|Ahead of print publication
Diagnostic dilemma of a thumb swelling: An unpropitious turn of events
Seetharama B Rao1, Pooja K Suresh2, Merwyn Fernandes3, Laxman G G Prabhu4, Saraswathy Sreeram2, Rajendra Annappa1
1 Department of Orthopedics, Kasturba Medical College, Mangalore, Manipal Academy of Higher Education, Manipal, Karnataka, India
2 Department of Pathology, Kasturba Medical College, Mangalore, Manipal Academy of Higher Education, Manipal, Karnataka, India
3 Department of Radiodiagnosis, Kasturba Medical College, Mangalore, Manipal Academy of Higher Education, Manipal, Karnataka, India
4 Department of Urology, Kasturba Medical College, Mangalore, Manipal Academy of Higher Education, Manipal, Karnataka, India
|Date of Submission||25-Sep-2018|
|Date of Acceptance||04-Jan-2019|
|Date of Web Publication||29-Jan-2020|
Pooja K Suresh,
Department of Pathology, Kasturba Medical College, Mangalore, Manipal Academy of Higher Education, Manipal, Karnataka
Source of Support: None, Conflict of Interest: None
Benign and malignant bone tumors arise in small bones of the hands and feet. Nevertheless, secondary deposits at these sites are extremely rare. We report a peculiar case of an adult man who presented with thumb swelling, which was later discovered to be a metastasis from renal cell carcinoma. Such cases have a sinister prognosis with a survival rate of 6–12 months from the time of diagnosis. We intend to discuss the diagnostic dilemma and treatment of acrometastases.
Keywords: Acrometastases, renal cell carcinoma, thumb
| > Introduction|| |
Thumb swelling can be caused by a variety of causes ranging from inflammation to neoplasia. It is a rare site for benign and malignant bone and soft-tissue tumors. The common lesions involving the thumb are paronychia, osteomyelitis, rheumatoid arthritis, gout, fractures, and tenosynovitis. Glomus tumors are known to present in fingertips as painful lesions. Metastases to digits are characteristically seen as a late manifestation of some of the malignancies. However, few patients may have acrometastases as their first sign of malignancy.,, We report a case of an adult man with a thumb lesion, which was the first presentation of renal cell carcinoma (RCC).
| > Case Report|| |
A 55-year-old man presented to the orthopedics outpatient department (OPD) with swelling and pain of the left thumb for the past 2 weeks. The lesion was initially small with a gradual increase in size and was located around the nail. The pain was continuous, nonradiating, aggravated by movements and relieved with rest. There was no history of trauma or any constitutional symptoms. He had neither significant history nor comorbidities. He had visited a local hospital wherein an attempt was made to aspirate/incise the swelling under local anesthesia. As the swelling started to bleed, he was referred to our tertiary care center for further management.
General physical examination did not divulge any abnormalities. Local examination of the thumb revealed a circumferential hard swelling measuring about 2 cm × 1 cm at the base of an unhealthy friable nail, with signs of acute inflammation. There was minimal local tenderness [Figure 1]a, [Figure 1]b, [Figure 1]c. There was no local lymphadenopathy. The hand had no neurovascular deficit. A full and pain-free range of movement of the wrist and fingers was demonstrated.
|Figure 1: (a-c) Clinical picture of the thumb swelling. Plain radiography (d), computed tomographic scan (e and f), and magnetic resonance images (g) showing the lytic lesion in the distal phalanx|
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His routine blood tests were normal including an erythrocyte sedimentation rate of 9 mm/h. The plain radiograph showed a large lytic lesion involving the distal phalanx of the thumb with soft-tissue swelling [Figure 1]d. Computed tomography (CT) and magnetic resonance imaging also showed a soft-tissue mass with lytic bone lesion, suggestive of a glomus tumor or metastasis [Figure 1]e, [Figure 1]f, [Figure 1]g.
An open biopsy was performed under local anesthesia as an OPD procedure, and the patient was discharged after a day with advice to return for review after 15 days. Paraffin-embedded and H and E-stained slides of the biopsy tissue showed multiple bits of tumor composed of clusters of clear cells separated by delicate fibrovascular septae. The cells had moderate-to-abundant clear cytoplasm, distinct cytoplasmic membranes, and vesicular nuclei with mild-to-moderate pleomorphism. Occasional mitosis was noted. The fibrous septa showed sprinkling of mature lymphocytes. There was absence of normal adjacent soft tissue [Figure 2]a, [Figure 2]b, [Figure 2]c. Periodic acid–Schiff (PAS) stain highlighted the presence of glycogen in the cytoplasm of clear cells [Figure 2]d. Based on these findings, a differential diagnosis of clear cell carcinoma metastasis and clear cell sarcoma was given as there was no history of significant abdominal mass or any related complaints. Immunohistochemistry (IHC) showed negative staining for HMB45 and scattered positivity for S100, ruling out the possibility of clear cell sarcoma. BCl2 and CD99 were negative, thereby excluding the diagnosis of synovial sarcoma. In view of the presence of clear cells and lymphocytic sprinkling over the fibrovascular septae, seminoma was suggested as a differential; however, negativity for CD117 eliminated the diagnosis. The genital examination was also unremarkable. CD10 was done to prove metastasis from RCC while calretinin and synaptophysin were done to evince adrenocortical carcinoma. All the above markers were, however, negative [Figure 2]e and [Figure 2]f. Nevertheless, based on the morphology, a strong suspicion of metastasis from RCC was suspected and imaging studies were suggested as further workup.
|Figure 2: (a-c) Histopathology of the thumb lesion showed tumor tissue composed of clusters of clear cells separated by delicate fibrovascular septae. The fibrous septae showed sprinkling of mature lymphocytes. (a) The cells had moderate-to-abundant clear cytoplasm, distinct cytoplasmic membranes, and vesicular nuclei with mild-to-moderate pleomorphism. (d) Periodic acid–Schiff stain highlighting the presence of glycogen in the cytoplasm of clear cells. Immunohistochemistry showed scattered positivity for S100 (e) and negative staining for CD10 (f)|
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The patient came back for review on day 16 and was evaluated with radiological imaging. Abdominal ultrasound scan detected a lesion involving the upper pole of left kidney suggestive of RCC. Chest X-ray was normal. However, contrast-enhanced CT chest showed secondary deposits in both lungs. An isotope bone scan showed hot spots in the distal phalanx of thumb, carpal bones, and distal radius of the affected upper limb (T4N0M1-stage IV).
As part of a multidisciplinary approach, an urologist and a medical oncologist were consulted. Accordingly, the patient underwent radical nephrectomy of the left kidney which showed features of clear cell renal carcinoma similar to thumb lesion [Figure 3]a, [Figure 3]b, [Figure 3]c, [Figure 3]d. As a part of orthopedic treatment, the tumor had metastasized to bones around the wrist; limb salvage surgery could not be offered to this patient. Palliative radiotherapy was instituted for local control of the thumb lesion. Within 15 days following the surgical procedure, the patient developed seizures. Radio-isotope scan of the brain revealed a lesion in the right frontoparietal lobe, suggestive of metastasis. A neurologist treated the patient symptomatically. As the patient could not afford further treatment, his relatives requested for discharge with the intention of being followed up in a cancer center near his hometown. The patient was, subsequently, lost to follow-up.
|Figure 3:(a) Gross image of the excised kidney with a well-circumscribed yellow tumor in the lower pole. (b-d) Histopathology showed clear cell carcinoma with morphology similar to the thumb lesion|
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| > Discussion|| |
The incidence of acrometastases is low and accounts for 0.1% of all bone metastases.,,, They can simulate certain inflammatory lesions or benign tumors, thereby leading to misdiagnosis and improper treatment. British surgeon Handley first described the rare phenomenon of acrometastasis to the hand while reporting breast carcinoma with multiple metacarpal metastases. It is generally accepted that acrometastases are difficult to diagnose. They are often confused with paronychia, osteomyelitis, rheumatoid arthritis, gout, fractures, tenosynovitis, and other diseases. Secondaries in the hands and feet occur very rarely. Only 221 such cases have been reported in literature until 2014. A painful finger or thumb may be the first sign of malignancy, congruent with our case. Metastasis in the hand arises mainly from lung (34%), gastrointestinal tract (25%), kidney (10%), and breast (5%).,
Acrometastasis is known to occur in the vertebral bodies due to their rich vascular supply and extremities are unwanted sites of metastasis, owing to their poor vascular supply. The precise mechanism of acrometastasis is poorly understood. It is accepted that tumor cells disseminate to acral regions through vascular network rather than lymphatics. This explains the high prevalence of lung cancer metastases because they have direct access to systemic circulation through left atrium and ventricle. Other visceral tumor emboli cannot reach the systemic arteries directly because they have to pass the lungs and liver, which makes it unconventional for them to present as acrometastasis. The most commonly involved bones are the terminal phalanges in the hand, followed by metacarpals and proximal phalanges. The radiographs of the hand often demonstrate lytic lesions.
RCC accounts for 2%–3% of malignant adult tumors. Ninety percent of cases of RCC metastases are osteolytic. Histomorphology of clear cell RCC is quite distinct showing clusters of tumor cells separated by delicate fibrovascular cores. The tumor cells have clear cytoplasm and central vesicular nucleus with distinct nucleolus. However, a close differential for this morphology is adrenocortical carcinoma. They too are known to metastasize to rare sites. The metastasis from these two lesions can be differentiated by IHC. RCC shows strong positivity for CD10 and RCC antigen, while adrenocortical tumors are positive for calretinin, chromogranin, and synaptophysin. However, in our case, the IHC was negative for CD10, calretinin, and chromogranin, compounding the diagnostic predicament. A peculiar finding in our case was sprinkling of lymphocytes over the septae, which is a feature seen in seminoma and other germ cell tumors. Although there was no testicular mass on palpation, CD117 IHC was done in our case, which turned out to be negative.
As our case did not have any other symptoms, a diagnosis of clear cell sarcoma of the thumb was considered. Even though it is a rare site of occurrence, the presence of clear cells and PAS positivity in the cytoplasm prompted us to consider it as a differential. The IHC markers, which help in the diagnosis of clear cell sarcoma, are HMB45 and S100. Both these markers were negative in our case precluding its possibility.
Morphology forms the crux of pathological diagnosis. IHC is only an ancillary tool for confirming and excluding the histological differentials. There are multiple markers for the same lesion, which can be differentially expressed in various tumors. Hence, each case is unique and each tumor can express in ways manifold, unfailingly baffling the diagnostician each time.
Acrometastasis denotes a poor prognosis with a survival rate of approximately 1 year with therapy. Amputation, radiotherapy, curettage, cementation, chemotherapy, and wide excision are the forms of treatment used most often. Proximal and thumb lesions are best managed conservatively with radiation providing immediate pain relief while maintaining normal function. The survival rate is approximately 6–12 months.,
Acrometastasis by itself is infrequent; it being the initial presentation of an internal malignancy is seldom seen. A range of lesions, etiology varying from inflammatory to neoplastic, can cause thumb swelling. Diagnosis of metastasis from unknown site requires a merger of clinical findings, radiological evaluation, and histomorphology with a panel of IHC markers. Usually, these patients will have multiple metastases and hence grim prognosis. Local excision will only help in relieving the symptoms although amputation and disarticulation are considered better for clearance of tumor. Management of these patients is a multidisciplinary process.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has his consent for his images and other clinical information to be reported in the journal. The patient understands that his name and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
We would like to acknowledge the oncologist and radiotherapist of this case.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3]