenic cancer, the bones are not usually altered in digital clubbing, except when pulmonary hypertrophic osteoarthropathy is present, which is the most common of paraneoplasic syndromes in lung tumors.3,4 However, it seldom appears as the initial manifestation of the aforementioned neoplasia.
The aim of this study is to illustrate the occurrence of digital clubbing as a patient's main complaint, which subsequently led to a diagnosis of malignant pulmonary neoplasia in an adult, male patient.
A 42-year-old married male patient shopkeeper sought medical assistance with a condition of increased finger volume which was noticed by the patient's wife, and later by himself, about two months ago. He also referred to changes in the shape of his fingernails during this period. The patient denied having had other symptoms or signs, including coughing, weight loss and hemoptoic expectoration.
The physical examination showed BEG and Phase V digital clubbing in the hands (Figure 1).
Patient's social habits: social consumer of two beers per weekend. Smoker, 40 years/pack (equivalent to two packs per day for 20 years).
Family background: father died of lung cancer and brother operated for neoplasia of the larynx.
The following tests were solicited at first and showed:
- Hemogram, biochemistry, ECG, lipidogram and
urine I: normal
- TGO, TGP, total bilirubins and Fr., alkaline phosphate and GammaGT: normal;
- Hand x-ray: normal;
- Thorax x-ray: opacification in the right spiculated para-hilar region, with neoplasic characteristics (Figure 2);
With these alterations, the patient was then sent from Dermatology to Pneumology, where the diagnostic investigation proceeded. The following tests were solicited:
- Computerized tomography of the thorax: on the
right inferior lobe there was a mass with neoplasic characteristics, though
no presence of ganglions mediastinum (Figure 3);
- Bronchoscopy: did not show any endobronchial lesions. Bronchial washing, brushing and transbronchial biopsy in the right lower lobe were negative for neoplasic cells. The procedure was repeated twice, with no definitive diagnosis.
In virtue of the patient's clinical and radiological characteristics, videothorascopy with a biopsy for freezing was the method adopted, and showed a polymitotic pathology. Thoracotomy was performed with a lower right lobectomy during the same procedure. The anatomopathologic study of the piece displayed large cell undifferentiated carcinoma.
Progression: the patient's condition remained stable during the post-operatory phase. One month later, he showed signs of pain in the posterior costal region, which progressed to paraplegia. The tests showed bone metastases in the spinal column and ribs. Despite decompressive surgery and radiotherapy, the disease progressed into hepatic metastases, which led to the patient's death in two months.
For years, paraneoplasic syndromes have been studied in an attempt to understand their physiopathology, incidence and relation with various neoplasias. Yet there have been few advances in their pathogenesis, which is still not known. Vasodilation of the veins at the fingertips is believed to occur, which increases the hydrostatic pressure in the capillaries. This in turn promotes movement of fluid inside of the interstice, and results in swelling of the soft-tissue parts.5,6
An association with paraneoplasia has been reported with increased amounts of ACTH, i.e. a platelet-activating factor as well as for a variety of other mediators, and with Cushing's syndrome.7,8 In the latest publications, the presence of a hepatocytic-growth hormone has been described in patients with clubbing in association with hepatic cirrhosis, hepatocarcinoma and pulmonary adenocarcinoma.9,10
The diagnosis has undergone modifications during recent years following attempts of creating a clinical classification that would define it. When suspected clinical suspicion, one may choose to proceed to an assessment of the ratio of depth between the distal phalanges and interdigital joints, and the ratio of these two depths to a normal less-than-one ratio. In practice, one measures the distance between the distal phalange extremities and interphalangeal joints from front to back, so as to determine the ratio (bone measurement vs. joint measurement < 1, normal) (Figure 4 A).3,11-14 This clinical scale is useful in the initial phases of the disease, but in the advanced phase the diagnosis by clinical examination is relatively easy, as in this patient's case who presented with Phase V. In addition to the clinical assesment, one may use capillaroscopy, simple X-ray of the fingers, simple computerized tomography or with positron emission. These might define disease patterns or have no clinical utility at all.11,12,15 Another means of assessing the presence of clubbing is by measuring finger diameter, with no graduated scales. The normal distance between A-B is always greater than the distance between C-D (Figure 4 B).
The association with digital alterations occurs in roughly 12% of pulmonary neoplasias. It is more common in women than men, which contrasts with the case presented in this paper.
It is the most common paraneoplastic syndrome of bronchogenic tumors. It may be associated with other syndromes. The association of more than two paraneoplasias is extremely rare. In the latter, inappropriate antidiuretic hormone syndrome, Cushing's syndrome and Eaton-Lambert's syndrome are the most common.
Among the histological types, adenocarcinoma is most frequently associated with it, followed by undifferentiated large-cell carcinoma (which was found in the patient presented herein), epidermoid carcinoma and small-cell carcinoma.1,16,17,18
The appearance of digital clubbing with an initial manifestation of bronchogenic neoplasia is rare, because its formation often seems to depend on some substances being produced by the tumor itself. The earliest symptom of lung tumor is weight loss, which oddly did not occur with this patient. Weight loss may be accompanied by coughing, though the patient here did not seem duly concerned about his coughing as he associated it with his smoking habit.
There was no description found in the literature of digital clubbing as being the first motive for medical consultation in which the final diagnosis was pulmonary neoplasia. The authors believe this to occur quite seldom, given that even the presence of clubbing itself as a paraneoplastic syndrome, in spite of its greater frequency, shows low incidence. It is also believed that the use of randomized methods for research on a diagnosis of digital clubbing in the initial phase might increase its incidence, especially in patients with a relevant family history.
Upon reviewing the bibliography as prompted by the presence of this unusual case, the authors could observe that the presence of digital clubbing as the initial manifestation of pulmonary neoplasia is extremely rare. Its physiopathology remains undefined and its diagnosis still raises several doubts. Some methods tending to reduce the subjective aspect of clinical diagnoses, especially in the early phase, have been proposed in this paper. The authors believe that active research on patients with a potential risk for developing pulmonary neoplasias might reveal a greater incidence of this paraneoplasia as the condition's initial manifestation. Moreover, it is worth emphasizing the importance of dermatological examinations for elucidating internal diseases.
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Received on December 18, 2001.
Approved by the Consultive Council and accepted for publication on September 10, 2003.
* Work done at Dermatology Service, Unilus.