Mycosis fungoides with prominent reactive B-cell infiltration.

After identifying prominent eccrine infiltration by atypical lymphocytes in a biopsy of tumor stage mycosis fungoides (MF), we sought to determine the pattern of eccrine epithelial infiltration in MF. The frequency, intensity, and distribution of infiltration of eccrine gland structures, including acrosyringium, duct and coil epithelium, was studied by examining 71 biopsy specimens from 42 patients with MF in which eccrine structures were present. These were obtained from a retrospective review of pathologic specimens from Duke University Medical Center from 1992 and 1993. At least focal eccrine infiltration was noted in 23 of the 71 biopsy specimens (32%). Immunohistochemical confirmation of T-lymphocyte phenotype was performed in the 23 cases with positive reaction to antibodies CD3 and CD45RO and negative reaction with CD20. Folliculosebaceous units were present in 22 of the 71 biopsy specimens and were at least focally involved by MF in 11 (50%) in this series. A control group of biopsy specimens of reactive dermatoses were characterized by more superficial location of lymphocytes, with more spongiosis and epithelial degenerative changes. These findings further illustrate the epitheliotropic behavior of MF.

To verify the incidence and the possible diagnostic use of detecting adnexotropism in mycosis fungoides (MF). We reviewed the frequency and the intensity of the eccrine and follicular infiltration in 104 biopsy specimens from indisputable cases of MF and in a control group of 20 biopsy specimens of spongiotic dermatitis. Syringohyperplasia and follicular mucinosis were also evaluated. A prominent eccrine infiltration was noted in 32 of 104 specimens (30%). Marked acrosyringial and ductal eccrine hyperplasia was present in 5 specimens (5%). In 13 of the 32 specimens with prominent eccrine infiltration (40%), epidermotropism was slight or less evident than syringotropism. Follicular structures were visible in 59 specimens and significantly infiltrated in 57%. Follicular mucinosis was found in 5 (8.4%). In the control group of spongiotic dermatitis, a significant eccrine and follicular infiltration was found only in case (5%). Adnexal (eccrine gland and follicle) infiltration may be a useful diagnostic tool in MF, particularly in those in which epidermotropism is slight.

Early generalized morphea can clinically mimic mycosis fungoides. The microscopic features of early inflammatory morphea may show variable degrees of infiltration and do not have the characteristic dermal collagen sclerosis. We report the case of a 63-year-old female patient who presented with a 2-month history of an asymptomatic skin rash. Physical examination revealed multiple erythematous to dusky patches on the trunk and thighs, resembling the patch stage of mycosis fungoides. Two skin biopsies were performed, both of which showed prominent interstitial lymphoid infiltration in the reticular dermis without dermal sclerosis. Small lymphocyte exocytosis and lining along the dermal-epidermal junction were observed focally in the epidermis. Small clusters of plasma cells and eosinophils were observed in perivascular areas. Although no predominant clonality was found for CD4 and CD8 stains, 50% loss of CD5 antigen and 90% loss of CD7 antigen expression were apparent in immunohistochemical studies. Subsequent blood tests showed a normal blood cell count and positive human T-lymphotropic virus Type 1 antibodies. The overall findings suggested interstitial mycosis fungoides or early adult T-cell lymphoma-leukemia. The patient refused aggressive treatment, and 3 months later, she presented with indurated plaques from the previous rash. A repeat biopsy revealed the typical features of morphea. This report discussed the pitfalls in the clinical and histopathological diagnosis of early generalized inflammatory morphea that both clinicians and pathologists should consider.

T cells expressing the γδ T-cell receptor (TCR) (γδ T cells) are found in normal epithelial tissues such as the skin. However, the proportions of γδ T cells that may be observed in commonly encountered cutaneous diseases with a prominent lymphocytic infiltrate have not been elucidated. Our pathology database was searched for cases of mycosis fungoides, erythema multiforme, graft-versus-host disease, lichen planus, lupus panniculitis and spongiotic dermatitis. Immunostaining for CD3, βF1 and the TCR γ chain was performed on formalin-fixed paraffin-embedded specimens retrieved from these cases to determine the normal range of γδ T cells in these diseases. In 100 of the 101 cases studied (99.0%), γδ T cells accounted for less than 10% of the T-cell infiltrate. Furthermore, γδ T cells were essentially absent in 74 cases (73.3%). These results suggest that γδ T cells very rarely account for more than 10% of the lymphocytic infiltrate in common inflammatory or infiltrative processes of the skin. Any case of suspected mycosis fungoides or interface dermatitis that possesses more than 10% γδ T cells should raise consideration for further investigation.

CD8+ T-cell lymphomas presenting in the skin are rare. We describe the clinical and histological features of 18 patients with CD8+ cutaneous T-cell tumors, which have been divided into four groups. Seven patients had precedent long histories of rashes, which progressively spread in a presentation similar to that of CD4+ mycosis fungoides (MF). Three patients had long-standing localized plaques consistent with a pagetoid reticulosis (PR) pattern. Two patients presented with erythroderma and had peripheral blood involvement consistent with a Sezary syndrome (SS) pattern and had rapidly progressive clinical courses. Six patients presented with cutaneous nodules of varying sizes and had variable outcomes, with two having rapidly progressive disease, two with indolent recurrences and a further two with complete responses to treatment. Histologically, 12 of the 18 cases showed an epidermotropic tumor infiltrate that was most marked in the three PR cases. Prominent periadnexal infiltration was seen in 11 cases. Similar to CD4+ MF, the skin-homing antigen, (cutaneous lymphocyte antigen: CLA), was strongly expressed in 13 of 16 tested cases. Expression of the cytotoxic granule protein granzyme B was noted in a majority of tumor cells in only three of 16 tested cases. We conclude that approximately half of CD8+ cutaneous T-cell lymphomas clinically and histologically resemble CD4+ MF/SS, whereas presentation as discrete nodular lesions are more common in CD8+ tumors as compared to those that express CD4.

Mycosis fungoides (MF) is the most common form of primary cutaneous lymphoma with a broad clinicopathological spectrum. Unusual histopathologic patterns of MF include lichenoid, interstitial, folliculotropic, spongiotic, granulomatous, and many others. Several cases of unusual lichenoid reaction characterized by a mixed lichenoid inflammatory infiltrate with prominent infiltration of the papillary dermis and epidermis by multinucleated giant cells were described under the name of "giant cell lichenoid dermatitis," most of them were considered to represent a drug eruption. Herein, we describe a 77-year-old woman with a 5-year history of MF displaying microscopic features of giant cell lichenoid dermatitis. Histology revealed a dense band-like lichenoid epidermotropic infiltrate composed of CD4 small to medium-sized lymphocytes with cerebriform nuclei with the presence of multinucleated giant cells in the papillary dermis, within the epidermis, and some hair follicles. Monoclonal TCR gene rearrangement was detected using PCR. To the best of our knowledge, this pattern was never described in MF.

Primary cutaneous CD4 small/medium-sized pleomorphic T-cell lymphoma (PCSTCL) has recently emerged as a distinct clinicopathological entity. Because of a considerable degree of overlap with pseudolymphoma, the diagnosis is often challenging. Preliminary studies suggest that nuclear upregulation of calcineurin/nuclear factor of activated T cells (NFAT) may play a role in lymphomagenesis. 137 cases (70 males and 67 female, mean age = 55) of various forms of cutaneous T-cell and B-cell infiltration were evaluated for NFATc1 expression. The study comprised 18 cases of PCSTCL, 45 cases of mycosis fungoides (MF), 5 cases of lymphomatoid papulosis (LyP), 5 cases of anaplastic large-cell lymphoma (ALCL), 8 cases of other forms of peripheral T-cell lymphoma, not otherwise specified, 12 precursor lesions of MF (ie, cutaneous T-cell dyscrasias), 35 cases of pseudolymphomas, 8 primary cutaneous B-cell lymphoma, and 1 chronic lymphocytic leukemia. The number of cells exhibiting a nuclear stain was counted per 10 high-power field and 2-tailed statistical analysis was used for comparison of nuclear NFATc1 expression between primary PCSTCL and all other groups. A P-value <0.05 was considered to indicate statistical significance. All cases of PCSTCL showed nuclear staining for NFATc1 (mean = 296 ± 236) with no cases in which an exclusive cytoplasmic stain was observed. The cells exhibiting this staining pattern were oftentimes larger manifesting other features of a follicular helper T-cell phenotype, such as variable positivity for PD1, ICOS, CXCL13, and BCL6. In comparison, an exclusively cytoplasmic stain was observed in 29 cases of MF; in few cases, rare nuclear staining cells were observed averaging less than 10 per high-power field (P = 0.0001). These positive staining cases were not only limited to tumor-stage MF but also encompassed patch- and plaque-stage lesions and follicular variants of MF. The same pattern was observed in cases of T-cell dyscrasia (mean = 3 ± 3, P = 0.0001) and pseudolymphoma (mean = 2 ± 3, P = 0.0001), both revealing a dominant cytoplasmic staining pattern. In pseudolymphomatous folliculitis, a greater extent of nuclear staining for NFATc1 was observed compared with other forms of pseudolymphoma. No significant difference was seen between MF and T-cell dyscrasia or pesudolymphomas excluding pseudolymphotous folliculitis. Anaplastic large-cell lymphoma cases showed an almost exclusive cytoplasmic staining pattern with rare nuclear staining (mean = 55 ± 102, P = 0.0001); similar results were observed in LyP (mean = 17 ± 15, P = 0.004). Cutaneous B-cell lymphomas showed a similar extent of staining as that noted for PCSTCL. The greatest extent of staining was observed in chronic lymphocytic leukemia. A significant difference was noted between the extent of nuclear staining in PCSTCL and other forms of primary cutaneous T-cell lymphoma, type unspecified (mean = 22 ± 43, P = 0.0002), although not between PCSTCL and B-cell lymphoma. NFAT signaling plays a critical role in peripheral T-cell activation after T cell receptor engagement. When assessing T-cell-rich infiltrates where the differential diagnosis is largely between a PCSTCL and pseudolymphoma, a significant degree of nuclear staining of lymphocytes would be more in keeping with a diagnosis of PCSTCL. Upregulation of the NFAT pathway is not a feature of tumor progression in the setting of MF.

Mycosis fungoides (MF) represents the most common type of cutaneous lymphoma. The diagnosis of MF may occasionally be challenging, particularly for variants of MF such as folliculotropic MF, syringotropic MF and granulomatous MF. Herein, we describe a case of MF in which syringotropism and a prominent granulomatous reaction were noted around the affected eccrine gland. This case represents a rare example of MF with multiple unusual histopathological features, including syringotropism, a granulomatous reaction and a reactive B-cell proliferation.

Introduction: Annular lichenoid dermatitis of youth (ALDY) is a rare and underreported dermatologic condition. It primarily affects children and adolescents. Clinically, ALDY presents as erythematous annular macules or plaques with raised borders and hypopigmented centers, predominantly affecting the trunk and flexural areas. The etiology remains unknown, and the condition poses a diagnostic challenge due to its resemblance to other annular dermatoses. Case Presentation: A 5-year-old female presented with asymptomatic annular erythematous lesions on the trunk, abdomen, lumbar region, and flanks. Initial differential diagnoses included annular erythema, tinea corporis, morphea, and mycosis fungoides. A mycological examination was negative, and symptomatic treatment with hydrocortisone and pimecrolimus led to temporary lesion resolution, but recurrence followed treatment cessation. A skin biopsy revealed histopathological features characteristic of ALDY, including basal layer vacuolization and a prominent lichenoid lymphocytic infiltrate. Immunohistochemical analysis supported the diagnosis. Conclusion: ALDY remains a diagnostic challenge due to its clinical overlap with other annular dermatoses. Histopathological examination is essential for definitive diagnosis. The chronic and recurrent nature of ALDY underscores the importance of long-term management strategies, including topical corticosteroids and immunomodulators. Awareness of ALDY among dermatologists can aid in early recognition and appropriate management, ultimately improving patient outcomes.

Unilesional (solitary) mycosis fungoides (MF) is a rare variant characterized clinically by the presence of a single contiguous area of skin involvement covering less than 5% of the body surface and histopathologically by features identical to those seen in classical MF. Angiocentricity (angiodestruction) is mostly a feature of primary or secondary cutaneous lymphomas with an aggressive course and poor outcome, with only very few reports of MF with angiocentric pattern. The authors report an unusual case of solitary patch-stage MF with hemorrhagic features, characterized histologically by epidermotropic and angiocentric (angiodestructive) infiltrate and a reactive B-cell component appearing as lymphoid follicles.

Primary Cutaneous Small to Medium-Size CD4+ Pleomorphic T-Cell Lymphoma: 48 Patients from Two Independent Centers and Revaluation of Clinico-Histological Criteria for Differential Diagnosis from Other CTCL

A clinical and histologic mycosis fungoides simulant occurring as a T-cell infiltrate coexisting with B-cell leukemia cutis

The role of tumor infiltrating immune cells in cancer development and progression is a new, promising field in oncological research. An increasing number of novel anti-cancer agents are focussing on the tumor microenvironment. Various studies have reported on B-cell infiltrates in mycosis fungoides (MF), but despite the substantial volume of interesting findings, solid evidence regarding their specific role in cancer is still vague. We present a case of tumor stage MF responding to rituximab. We support the hypothesis that lymphoma-infltrating B-cells have a significant impact on cutaneous lymphoma course and seem to be both an important and effective therapeutic target. The reduction of B-cell population led to disease's overall remission, probably by restoring patient's immunologic tumor control.

Folliculotropic mycosis fungoides is a variant of mycosis fungoides showing tropism for hair follicles. There is prominent infiltration of the follicular epithelium by atypical lymphocytes. Disruption of follicular architecture is also present and may manifest in several forms: cystic change, follicular destruction with granuloma formation, and basaloid folliculolymphoid hyperplasia. Cases of folliculotropic mycosis fungoides with mucin deposition must be distinguished from benign idiopathic follicular mucinosis.

Primary cutaneous CD4-positive small/medium-sized pleomorphic T-cell lymphoma: a clonal T-cell lymphoproliferative disorder with indolent behavior