SEARCH

SEARCH BY CITATION

Abstract

  1. Top of page
  2. Abstract
  3. Drug-induced reversible lymphoid dyscrasia/drug-induced pseudolymphoma syndrome
  4. Persistent nodular arthropod bite reactions
  5. Secondary syphilis
  6. Lymphomatoid dermatitis
  7. Nodular scabies
  8. Chronic actinic dermatitis (actinic reticuloid)
  9. Fungal infections
  10. Lichen sclerosus et atrophicus
  11. Lichen striatus
  12. Lichenoid keratosis (solitary lichen planus or lichen-planus-like keratosis)
  13. Pigmented purpuric dermatitis
  14. Connective tissue disease/lupus
  15. Inflamed vitiligo
  16. Regressed malignant melanoma
  17. Conclusion
  18. References

Abstract:  Mycosis fungoides (MF) is a rare type of non-Hodgkin’s lymphoma affecting the skin. Because MF develops slowly over several years and may have a variety of clinical presentations, including itchy patches, plaques or tumors that may be confused with common benign conditions such as eczema and psoriasis, the disease presents a diagnostic challenge. The average time to diagnosis varies but is frequently as long as 3 to 6 years. Skin biopsies frequently reveal non-specific features of several dermatoses; thus, histologic evaluation of the disease is also challenging. Importantly, various significant and/or benign conditions may mimic MF histologically and result in a misdiagnosis of MF. Here we review the reported histologic mimickers of MF and discuss both similar and differentiating features of each, in order to aid in more accurate interpretation of diagnostically challenging skin biopsies. Clinicopathologic correlation is ultimately essential to make accurate diagnosis of MF and its histologic mimickers.

Mycosis fungoides (MF) represents malignant transformation of CD4+ T cells in the skin. The malignancy begins in the skin but may progress over time to involve the entire lymphoreticular system, including lymph nodes and internal organs. Differentiation of true MF from dermatologic conditions mimicking MF is important to ensure proper management of the patient’s symptoms and treatment, and to provide accurate prognostic information.

Because MF often presents as randomly distributed patches, plaques, and later tumors, it is often difficult to distinguish clinically from a myriad of common and benign conditions including eczema, psoriasis and several others. Therefore, skin biopsy has traditionally been a cornerstone of diagnosis. Skin biopsies showing features of MF must be carefully interpreted to consider the possibility of cutaneous T-cell pseudolymphoma, which may mimic MF histologically. A reported false-positive diagnosis rate of 44% and false-negative rate of 40% highlight the difficulty of correct diagnosis of MF and underscore the importance of careful review of the histologic features of MF and its many simulators.1 Here we review the histologic mimickers of MF, in order to be aware of these entities so that a wrong diagnosis of MF is not rendered.

Drug-induced reversible lymphoid dyscrasia/drug-induced pseudolymphoma syndrome

  1. Top of page
  2. Abstract
  3. Drug-induced reversible lymphoid dyscrasia/drug-induced pseudolymphoma syndrome
  4. Persistent nodular arthropod bite reactions
  5. Secondary syphilis
  6. Lymphomatoid dermatitis
  7. Nodular scabies
  8. Chronic actinic dermatitis (actinic reticuloid)
  9. Fungal infections
  10. Lichen sclerosus et atrophicus
  11. Lichen striatus
  12. Lichenoid keratosis (solitary lichen planus or lichen-planus-like keratosis)
  13. Pigmented purpuric dermatitis
  14. Connective tissue disease/lupus
  15. Inflamed vitiligo
  16. Regressed malignant melanoma
  17. Conclusion
  18. References

A pseudolymphoma syndrome characterized by generalized lymphadenopathy, hepatosplenomegaly, fever, arthralgia, eosinophilia and an erythematous eruption has been described in association with certain drugs, especially antiepileptic drugs. Reported cases have shown a band-like infiltrate with cerebriform nuclei in the dermis and possible Pautrier-like microabscesses in the epidermis, often making drug-induced pseudolymphoma histologically indistinguishable from MF.2 The diagnosis has been established by the clearing of the skin lesions upon discontinuation of the offending drug.3 Implicated drugs include phenytoin, carbamazepine, sodium valproate, gemcitabine, gold and the clonidine patch.3 Gleevec, a protein tyrosine kinase inhibitor, has been reported to have induced a perivascular infiltrate of large hyperchromatic lymphocytes with focal epidermotropism resembling MF in one patient. The 1:1 CD4:CD8 ratio of the infiltrate, however, was consistent with a reactive process and allowed for a diagnosis of drug-induced pseudolymphoma.4

Persistent nodular arthropod bite reactions

  1. Top of page
  2. Abstract
  3. Drug-induced reversible lymphoid dyscrasia/drug-induced pseudolymphoma syndrome
  4. Persistent nodular arthropod bite reactions
  5. Secondary syphilis
  6. Lymphomatoid dermatitis
  7. Nodular scabies
  8. Chronic actinic dermatitis (actinic reticuloid)
  9. Fungal infections
  10. Lichen sclerosus et atrophicus
  11. Lichen striatus
  12. Lichenoid keratosis (solitary lichen planus or lichen-planus-like keratosis)
  13. Pigmented purpuric dermatitis
  14. Connective tissue disease/lupus
  15. Inflamed vitiligo
  16. Regressed malignant melanoma
  17. Conclusion
  18. References

Persistent arthropod bite reactions have often been classified as pseudolymphomas because of the dense dermal inflammatory infiltrate with numerous lymphocytes. One case demonstrating a broad and deep dermal atypical cellular infiltrate, without epidermal changes, was initially diagnosed as a non-epidermotropic T-cell lymphoma.5 A lack of abnormalities on chest radiography, computed tomography of the abdomen and pelvis, and blood studies led to reconsideration of the diagnosis. A second interpretation was then obtained which made note of plasma cells and eosinophils in the infiltrate, patchy staining with the B-cell marker CD20 and the clinical history of a wasp sting in the location of the biopsy area 3 months prior, leading to a revised diagnosis of persistent nodular arthropod bite reaction. In considering such cases, overlying spongiosis of the epidermis, when present, also supports a diagnosis of arthropod bite rather than MF. In addition, the formation of lymphoid follicles in a persistent bite reaction, with germinal center formation and lack of clonality, have aided in the diagnosis in cases mimicking MF.6

Secondary syphilis

  1. Top of page
  2. Abstract
  3. Drug-induced reversible lymphoid dyscrasia/drug-induced pseudolymphoma syndrome
  4. Persistent nodular arthropod bite reactions
  5. Secondary syphilis
  6. Lymphomatoid dermatitis
  7. Nodular scabies
  8. Chronic actinic dermatitis (actinic reticuloid)
  9. Fungal infections
  10. Lichen sclerosus et atrophicus
  11. Lichen striatus
  12. Lichenoid keratosis (solitary lichen planus or lichen-planus-like keratosis)
  13. Pigmented purpuric dermatitis
  14. Connective tissue disease/lupus
  15. Inflamed vitiligo
  16. Regressed malignant melanoma
  17. Conclusion
  18. References

Secondary syphilis is known as the ‘great imitator’ clinically and may also fill this role histologically, as a variety of histologic patterns have been reported. The rare nodular form of secondary syphilis has been reported to have mimicked MF both clinically and histologically. In one reported case, findings of a dense infiltrate containing lymphocytes with cerebriform nuclei, single-cell epidermotropism and folliculotropism with follicular mucinosis led to an initial interpretation of atypical lymphoid infiltrate, possibly representing MF.7 Further biopsy specimens revealed numerous plasma cells and showed the infiltrate to have nearly equal proportions of B and T cells and be polyclonal in nature. This led to a suspicion of syphilis rather than MF, and a positive rapid plasma reagin test confirmed the diagnosis of secondary syphilis. As is exemplified by this case, the presence of numerous plasma cells should prompt consideration of secondary syphilis. When present, characteristic histologic features of secondary syphilis such as endarteritis, perivascular plasma cell infiltrate, inflammatory infiltrate obscuring the dermoepidermal junction and epidermal hyperplasia also raise the possibility of secondary syphilis. As is always prudent with this disease of many disguises, secondary syphilis should be considered in the differential diagnosis of lesions showing histologic features of MF.

Lymphomatoid dermatitis

  1. Top of page
  2. Abstract
  3. Drug-induced reversible lymphoid dyscrasia/drug-induced pseudolymphoma syndrome
  4. Persistent nodular arthropod bite reactions
  5. Secondary syphilis
  6. Lymphomatoid dermatitis
  7. Nodular scabies
  8. Chronic actinic dermatitis (actinic reticuloid)
  9. Fungal infections
  10. Lichen sclerosus et atrophicus
  11. Lichen striatus
  12. Lichenoid keratosis (solitary lichen planus or lichen-planus-like keratosis)
  13. Pigmented purpuric dermatitis
  14. Connective tissue disease/lupus
  15. Inflamed vitiligo
  16. Regressed malignant melanoma
  17. Conclusion
  18. References

Lymphomatoid allergic contact dermatitis with a dense, band-like lymphocytic infiltrate has been reported to mimic the similar dense and band-like infiltrate often seen in MF. In two reported cases, the dense infiltrate was initially diagnosed as consistent with MF.8,9 In each case, the correct diagnosis of allergic contact dermatitis was eventually established after positive patch reactions to allergens known to be in contact with the biopsy site were found: the first was a biopsy of hand dermatitis, with an allergy to the striker part of a matchbox, and the second was a biopsy of a left posterior thigh dermatitis, with an allergy to a rubber eraser the patient carried in his back pocket. Ackerman et al. also warned that allergic contact dermatitis could closely mimic MF, reporting several cases of spongiotic dermatitis, most often allergic contact dermatitis, with foci of atypical mononuclear cells that he cautioned could be easily misdiagnosed as Pautrier microabscesses.10

Histologically, MF does not often demonstrate the epidermal changes of spongiosis, apoptosis or acanthosis that are commonly seen in dermatitis. Therefore, the presence of significant spongiosis favors a diagnosis of dermatitis in cases mimicking MF. However, vesicular variants of MF do occur, and in cases with intraepidermal or subcorneal vesiculation, MF cannot be ruled out.11 Significant upper dermal edema should suggest an inflammatory dermatosis over a diagnosis of MF. Intraepidermal inflammatory cells may be differentiated from mycosis cells more easily if they are present in flask-shaped collections, with the mouth of the flask open at the stratum corneum.11 The presence of Langerhans cell collections also favors a reactive process. These may be identified as collections of large cells with abundant cytoplasm, pale indented nuclei and positive CD1a staining. Dermatitis often lacks the classic epidermal lymphocytic atypia seen in MF.12 Also, there is retention of pan-T-cell markers and usually no abnormal T-cell receptor (TCR) rearrangement. A positive patch test may aid in confirmation of contact dermatitis in equivocal cases.13

Nodular scabies

  1. Top of page
  2. Abstract
  3. Drug-induced reversible lymphoid dyscrasia/drug-induced pseudolymphoma syndrome
  4. Persistent nodular arthropod bite reactions
  5. Secondary syphilis
  6. Lymphomatoid dermatitis
  7. Nodular scabies
  8. Chronic actinic dermatitis (actinic reticuloid)
  9. Fungal infections
  10. Lichen sclerosus et atrophicus
  11. Lichen striatus
  12. Lichenoid keratosis (solitary lichen planus or lichen-planus-like keratosis)
  13. Pigmented purpuric dermatitis
  14. Connective tissue disease/lupus
  15. Inflamed vitiligo
  16. Regressed malignant melanoma
  17. Conclusion
  18. References

The nodular variant of scabies often displays a dense, chronic inflammatory lymphocytic infiltrate with eosinophils that has been mistaken for the dense lymphocytic infiltrate seen in MF.14 In one reported case, a predominantly T-cell infiltrate with epidermotropism and Pautrier-like microabscesses was initially felt to represent a T-cell lymphoma.15 However, a colleague noticed a mite in the epidermis of one section, confirming the diagnosis of scabies. In cases where mites are not found, clearing after scabetic therapy will establish the diagnosis; however, it should be noted that nodules may persist for months after therapy.16

Chronic actinic dermatitis (actinic reticuloid)

  1. Top of page
  2. Abstract
  3. Drug-induced reversible lymphoid dyscrasia/drug-induced pseudolymphoma syndrome
  4. Persistent nodular arthropod bite reactions
  5. Secondary syphilis
  6. Lymphomatoid dermatitis
  7. Nodular scabies
  8. Chronic actinic dermatitis (actinic reticuloid)
  9. Fungal infections
  10. Lichen sclerosus et atrophicus
  11. Lichen striatus
  12. Lichenoid keratosis (solitary lichen planus or lichen-planus-like keratosis)
  13. Pigmented purpuric dermatitis
  14. Connective tissue disease/lupus
  15. Inflamed vitiligo
  16. Regressed malignant melanoma
  17. Conclusion
  18. References

Chronic actinic dermatitis, a photoallergic dermatosis seen in older men, may mimic MF both clinically and histologically. Cases of chronic actinic dermatitis have been reported which show very little spongiosis, Pautrier-like microabscesses and possible atypical hyperchromatic cells with cerebriform nuclei, thus resembling lymphoma.17,18 Ultimately, acanthosis, papillary dermal changes similar to lichen simplex chronicus (thickened papillary dermis with vertically oriented coarse collagen bundles parallel to the rete ridges), stellate multinucleated fibroblasts and thickened and increased blood vessels aid in differentiation from CD8+ variants of MF and aid in making the correct diagnosis of actinic reticuloid. The lymphocytes are most often CD8+,19 allowing for distinction from MF, which is generally CD4+. The diagnosis may be confirmed by phototesting showing positive photosensitivity to ultraviolet (UV) A and UVB light.

Fungal infections

  1. Top of page
  2. Abstract
  3. Drug-induced reversible lymphoid dyscrasia/drug-induced pseudolymphoma syndrome
  4. Persistent nodular arthropod bite reactions
  5. Secondary syphilis
  6. Lymphomatoid dermatitis
  7. Nodular scabies
  8. Chronic actinic dermatitis (actinic reticuloid)
  9. Fungal infections
  10. Lichen sclerosus et atrophicus
  11. Lichen striatus
  12. Lichenoid keratosis (solitary lichen planus or lichen-planus-like keratosis)
  13. Pigmented purpuric dermatitis
  14. Connective tissue disease/lupus
  15. Inflamed vitiligo
  16. Regressed malignant melanoma
  17. Conclusion
  18. References

We have observed several cases of tinea and candidiasis with band-like infiltrates of lymphocytes, including atypical forms, and lymphocytic exocytosis suggestive of MF (Fig. 1A, B). However, Periodic Acid-Schiff (PAS) examination showed the presence of Candida or dermatophyte infection (Fig. 1C). This underscores the importance of performing PAS examination in all skin biopsies with inflammatory infiltrates.20 It is also interesting to point out that some MF cases have been shown to have a concomitant fungal infection.21

image

Figure 1. A case of Candida infection mimicking cutaneous T-cell lymphoma (A–C). A) A moderately dense band-like lymphocytic infiltrate with lymphocytic exocytosis (hematoxylin and eosin ×10). B) Collections of lymphocytes in the epidermis as well as some lymphocytes with atypical cerebriform nuclei. Pseudohyphae are visible in the stratum corneum (hematoxylin and eosin ×20). C) Budding yeast and pseudohyphae in the stratum corneum (PAS ×20).

Download figure to PowerPoint

Lichen sclerosus et atrophicus

  1. Top of page
  2. Abstract
  3. Drug-induced reversible lymphoid dyscrasia/drug-induced pseudolymphoma syndrome
  4. Persistent nodular arthropod bite reactions
  5. Secondary syphilis
  6. Lymphomatoid dermatitis
  7. Nodular scabies
  8. Chronic actinic dermatitis (actinic reticuloid)
  9. Fungal infections
  10. Lichen sclerosus et atrophicus
  11. Lichen striatus
  12. Lichenoid keratosis (solitary lichen planus or lichen-planus-like keratosis)
  13. Pigmented purpuric dermatitis
  14. Connective tissue disease/lupus
  15. Inflamed vitiligo
  16. Regressed malignant melanoma
  17. Conclusion
  18. References

A recent study described nine cases of lichen sclerosus presenting with histologic features of MF.22 MF was suggested because of dense band-like infiltrates with exocytosis of lymphocytes into the lower epidermis, hyperkeratosis and superficial dermal fibrosis. A monoclonal TCR gamma gene rearrangement was detected in one of the nine cases. We have observed a similar case (Fig. 2A–D), which showed a narrow band of papillary dermal homogenization, band-like lymphocytic infiltrate, basal lymphocytes and lymphocytic exocytosis suggestive of MF. However, the clinical findings and negative polymerase chain reaction studies were consistent with lichen sclerosus et atrophicus (LSA). Lichen sclerosus is most often found in the vulvar or perianal area of females as white plaques, and thus the clinical description may strongly suggest LSA over MF.

image

Figure 2. Lichen sclerosus et atrophicus mimicking cutaneous T-cell lymphoma (A–D). A) A moderately dense, band-like lichenoid lymphocytic infiltrate (hematoxylin and eosin ×20). B) Band-like lymphocytic infiltrate with marked lymphocytic exocytosis (hematoxylin and eosin ×20). C) High-power magnification of (A) shows an area of papillary dermal homogenization and basal layer lymphocytes (hematoxylin and eosin ×40). D) A narrow band of papillary dermal homogenization above the infiltrate, basal layer lymphocytes and epidermotropism (hematoxylin and eosin ×40).

Download figure to PowerPoint

Lichen striatus

  1. Top of page
  2. Abstract
  3. Drug-induced reversible lymphoid dyscrasia/drug-induced pseudolymphoma syndrome
  4. Persistent nodular arthropod bite reactions
  5. Secondary syphilis
  6. Lymphomatoid dermatitis
  7. Nodular scabies
  8. Chronic actinic dermatitis (actinic reticuloid)
  9. Fungal infections
  10. Lichen sclerosus et atrophicus
  11. Lichen striatus
  12. Lichenoid keratosis (solitary lichen planus or lichen-planus-like keratosis)
  13. Pigmented purpuric dermatitis
  14. Connective tissue disease/lupus
  15. Inflamed vitiligo
  16. Regressed malignant melanoma
  17. Conclusion
  18. References

Lichen striatus frequently exhibits several non-specific histopathologic features and general lichenoid changes, which make diagnosis of this chameleon-like disease challenging. One study of 41 cases showed 10 cases which simulated other disease closely, of which 3 of these 10 simulated MF.23 In these cases, pagetoid spread of large hyperchromatic lymphocytes and the presence of a band-like lymphocytic infiltrate simulated MF. The finding of features of lichen striatus such as collections of histiocytes within the epidermis and also the observation that the epidermotropic cells were CD8+ provided clues to the correct diagnosis of lichen striatus. We have observed a case where the diagnosis was mistaken for MF, including a band-like superficial infiltrate with epidermotropism and haloed lymphocytes in the basal layer (Fig. 3A–C). Clinicopathologic correlation was however not good for MF, and a diagnosis of lichen striatus was considered. TCR gene rearrangement was negative, and the patient is well after 3 years of follow up, without any signs of disease. Epidermal changes such as spongiosis, edema and focal parakeratosis usually permit differentiation from MF.24

image

Figure 3. Lichen striatus mimicking cutaneous T-cell lymphoma (A–C). A) A perivascular and lichenoid lymphocytic infiltrate of moderate density (hematoxylin and eosin ×10). B) Band-like lymphocytic infiltrate, papillary dermal fibrosis and epidermotropism (hematoxylin and eosin ×20). C) Band-like lymphocytic infiltrate, papillary dermal fibrosis, lymphocytic exocytosis resembling Pautrier abscess and dermal lymphoid cell infiltrate (hematoxylin and eosin ×40).

Download figure to PowerPoint

Lichenoid keratosis (solitary lichen planus or lichen-planus-like keratosis)

  1. Top of page
  2. Abstract
  3. Drug-induced reversible lymphoid dyscrasia/drug-induced pseudolymphoma syndrome
  4. Persistent nodular arthropod bite reactions
  5. Secondary syphilis
  6. Lymphomatoid dermatitis
  7. Nodular scabies
  8. Chronic actinic dermatitis (actinic reticuloid)
  9. Fungal infections
  10. Lichen sclerosus et atrophicus
  11. Lichen striatus
  12. Lichenoid keratosis (solitary lichen planus or lichen-planus-like keratosis)
  13. Pigmented purpuric dermatitis
  14. Connective tissue disease/lupus
  15. Inflamed vitiligo
  16. Regressed malignant melanoma
  17. Conclusion
  18. References

A recent retrospective study called attention to an MF-like histologic pattern of benign lichenoid keratoses, showing most frequently Pautrier microabscesses and alignment of lymphocytes along the basal layer (>90%).25 Epidermotropism was also frequently found (80%). Other features included cerebriform nuclei in lymphocytes, epidermal atrophy, larger lymphocytes in the epidermis than those in the dermis and papillary dermal fibrosis. The presence of at least one of the following features of lichenoid keratosis aided in a diagnosis of lichenoid keratosis in 87% of the cases studied: wedge-shaped hypergranulosis, necrotic keratinocytes, eosinophils, adjacent solar lentigo or seborrheic keratosis, pointed contour of the rete ridges and plasma cells.

Pigmented purpuric dermatitis

  1. Top of page
  2. Abstract
  3. Drug-induced reversible lymphoid dyscrasia/drug-induced pseudolymphoma syndrome
  4. Persistent nodular arthropod bite reactions
  5. Secondary syphilis
  6. Lymphomatoid dermatitis
  7. Nodular scabies
  8. Chronic actinic dermatitis (actinic reticuloid)
  9. Fungal infections
  10. Lichen sclerosus et atrophicus
  11. Lichen striatus
  12. Lichenoid keratosis (solitary lichen planus or lichen-planus-like keratosis)
  13. Pigmented purpuric dermatitis
  14. Connective tissue disease/lupus
  15. Inflamed vitiligo
  16. Regressed malignant melanoma
  17. Conclusion
  18. References

Twenty-nine of 56 patients with pigmented purpuric dermatitis (PPD) showed histologic patterns typical of MF, including epidermotropism, papillary dermal fibrosis, lymphocytic atypia and epidermal hyperplasia.26 We have seen similar cases with prominent papillary dermal lymphocytic infiltrate, lymphocytic exocytosis and papillary dermal fibrosis, giving the appearance of MF (Fig. 4A–D). However, extravasation of red blood cells, along with clinical findings and negative T-cell gene rearrangement was more consistent with pigmented purpura.

image

Figure 4. Pigmented purpuric dermatitis mimicking cutaneous T-cell lymphoma (A–D). A) Moderately dense, band-like lichenoid lymphocytic infiltrate (hematoxylin and eosin ×10). B) Papillary dermal fibrosis and marked lymphocytic exocytosis (hematoxylin and eosin ×20). C) Extensive lymphocytic exocytosis along with haloed lymphocytes (hematoxylin and eosin ×40). D) Numerous extravasated erythrocytes and lymphohistiocytic infiltrate and basal lymphocytes (hematoxylin and eosin ×20).

Download figure to PowerPoint

Melanophages and extravasated erythrocytes may be present in both PPD and MF. When differentiating between the two conditions, the presence of intraepidermal lymphocytes larger than dermal lymphocytes, atypical lymphocytes in the dermis and papillary dermal fibrosis support a diagnosis of MF over PPD.26,27 While cases of PPD have clinically resembled MF and vice versa, it is unlikely that clear, undisputed cases of PPD have the potential to progress to MF as has been suggested by some.1

Connective tissue disease/lupus

  1. Top of page
  2. Abstract
  3. Drug-induced reversible lymphoid dyscrasia/drug-induced pseudolymphoma syndrome
  4. Persistent nodular arthropod bite reactions
  5. Secondary syphilis
  6. Lymphomatoid dermatitis
  7. Nodular scabies
  8. Chronic actinic dermatitis (actinic reticuloid)
  9. Fungal infections
  10. Lichen sclerosus et atrophicus
  11. Lichen striatus
  12. Lichenoid keratosis (solitary lichen planus or lichen-planus-like keratosis)
  13. Pigmented purpuric dermatitis
  14. Connective tissue disease/lupus
  15. Inflamed vitiligo
  16. Regressed malignant melanoma
  17. Conclusion
  18. References

A case of chronic cutaneous lupus erythematosus displaying epidermotropism and atypical lymphocytic infiltrate initially diagnosed as MF was reported.28 Repeated biopsies, however, showed features of lupus erythematosus. A positive antinuclear antibody test and good response to hydroxychloroquine led to a diagnosis of chronic cutaneous lupus erythematosus mimicking MF. In equivocal cases, a positive lupus band test in lesional skin will establish the diagnosis of lupus erythematosus. Another study of patients with atypical lymphoid infiltrates arising in the setting of diagnosed connective tissue disease reported a pattern of infiltrates which mimicked MF because of a dense, atypical, epidermotropic or folliculotropic T-cell-rich lymphocytic infiltrate, including cells with cerebriform nuclei.29 Clinically, the lesions resembled subcutaneous lupus erythematosus (SCLE) and discord lupus erythematosus (DLE). In all cases, concomitant lymphomatoid vasculitis, a polymorphous infiltrate with numerous histiocytes, pan-T-cell marker preservation and polyclonal TCR gene rearrangements allowed for the correct diagnosis of connective tissue disease without the development of MF.

Inflamed vitiligo

  1. Top of page
  2. Abstract
  3. Drug-induced reversible lymphoid dyscrasia/drug-induced pseudolymphoma syndrome
  4. Persistent nodular arthropod bite reactions
  5. Secondary syphilis
  6. Lymphomatoid dermatitis
  7. Nodular scabies
  8. Chronic actinic dermatitis (actinic reticuloid)
  9. Fungal infections
  10. Lichen sclerosus et atrophicus
  11. Lichen striatus
  12. Lichenoid keratosis (solitary lichen planus or lichen-planus-like keratosis)
  13. Pigmented purpuric dermatitis
  14. Connective tissue disease/lupus
  15. Inflamed vitiligo
  16. Regressed malignant melanoma
  17. Conclusion
  18. References

A case of vitiligo demonstrating a moderately dense perivascular and interstitial lymphocytic infiltrate with exocytosis into the epidermis and follicular epithelium was reported.30 This pattern initially suggested hypopigmented MF. However, there was retention of pan-T-cell markers, and TCR genome analysis did not reveal a clonal rearrangement. Therefore, a diagnosis of MF was ruled out. Immunostaining revealed decreased numbers of melanocytes, suggesting possible vitiligo. Six months later, the lesion depigmented, confirming the diagnosis of vitiligo.

Regressed malignant melanoma

  1. Top of page
  2. Abstract
  3. Drug-induced reversible lymphoid dyscrasia/drug-induced pseudolymphoma syndrome
  4. Persistent nodular arthropod bite reactions
  5. Secondary syphilis
  6. Lymphomatoid dermatitis
  7. Nodular scabies
  8. Chronic actinic dermatitis (actinic reticuloid)
  9. Fungal infections
  10. Lichen sclerosus et atrophicus
  11. Lichen striatus
  12. Lichenoid keratosis (solitary lichen planus or lichen-planus-like keratosis)
  13. Pigmented purpuric dermatitis
  14. Connective tissue disease/lupus
  15. Inflamed vitiligo
  16. Regressed malignant melanoma
  17. Conclusion
  18. References

In some instances, malignant melanomas may pose a diagnostic challenge and can vary from benign nevoid appearance to amelanotic spindle cell lesions resembling mesenchymal tumors. Recently, a case of partially regressed malignant melanoma with a dense lymphocytic response and striking epidermotropism closely resembling MF was reported. The predominant CD8 positivity of the infiltrate and HMB45 and S100 positivity of the melanoma cells led to the correct diagnosis of regressing malignant melanoma, but the authors caution that regressed malignant melanoma may present a diagnostic pitfall if one is not careful.31

Conclusion

  1. Top of page
  2. Abstract
  3. Drug-induced reversible lymphoid dyscrasia/drug-induced pseudolymphoma syndrome
  4. Persistent nodular arthropod bite reactions
  5. Secondary syphilis
  6. Lymphomatoid dermatitis
  7. Nodular scabies
  8. Chronic actinic dermatitis (actinic reticuloid)
  9. Fungal infections
  10. Lichen sclerosus et atrophicus
  11. Lichen striatus
  12. Lichenoid keratosis (solitary lichen planus or lichen-planus-like keratosis)
  13. Pigmented purpuric dermatitis
  14. Connective tissue disease/lupus
  15. Inflamed vitiligo
  16. Regressed malignant melanoma
  17. Conclusion
  18. References

Differentiation of MF from its histologic mimickers remains one of the greatest diagnostic challenges in dermatopathology. Accurate diagnosis of MF in skin biopsy correlates significantly with the experience, skill and training of the dermatopathologist, and consultation with a trained dermatopathologist is highly recommended when the diagnosis is in question.11 Diagnosis must be based on a constellation of clinical and histologic criteria and never a single finding in order to accurately confirm the diagnosis when features of MF are present.32,33 This is exemplified by the results of TCR gene rearrangement studies in MF and benign inflammatory dermatoses which may mimic MF. Early patch-stage MF frequently lacks a detectable clonal rearrangement,34 and benign inflammatory dermatoses occasionally have a clonal rearrangement.34,35 This emphasizes the need for clinicopathologic correlation when interpreting the results of clonality studies. While several authors have suggested evolving histologic criteria for the diagnosis of cutaneous T-cell lymphoma over the past several years,36–39 ultimately, clinicopathologic correlation is essential when differentiating MF from its histologic mimickers.

References

  1. Top of page
  2. Abstract
  3. Drug-induced reversible lymphoid dyscrasia/drug-induced pseudolymphoma syndrome
  4. Persistent nodular arthropod bite reactions
  5. Secondary syphilis
  6. Lymphomatoid dermatitis
  7. Nodular scabies
  8. Chronic actinic dermatitis (actinic reticuloid)
  9. Fungal infections
  10. Lichen sclerosus et atrophicus
  11. Lichen striatus
  12. Lichenoid keratosis (solitary lichen planus or lichen-planus-like keratosis)
  13. Pigmented purpuric dermatitis
  14. Connective tissue disease/lupus
  15. Inflamed vitiligo
  16. Regressed malignant melanoma
  17. Conclusion
  18. References
  • 1
    Massone C, Kodama K, Kerl H, Cerroni L. Histopathologic features of early (patch) lesions of mycosis fungoides: a morphologic study of 745 biopsy specimens from 427 patients. Am J Surg Pathol 2005; 29: 550.
  • 2
    Wolf R, Kahane E, Sandbank M. Mycosis fungoides-like lesions associated with phenytoin therapy. Arch Dermatol 1985; 121: 1181.
  • 3
    Horn TD, Hiatt KM. Cutaneous toxicities of drugs. In ElderDE, ElenitsasR, JohnsonBL, MurphyGF, eds. Lever’s histopathology of the skin. New York: Lippincott Williams and Wilkins, 2005; 331.
  • 4
    Clark SH, Duvic M, Prieto VG. Mycosis fungoides-like reaction in a patient treated with Gleevec. J Cutan Pathol 2003; 30: 279.
  • 5
    Terhune MH, Stibbe J, Siegle RJ. Nodule on the cheek of an 81-year-old woman. Persistent arthropod bite reaction (cutaneous T-cell pseudolymphoma). Arch Dermatol 1999; 135: 1543, 1546.
  • 6
    Hwong H, Jones D, Prieto VG, Schulz C, Duvic M. Persistent atypical lymphocytic hyperplasia following tick bite in a child: report of a case and review of the literature. Pediatr Dermatol 2001; 18: 481.
  • 7
    McComb ME, Telang GH, Vonderheid EC. Secondary syphilis presenting as pseudolymphoma of the skin. J Am Acad Dermatol 2003; 49 (2 Suppl Case reports): S174.
  • 8
    Orbaneja JG, Diez LI, Lozano JL, Salazar LC. Lymphomatoid contact dermatitis: a syndrome produced by epicutaneous hypersensitivity with clinical features and a histopathologic picture similar to that of mycosis fungoides. Contact Dermatitis 1976; 2: 139.
  • 9
    Fisher AA. Allergic contact dermatitis mimicking mycosis fungoides. Cutis 1987; 40: 19.
  • 10
    Ackerman AB, Breza TS, Capland L. Spongiotic simulants of mycosis fungoides. Arch Dermatol 1974; 109: 218.
  • 11
    James WD, Berger TG, Elston DM., eds. Cutaneous lymphoid hyperplasia, cutaneous T-cell lymphoma, other malignant lymphomas, and allied diseases. In JamesWD, BergerTG, ElstonDM, eds. Andrew’s diseases of the skin: clinical dermatology. Philadelphia: WB Saunders, 2006; 730.
  • 12
    Murphy GF, Schwarting R. Cutaneous lymphomas and leukemias. In ElderDE, ElenitsasR, JohnsonBL, MurphyGF, eds. Lever’s histopathology of the skin. New York: Lippincott Williams and Wilkins, 2005; 950.
  • 13
    Wall LM. Lymphomatoid contact dermatitis due to ethylenediamine dihydrochloride. Contact Dermatitis 1982; 8: 51.
  • 14
    Sellheyer K, Haneke E. Protozoan diseases and parasitic infestations. In ElderDE, ElenitsasR, JohnsonBL, MurphyGF, eds. Lever’s histopathology of the skin. New York: Lippincott Williams and Wilkins, 2005; 641.
  • 15
    Walton S, Bottomley WW, Wyatt EH, Bury HP. Pseudo T-cell lymphoma due to scabies in a patient with Hodgkin’s disease. Br J Dermatol 1991; 124: 277.
  • 16
    Ploysangam T, Breneman DL, Mutasim DF. Cutaneous pseudolymphomas. J Am Acad Dermatol 1998; 38: 877.
  • 17
    Ive FA, Magnus IA, Warin RP, Jones EW. “Actinic reticuloid”: a chronic dermatosis associated with severe photosensitivity and the histological resemblance to lymphoma. Br J Dermatol 1969; 81: 469.
  • 18
    Toonstra J, Henquet CJ, Van Weelden H, Van Der Putte SC, Van Vloten WA. Actinic reticuloid: a clinical, photobiologic, histopathologic and follow-up study of 16 patients. J Am Acad Dermatol 1989; 21: 205.
  • 19
    Bakels V, Van Oostveen JW, Preesman AH, Meijer CJ, Willemze R. Differentiation between actinic reticuloid and cutaneous T cell lymphoma by T cell receptor gamma gene rearrangement analysis and immunophenotyping. J Clin Pathol 1998; 51: 154.
  • 20
    Al-Amiri A, Chatrath V, Bhawan J, Stefanato CM. The periodic acid-Schiff stain in diagnosing tinea: should it be used routinely in inflammatory skin diseases? J Cutan Pathol 2003; 30: 611.
  • 21
    Capella GL, Altomare GF. Mycosis on mycosis fungoides: zoophilic dermatophytosis selectively superimposed on pre-existing cutaneous T-cell lymphoma (mycosis fungoides) plaques. Mycoses 2003; 46: 67.
  • 22
    Citarella L, Massone C, Kerl H, Cerroni L. Lichen sclerosus with histopathologic features simulating early mycosis fungoides. Am J Dermatopathol 2003; 25: 463.
  • 23
    Gianotti R, Restano L, Grimalt R, Berti E, Alessi E, Caputo R. Lichen striatus – a chameleon: a histopathological and immunohistological study of forty-one cases. J Cutan Pathol 1995; 22: 18.
  • 24
    Mobini N, Toussaint S, Kamino H. Noninfectious erythematous, papular, and squamous diseases. In ElderDE, ElenitsasR, JohnsonBL, MurphyGF, eds. Lever’s histopathology of the skin. New York: Lippincott Williams and Wilkins, 2005; 201.
  • 25
    Al-Hoqail IA, Crawford RI. Benign lichenoid keratoses with histologic features of mycosis fungoides: clinicopathologic description of a clinically significant histologic pattern. J Cutan Pathol 2002; 29: 291.
  • 26
    Toro JR, Sander CA, LeBoit PE. Persistent pigmented purpuric dermatitis and mycosis fungoides: simulant, precursor, or both? A study by light microscopy and molecular methods. Am J Dermatopathol 1997; 19: 108.
  • 27
    Weedon D. Cutaneous infiltrate-lymphomatous and leukemic: mycosis fungoides. In WeedonD, ed. Skin pathology. New York: Churchill Livingstone, 2002; 1104.
  • 28
    Friss AB, Cohen PR, Bruce S, Duvic M. Chronic cutaneous lupus erythematosus mimicking mycosis fungoides. J Am Acad Dermatol 1995; 33: 891.
  • 29
    Magro CM, Crowson AN, Harrist TJ. Atypical lymphoid infiltrates arising in cutaneous lesions of connective tissue disease. Am J Dermatopathol 1997; 19: 446.
  • 30
    Horn TD, Abanmi A. Analysis of the lymphocytic infiltrate in a case of vitiligo. Am J Dermatopathol 1997; 19: 400.
  • 31
    Menasce LP, Shanks JH, Howarth VS, Banerjee SS. Regressed cutaneous malignant melanoma mimicking lymphoma: a potential diagnostic pitfall. Int J Surg Pathol 2005; 13: 281.
  • 32
    Lee MW, Lee DK, Choi JH, Moon KC, Koh JK. Clinicopathologic study of cutaneous pseudolymphomas. J Dermatol 2005; 32: 594.
  • 33
    Cotta AC, Cintra ML, De Souza EM, Magna LA, Vassallo J. Reassessment of diagnostic criteria in cutaneous lymphocytic infiltrates. Sao Paulo Med J 2004; 122: 161.
  • 34
    Alessi E, Coggi A, Venegoni L, Merlo V, Gianotti R. The usefulness of clonality for detection of cases clinically and/or histopathologically not recognized as cutaneous T-cell lymphoma. Br J Dermatol 2005; 153: 368.
  • 35
    Ponti R, Quaglino M, Novelli M, et al. T-cell receptor γ gene rearrangement by multiplex polymerase chain reaction/heteroduplex analysis in patients with cutaneous T-cell lymphoma (mycosis fungoides/Sezary syndrome) and benign inflammatory disease: correlation with clinical, histological and immunophenotypical findings. Br J Dermatol 2005; 153: 565.
  • 36
    Nickoloff BJ. Light-microscopic assessment of 100 patients with patch/plaque-stage mycosis fungoides. Am J Dermatopathol 1988; 10: 469.
  • 37
    King-Ismael D, Ackerman AB. Guttate parapsoriasis/digitate dermatosis (small plaque parapsoriasis) is mycosis fungoides. Am J Dermatopathol 1992; 14: 518.
  • 38
    Smoller BR, Bishop K, Glusac E, Kim YH, Hendrickson M. Reassessment of histologic parameters in the diagnosis of mycosis fungoides. Am J Surg Pathol 1995; 19: 1423.
  • 39
    Santucci M, Biggeri A, Feller AC, Burg G. Accuracy, concordance, and reproducibility of histologic diagnosis in cutaneous T-cell lymphoma: an EORTC Cutaneous Lymphoma Project Group Study. European Organization for Research and Treatment of Cancer. Arch Dermatol 2000; 136: 497.