INTRODUCTION
Inflammatory, infective and neoplastic lesions can present as lumps and bumps on the hand. Owing to the superficial location, lesions affecting the hand gain immediate patient attention as they are easily visible and palpable and present as lumps and bumps on the hand. These lumps and bumps can be divided into tumour-like lesions and tumours; the latter can be further subdivided into benign and neoplastic.[1] Both bone and soft-tissue tumours can affect the hand. Around 15% of all soft-tissue tumours can involve the hand.[2] Although all lesions which occur elsewhere in the body can affect the hand as well, certain lesions are more common and specific for the hand.
Even though lesions of the hand are very common, the literature available on the histopathology of these lesions is limited. We present the histopathological spectrum of all the lumps of the hand along with their demographic details. The present study aimed to assess the histopathological features of all the biopsies of lumps of hand submitted to the department of pathology during the study period along with their clinical and demographic details.
MATERIAL AND METHODS
This was a hospital-based retrospective study of 5 years of duration done between January 2016 and December 2020. The study was conducted at a tertiary-care medical college teaching hospital in southern India after obtaining approval from the institutional ethics committee board (IEC/IRB No: GMC/IEC/109/2021 dated 8 October, 2021). Eighty cases were included in the study after incorporating all the biopsies and excision specimens of the hand, wrist and forearm lesions which were submitted for histopathological examination (HPE) to the department of pathology of our medical college during the study period. The clinical and demographic details were collected from the patient requisition forms and pathology records.
The specimens submitted were received in 10% neutral-buffered formalin and after routine processing haematoxylin and eosin (Haematoxylin and eosin) stained sections were prepared and the slides were reviewed. Immunohistochemistry (IHC) and special stains were performed wherever necessary.
Statistical analysis
Descriptive statistics are reported as frequencies and percentages for categorical variables, and the mean for continuous variables. Statistical analysis was done using Microsoft Excel 2016 (Microsoft Corporation, Redmond, USA).
RESULTS
There were 80 cases during the study period, with the wide age range of <10 years to >80 years. There were 41 (51.3%) females. Right-sided lesions were 42 (52.5%) and left side were 38 (47.5%) cases. Based on the location, the forearm was more frequently involved, followed by the wrist and middle finger; lesions on the forearm were 20 (25%), wrist were 14 (17.5%), palm were 5 (6.25%), dorsum were 3 (3.75%), thumb were 2 (2.5%), index finger were 8 (10%), middle finger were 12 (15%), ring finger were 8 and little finger were 3 (3.75%). The relative distribution of lesions based on the location is shown in Table 1.
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Table 1: Relative distribution of various histopathological category of lesions based on their anatomical location
On HPE, the most frequent lesions identified were ganglion cysts accounting for 13 cases, followed by giant cell tumour (GCT) of tendon sheath accounting for 11 cases (male:female ratio = 5:6) and is also the most frequent neoplastic lesion. Neoplastic lesions were more common than non-neoplastic lesions, out of total 80 cases, 25 (31.3%) were non-neoplastic and 55 (68.8%) were neoplastic. Amongst non-neoplastic lesions, the most common lesion (13/25; 52%) was ganglion cyst (Figure 1a), which was also the most common lesion overall (13/80), followed by pyogenic granuloma (3/25), Two cases (2/25) each of epidermoid cyst, pigmented seborrheic keratosis and fungal granuloma. The septate branching hyphal forms of fungus were highlighted on special stain with Gomori’s methenamine silver (Figure 2a). There were one case each of cutaneous horn, molluscum contagiosum and granulomatous inflammation.
Figure 1: Photomicrograph showing ganglion cyst comprising fibrocollagenous cyst (inset) devoid of lining (Haematoxylin and eosin, ×100) (a). Photomicrograph showing giant cell tumour of tendon sheath comprising scattered osteoclastic giant cells admixed with mononuclear histiocytoid cells (Haematoxylin and eosin, ×100) (b). Photomicrograph showing pilomatrixoma comprising cyst lined by basaloid cells in transition to shadow cells with central oeosinophilic keratin material (Haematoxylin and eosin, ×100) (c). Photomicrograph showing enchondroma comprising lobules of calcification with focal calcification (Haematoxylin and eosin, ×100) (d). Photomicrograph showing epithelioid sarcoma compromising nodules of epithelioid cells with eosinophilic cytoplasm and vesicular nuclei and prominent nucleoli (Haematoxylin and eosin, ×40) (e). Photo micrograph showing synovial sarcoma comprising sheets of uniform ovoid cells with pale nuclei and open chromatin (Haematoxylin and eosin, ×40) (f)
Figure 2: Photomicrograph showing septate branching hyphae in case of fungal granuloma (Gomori’s methenamine silver, ×400) (a). Photomicrograph of synovial sarcoma showing immunoreactivity for CD99 (×400) (b). Photomicrograph of malignant peripheral nerve sheath tumour showing immunoreactivity for S100 (×400) (c). CD99 = Cluster of differentiation 99; S100 = Proteins with solubility in a 100%-saturated solution with ammonium sulphate at neutral pH
Amongst neoplastic lesions, mesenchymal lesions were 49 and epithelial lesions were 6. Of the mesenchymal lesions, 42 (85.7%) were benign, 1 was intermediate grade and 6 were malignant. Of the 49 mesenchymal lesions, 48 (97.1%) were soft-tissue origin and only one case was of bony origin which was enchondroma (Figure 1d). The most common benign neoplasm was GCT of tendon sheath (Figure 1b) (11/49; 22.4%), which was also the most common neoplasm overall, followed by, in decreasing order of frequency, lipomas and nerve sheath tumours (9 each), arteriovenous malformations/haemangiomas (5/49), fibromas (2/49) and one case each of myolipoma, fibrolipoma, benign fibrous histiocytoma, calcifying aponeurotic fibroma and benign spindle cell tumour (which could not be further subtyped on available tissue). Intermediate-grade tumour was only one case of palmar fibromatosis, which is only locally aggressive. Of the malignant mesenchymal neoplasms (6 cases), the most common neoplasm was synovial sarcoma (Figure 1f) accounting for 3 cases, where the diagnosis was confirmed on IHC with cluster of differentiation 99 (CD99) (Figure 2b). Of these three cases of synovial sarcoma, one case was a secondary deposit from synovial sarcoma of foot-operated 4 years back. In addition, there was one case each of epithelioid sarcoma (Figure 1e), malignant peripheral nerve sheath tumour which was confirmed on IHC with proteins with solubility in a 100%-saturated solution with ammonium sulphate at neutral pH (S100) and high-grade spindle cell sarcoma (which could not be further subtyped on available tissue). Amongst epithelial lesions, 2 were benign and 4 were malignant lesions, of which 3 were squamous cell carcinoma and one was melanoma and the two benign lesions were skin adnexal tumours, of which one was a case of eccrine poroma and the other was pilomatrixoma (Figure 1c).
Forearm lesions were 20 (epithelial = 5 [non-neoplastic, benign = 2 each and malignant = 1] and mesenchymal = 15 [benign = 14 and malignant = 1]), of which the most frequent lesion was lipoma (6 cases), followed by nerve sheath tumours (5 cases), epidermoid cyst (2 cases) and one case each of pilomatrixoma, eccrine poroma, fibroma, fibrolipoma, myolipoma, high-grade sarcoma and squamous cell carcinoma. Size of the lesions ranged between 2 cm and 5 cm (n = 12), between 1 cm and 2 cm (n = 4), > 5 cm (n = 3), <1 cm (n=1).
Lesions of the wrist were 15 cases and all of them were either inflammatory or benign neoplasms, of which the most frequent lesion was ganglion cyst (10/15 cases) and there was one case each of fungal granuloma, arteriovenous malformation, lipoma, benign nerve sheath tumour and GCT of the tendon sheath. Lesions of palm were nine cases, of which non-neoplastic epithelial lesions were two: one case each of pigmented seborrhoeic keratosis and cutaneous horn. Mesenchymal lesions were seven, of which there were two cases each of ganglion cyst and lipoma and one case each of calcifying aponeurotic fibroma (CAF), palmar fibromatosis and epithelioid sarcoma. Lesions on the dorsum were three, which were one case each of squamous cell carcinoma, benign nerve sheath tumour and fibroma.
Lesions on the thumb were two, one case each of GCT of the tendon sheath and arteriovenous malformation/haemangioma. Lesions of the index finger were 8, of which 2 were epithelial, one was non-neoplastic epithelial tumour, which was pigmented seborrhoeic keratosis another was malignant tumour (malignant melanoma). The remaining 6 were benign mesenchymal tumours, of which three were GCT of the tendon sheath, two were arteriovenous malformation/haemangioma and one was benign fibrous histiocytoma.
Lesions of the middle finger were 12, of which was malignant epithelial tumour which was squamous cell carcinoma, the remaining 11 were mesenchymal; three were non-neoplastic which were two cases of pyogenic granuloma and one case of the ganglion cyst. Benign mesenchymal neoplasms were eight, of which six were GCT of the tendon sheath, one was arteriovenous malformation/haemangioma and one was a benign nerve sheath tumour.
Lesions of the ring finger were eight, of which three were infective/inflammatory which were, one case each of fungal granuloma of Aspergillus species, molluscum contagiosum and granulomatous inflammation. The remaining five were mesenchymal neoplasms, of which three were benign comprising one case each of a bone neoplasm (enchondroma), a benign spindle cell tumour, and a benign nerve sheath tumour (schwannoma) and two malignant neoplasms (synovial sarcomas). Of the two malignant neoplasms, one was primary and the diagnosis was confirmed with IHC with CD99 (Figure 2b). The second was a patient with synovial sarcoma of foot who was operated 4 years ago; IHC with CD99 was done on the primary tumour and was positive (Figure 2c).
Lesions of the little finger were three, all of them were mesenchymal, one was non-neoplastic (pyogenic granuloma) and the other two were malignant neoplasms, one case each of synovial sarcoma and malignant peripheral nerve sheath tumour. The average follow-up ranged between 0 and 5 years. There were no incidents of recurrence during the follow-up period, except one case which was a secondary deposit from synovial sarcoma foot.
DISCUSSION
Tumours and pseudotumours/tumour-like lesions can present as lumps and bumps of the hand and can involve the skin, soft tissue and bone. Ganglion cyst was the most common lesion of the hand in this study similar to that reported in the literature.[1,2] The ganglion cysts constitute 60%–70% of hand lesions;[3] however, the relative lesser incidence (13/80; 6.3%) in this study might be because all the excised lesions are not submitted for HPE as the diagnosis is already established preoperatively on fine-needle aspiration cytology and some lesions even subside after aspiration.[4] Ganglion cysts result from myxoid degeneration and cystic transformation of the tendon sheath or joint capsule. Microscopically, they are characterised by fibrocollagenous wall devoid of any lining, a feature that distinguishes it from synovial cyst which on contrary has synovial lining and communicates with the joint capsule.[5] Other non-neoplastic cysts of the hand include epidermoid cysts and fungal granulomas presenting as cystic lesions. Fungal granulomas or abscess can occur in the hand due to accidental traumatic inoculation of fungus into the subcutis.[6] Pilomatrixoma is another cystic lesion which also presents as a keratin-filled cyst similar to epidermoid cyst. The presence of basaloid cells lining the cyst with abrupt keratinisation along with shadow cells/ghost cells is the differentiating feature from the latter.[7]
GCT of tendon sheath is the most common tumour of the hand and wrist in this study similar to that reported in the literature[1] and is the second-most common lesion of the hand after ganglion cyst. Microscopically, the lesion is composed of mononuclear histiocytoid cells admixed with osteoclast-like giant cells, siderophages and inflammatory cells. The presence of mitosis and necrosis does not seem to affect the prognosis. The diagnosis is quite straightforward histologically though sometimes predominance of siderophages may arise a differential diagnosis of other pigmented lesions like melanoma. A simple cytochemical stain for iron-like Perl’s stain will be positive in GCT which would help in differentiation. In addition, immunohistochemical stains like clusterin[8] (positive in mononuclear cells), desmin (focal/patchy positive in mononuclear cells), CD 68 (positive in osteoclast-like giant cell lesion), s100, HMB 45 and melan A (latter three are positive in melanoma) can be used for confirmation. GCT of the bone will have similar morphology and can be differentiated from the former by radiological correlation as it is located in the bone. Other common benign neoplasms encountered in this study were lipoma, benign nerve sheath tumour – schwannoma, arteriovenous malformation/haemangioma and fibroma of tendon sheath (FTS). Lipoma, schwannoma and haemangioma are quite distinct from each other histologically and can be easily diagnosed under the microscope as lipoma is composed of lobules of mature adipose tissue, schwannoma is composed of spindle cells and haemangioma is composed of either lobule of capillaries or cavernous vascular channels or thickened veins. FTS is composed of bland-looking spindle cells in the collagenous background along with characteristic slit-like thin vessels which appear as clefts.[9,10] It can undergo degenerative changes such as myxoid or cystic changes, which sometimes can be confused with Antoni B areas of schwannoma. While schwannoma is the most common benign peripheral nerve sheath tumour of the hand and is of Schwann cell origin,[11,12] the presence of palisaded Schwann cells forming Verocay, bodies, along with Antoni A and B areas in schwannoma, helps in differentiating between these two entities. In addition, IHC can also be used, smooth muscle actin (SMA) is often positive in FTS and S100 is positive schwannoma. Other rarer lesions encountered in this study are one case each of myolipoma, fibrolipoma, benign fibrous histiocytoma, calcifying aponeurotic fibroma, palmar fibromatosis and benign spindle cell tumour (could not be further subtyped). Although the incidence of lesions such as lipoma, schwannoma and haemangioma is almost similar to that elsewhere in the body, certain lesions such as CAF, FTS and palmar fibromatosis are specific for the hand. CAF is composed of calcific nodules along with fibromatous areas.[13,14] Palmar fibromatosis is an intermediate-grade neoplasm with a tendency for local recurrence and has an infiltrative growth pattern comprising spindle cells. The cellularity of the lesions varies with the duration of the lesion and older lesions tend to be less cellular and more collagenous; however, these tumours will not metastasize.[15] Another rare neoplasm that is common in the hand is the glomus tumour. It occurs commonly in fingers. However, we have not come across any glomus tumour in this study.
Sarcomas of the hand are extremely rare accounting for 1% of all adult malignancies,[16] and synovial sarcoma is amongst few that occur in that location and is the most frequent sarcoma encountered in the present study. It has a specific defining translocation t(×;18) leading to fusion gene product SS18-SSX and can be monophasic or biphasic morphologically, but in the present study, all three cases were monophasic. It is characterised by uniform-looking spindle cells in fascicles focally showing haemangiopericytomatous pattern. Biphasic tumours in addition show epithelial components composed of cells in nests, cords or glands. On IHC, though not specific, the cells can be positive for CD 99 and transducin-like enhancer 1; in addition, the epithelial component will be positive for epithelial membrane antigen (EMA) and keratins. Similarly, epithelioid sarcoma is a rare malignancy of the hand accounting for <1% of all malignant soft-tissue tumours[17] and clinically mimic other benign and infective lesions of the hand. There are two types, namely, the classic/distal type and the proximal type. Distal type is more common in the hand[17] and is characterised by large, oval round or polygonal cells with abundant eosinophilic cytoplasm and vesicular nuclei and small nucleoli[17,18] and can sometimes have deceiving looks of a benign granulomatous lesion microscopically. The diagnosis can be confirmed by IHC; the neoplastic cells will be positive for vimentin and other epithelial markers such as EMA and low-molecular-weight cytokeratin and have a loss of nuclear SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1 (SMARCB1), also known as integrase interactor 1 (INI1) expression.[19] It can undergo metastasis to regional lymph nodes and lungs. The prognosis of the distal type is better than that of the proximal type. The other sarcoma encountered in this study was malignant peripheral nerve sheath tumors, which is extremely uncommon in this location with only a few reported cases in the literature[20] and are usually associated with neurofibromatosis-1. They have diverse morphology under a microscope comprising spindle cells with extensive pleomorphism. On IHC, <50% of cases are positive for S100 and most of them are P53 positive and low molecular weight protein inhibitor of cyclin dependent kinase 4 and 6 (P16INK4a) negative. Another sarcoma that occurs in the hand and should be considered under differential diagnosis includes clear cell sarcoma, also known as melanoma of soft parts. Although it is indistinguishable from malignant melanoma, morphologically, immunohistochemically and ultrastructurally,[21] it has characteristic translocation t (12; 22)(q13; q12). We did not have any case of clear cell sarcoma in this study.
Benign and malignant bone tumours of the bone with cartilaginous differentiation can occur in the hand. The common bone tumours of the hand include enchondroma, osteoid osteoma, though rare, malignancies such as osteosarcoma, chondrosarcoma and Ewing’s sarcoma have also been reported in the literature.[22] Bony cysts like aneurysmal bone cysts are also common in this location. However, lesions of bony origin in this study were very rare and there was only one case of enchondroma. This might be because of referral bias.
Common epithelial neoplasms encountered in the hand are skin adnexal tumours and squamous cell carcinomas (SCC),[2] which was also the case in this study. SCC was the most common epithelial malignancy in this study. The morphology of SCC in the hand is similar to that elsewhere in the body, nonetheless has more tendency for local recurrence and a lesser chance of distant metastasis.[23] Malignant melanoma was the other epithelial malignancy in this study. Acral lentiginous melanoma is the most common type and melanoma of the hand is considered to be distinct anatomically, genetically and clinically.[24] However, it is similar morphologically in all sites of the body and on IHC will be positive for human melanoma black 45 (HMB 45), S100 and melanocyte inducing transcription factor (MITF).
The limitations of the study are that the lesions arising from the bone were less frequent and may not be a true representation to that in the general population as our hospital was a tertiary-level medical college hospital and bony lesions might get referred to orthopaedic centres. In conclusion, this study enumerates the lesions of the hand. Although the lesions occurring elsewhere in the body occur in the hand as well, the relative frequency of these lesions varies and some lesions are more specific to the hand like ganglion cysts and GCT of the tendon sheath. Amongst malignancies, synovial sarcoma, epithelioid sarcoma, malignant peripheral nerve sheath tumour, squamous cell carcinoma and melanoma are more common.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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