Atypical fibroxanthoma with dermal amyloid deposit.
Atypical fibroxanthoma (AFX) is a cell neoplasm occurring mainly (or only, according to some criteria) on sunexposed skin. It can be spindle, epithelioid, or (the most common) a mixture of spindle and epithelioid. From a morphologic point of view, several secondary changes have been described as being associated with AFX, such as keloidal areas, myxoid or chondroid changes, osteoclast-like giant cells, sclerosis, fibrosis, pigmentation, hyalinization, or hemorrhagic areas (1-3). However, we have not found any reported cases of dermal amyloid deposits related to AFX. Such deposits are very common in other cutaneous tumors and they have often been published in cases of basal cell carcinoma (BCC) (4-10).
This paper reports a case of AFX with amyloid deposits inter-mingled with the periphery of the tumor.
The patient, a 77-year-old male, had a 4 cm ulcerated tumor on the forehead that had rapidly grown in the last few months. The lesion was excised and sent to the pathology department for examination.
The lesion was fixed in 10% formaldehyde and embedded in paraffin using conventional methods. After that, 4 [micro]m-thick sections were obtained and routine hematoxylin eosin stained slides were made.
The lesion was also immunostained for the antibodies shown in Table 1. Staining was performed with EnVision/DAB (Dako, Glostrup, Denmark).
Table 1 | Antibodies used in the immunohistochemical study. CK - cytokeratin, MMAH - monoclonal mouse antihuman, EMA - epithelial membrane antigen SMA - smooth muscle actin. Antibody Manufacturer Type Clone Isotype Code CK7 Dako MMAH OV-TL IgG1, M7018 12/30 kappa Desmin Dako MMAH D33 IgG1, M0760 kappa EMA Dako MMAH E29 IgG2a, M0613 kappa Melan-A Dako MMAH A103 IgG1, M7196 kappa S100 Dako Polyclonal - - Z0311 rabbit anti-S100 HMB-45 Dako MMAH HMB-45 - IR05 SMA Dako MMAH 1A4 IgG2a, M0851 kappa Caldesmon Dako MMAH h-CD IgG1, M3557 kappa CD34 Dako MMAH QBEnd IgG1, M7165 10 kappa CD31 Dako MMAH JC70A IgG1, M0823 kappa Factor Dako Polyclonal - - IR527 VIII rabbit anti-human CK20 Dako MMAH Ks20.8 IgG2a, M7019 kappa CK Dako MMAH AE1/AE3 IgG1, M3515 AE1/AE3 kappa CK high Dako MMAH 34PE12 IgG1, M0630 molecular kappa weight CAM5.2 Becton - - - - Dickinson CK 5/6 Dako MMAH D5/16 IgG1, M7237 B4 kappa CK 7 Dako MMAH OV-TL IgG1, M7018 12/30 kappa CK 8 Dako MMAH 35PH11 - N1560 CD 10 Dako MMAH 56C6 IgG1 M7308 CD 68 Dako MMAH PG-M1 IgG3, M0876 kappa CD 117 Dako Polyclonal - - A4502 rabbit anti-human
The tumor showed a classic atypical fibroxanthoma made of a diffuse spindle cell dermal growth with marked cellular atypias, giant cells, and atypical mitoses (Fig. 1). In some areas, the tumor was ulcerated, although no connection between the tumor and the epidermis was observed (Fig. 2, top left).
The tumor failed to immunostain with antibodies for cytokeratin (CK)7, desmin, epithelial membrane antigen (EMA), Melan-A, S-100 protein, HMB-45, smooth muscle actin, caldesmon, CD34, CD31, Factor VIII, CK20, CKs AE1/AE3, CK 34betaE12, CAM 5.2, CK 5.6, CK 7, and CK8. It expressed CD10 and also CD68, although focally. CD117 demonstrated abundant mast cells in the tumor.
In the periphery of the lesion, a moderate inflammatory chronic lymphoplasmacytic infiltrate was found. Amyloid deposits were also found in the periphery of the tumor, intermingling with the spindle cell proliferation (Fig. 2, top right). Such deposits were positive with Congo red staining (Fig. 2, left; but negative after permanganate treatment). The deposit was also immunostained with antibodies against CKs (AE1/AE3 and CK5/6; Fig. 2, right). It did not stain with antiamyloid A, or with antibodies against either kappa light or lambda light chains. Therefore, the amyloid deposit was keratinic in nature.
Many secondary changes have been described in atypical fibroxanthoma, such as keloidal areas, myxoid or chondroid changes, osteoclast-like giant cells, sclerosis, fibrosis, pigmentation, hyalinization, or hemorrhagic areas (1-3, 11-19). We have not found any published case of this type of amyloid in an atypical fibroxan-thoma. However, the well-known polemic on the nature of atypical fibroxanthoma as a spindle-squamous cell carcinoma (SCC) should be remembered (20) because cases of cutaneous amyloidosis related to common SCC have been reported (5).
Amyloid deposits have been related to other types of cutaneous tumors, including basal cell carcinoma (4-10), syringocystadeno-ma papilliferum (21), or trichoepithelioma (22). Other cutaneous lesions also related to amyloid deposits are linear verrucous epidermal nevus (23), melanocytic nevus (23, 24), seborrheic kerato-sis (5), actinic keratosis (6), or Bowen's disease (25).
In our case we wondered whether the amyloid could be related to the tumor or whether it might perhaps be a coincidental finding (i.e., an atypical fibroxanthoma developing on skin already affected by amyloidosis). Arguing against this latter hypothesis, we found the deposits only in the periphery of the tumor, and not in the most peripheral areas of the biopsy, which showed non-tumor skin. In addition, the patient did not present any other lesions clinically suggestive of cutaneous amyloidosis.
As shown in the figures for this case, the deposit was close to an area with a marked peritumoral lymphoplasmacytic inflammatory infiltrate. Such an infiltrate could be responsible for the epidermal damage that would have caused the amyloid deposit in a pathogenetic sequence similar to the one observed in lichen planus, for instance (26).
Amyloid deposits should be distinguished from other changes that have been occasionally associated with AFX, such as keloidal collagen (2), or from acellular hyalinization (1). The latter has been described as being associated with lymphoplasmacytic inflammatory infiltrate, as a regressive phenomenon in AFX (3). Both changes can show eosinophilic hyaline areas that mimic amyloid in routine studies. However, such areas will not stain with amyloid techniques (such as Congo red) or with antibodies for CKs. It should be remembered that recently Cassarino reported a case of aberrant expression of CK5/6 in atypical fibrous histiocytoma (27). However, in this case, CK5/6 stained the tumor cells and not any type of hyaline deposit. It is also debatable whether such cases corresponded to AFX or to spindle-cell carcinomas.
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Angel Fernandez-Flores (1)s
(1) Department of Pathology. Hospital El Bierzo. Medicos sin Fronteras 7, 24411 Ponferrada, Spain. Corresponding author: email@example.com
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|Publication:||Acta Dermatovenerologica Alpina, Pannonica et Adriatica|
|Article Type:||Clinical report|
|Date:||Jan 1, 2012|
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