Cutaneous Richter syndrome: report of 3 cases from one institution.

BACKGROUND: Richter syndrome (RS) is large-cell transformation of chronic lymphocytic leukemia (CLL). It commonly involves lymph nodes and bone marrow, but may rarely manifest in skin. Certain triggering factors, such as Epstein-Barr virus infection and p53 overexpression, have been implicated in the pathogenesis of RS. Here, we present 3 cases of cutaneous RS from our institution with a follow-up period of up to 8 years. OBJECTIVE: We present a series of cutaneous RS from a single institution with the longest follow-up period (up to 8 years) to date. METHODS: Clinical characteristics were collected and histopathological findings of skin biopsy specimens were analyzed. RESULTS: All 3 patients had prior CLL and later developed cutaneous RS lesions. The mean age at the diagnosis of cutaneous RS was 67 years old. The time intervals between CLL and cutaneous RS were 3 to 8 years. Skin biopsy specimens demonstrated dermal nodular or perivascular infiltrates of large B cells, showing similar immunophenotypes to the lesional cells in the original CLL. Overexpression of p53 and positive stain for Epstein-Barr virus--encoded small RNA was found in one patient. One patient remained alive 8 years after the diagnosis whereas the other two died of the disease at 5 years and 3 weeks, respectively, after the onset of cutaneous RS. LIMITATIONS: Three patients with RS were followed up for up to 8 years. CONCLUSIONS: Our findings suggested that, in contrast to extracutaneous RS, cutaneous RS generally has a less aggressive course with longer survival unless other worse prognostic factors are present.

Nephrogenic systemic fibrosis: a report of 29 cases.

OBJECTIVE: The purpose of this study was to determine the incidence of nephrogenic systemic fibrosis and its relation to renal failure and the administration of gadolinium-based contrast material at an academic medical center. MATERIALS AND METHODS: A dermatopathology database was searched to identify patients in whom nephrogenic systemic fibrosis was diagnosed. The medical records of these patients were reviewed. Renal function concurrent with any administration of gadolinium-based contrast material was assessed, as was patient outcome. A database of patients undergoing long-term dialysis was reviewed separately to determine how many had received gadolinium and the frequency of nephrogenic systemic fibrosis among these patients. RESULTS: Twenty-nine patients were found to have had nephrogenic systemic fibrosis between November 15, 1999, and December 31, 2006. It was known that gadolinium-based contrast material had been administered to 25 of these patients before diagnosis. All 29 patients had compromised renal function (27 had chronic renal failure, and two had acute renal failure). Determination of the temporal relation between gadolinium-based contrast administration and symptom onset often was difficult. Only eight patients had severe morbidity. Nephrogenic systemic fibrosis developed in 12 (2.9%) of 414 patients undergoing long-term dialysis who received gadolinium-based contrast material. CONCLUSION: We confirm the strong association between nephrogenic systemic fibrosis and gadolinium-based contrast administration. Although the use of high doses of gadolinium and the occurrence of chronic renal failure have been implicated in other reports, several of our patients received standard doses of gadolinium, and two had transient acute renal failure before diagnosis. Most patients had mild or moderate symptoms. Nephrogenic systemic fibrosis developed in 2.9% of patients undergoing long-term dialysis who received gadolinium-based contrast material but in none of the long-term dialysis patients who did not receive gadolinium-based contrast material.

Expression of polycomb group protein EZH2 in nevi and melanoma.

BACKGROUND: Enhancer of zeste homolog 2 (EZH2), a polycomb group protein that regulates the cell cycle, has recently been implicated in the progression of several human cancers. We sought to determine the pattern of EZH2 expression in benign and malignant melanocytic tumors to see if EZH2 might play a role in melanoma pathogenesis and progression. METHODS: We identified and reviewed 11 compound nevi, 13 dysplastic nevi, 13 Spitz nevi, 9 in situ melanomas, 10 non-metastatic invasive melanomas and 19 melanomas metastatic to lymph nodes from the University of Michigan pathology archives. Sections immunostained with anti-EZH2 antibody were scored independently and blindly for staining intensity on a scale of 1-4 by three dermatopathologists. Results were analyzed and compared statistically. RESULTS: We observed an incremental increase in EZH2 expression from benign nevi to melanoma: scores of 1.18 and 1.08 for ordinary and dysplastic nevi, 1.7 and 1.78 for Spitz nevi and in situ melanoma, and 1.9 and 3.0 for invasive and metastatic melanoma, respectively. EZH2 expression for metastatic melanoma was significantly higher compared with invasive and in situ melanoma and benign nevi (p < or = 0.01). CONCLUSIONS: EZH2 protein levels increase incrementally from benign nevi to melanoma, which suggests that EZH2 may play a role in the pathogenesis and progression of melanoma.

Telomerase expression in sebaceous lesions of the skin.

BACKGROUND: Recent studies have demonstrated telomerase expression in ophthalmologic sebaceous carcinoma and have suggested possible diagnostic utility in distinguishing these neoplasms from sebaceous adenomas. The aim of this study was to evaluate telomerase expression via human telomerase reverse transcriptase (hTERT) immunohistochemical staining in a spectrum of sebaceous lesions of the skin. METHODS: Paraffin-embedded sections from sebaceous hyperplasia (11), nevus sebaceus (22), sebaceous adenoma (19), sebaceoma (11), and sebaceous carcinoma (14) were evaluated for intensity (0 to 3+) and pattern of anti-hTERT staining. RESULTS: Strong (2 to 3+) hTERT staining was observed in nucleoli of germinative cells and immature sebocytes in all sebaceous lesions, whereas mature sebocytes were negative. The distribution pattern paralleled features seen by routine haematoxylin and eosin-stained sections. CONCLUSIONS: All hyperplastic and neoplastic sebaceous skin lesions expressed hTERT in this immunohistochemical study. The pattern of staining was predictive of the histologic pattern of the process but does not significantly add to our diagnostic armamentarium of sebaceous lesions.

Anti-oncogenic role of the endoplasmic reticulum differentially activated by mutations in the MAPK pathway.

Dysfunction of the endoplasmic reticulum (ER) has been reported in a variety of human pathologies, including cancer. However, the contribution of the ER to the early stages of normal cell transformation is largely unknown. Using primary human melanocytes and biopsies of human naevi (moles), we show that the extent of ER stress induced by cellular oncogenes may define the mechanism of activation of premature senescence. Specifically, we found that oncogenic forms of HRAS (HRAS(G12V)) but not its downstream target BRAF (BRAF(V600E)), engaged a rapid cell-cycle arrest that was associated with massive vacuolization and expansion of the ER. However, neither p53, p16(INK4a) nor classical senescence markers--such as foci of heterochromatin or DNA damage--were able to account for the specific response of melanocytes to HRAS(G12V). Instead, HRAS(G12V)-driven senescence was mediated by the ER-associated unfolded protein response (UPR). The impact of HRAS on the UPR was selective, as it was poorly induced by activated NRAS (more frequently mutated in melanoma than HRAS). These results argue against premature senescence as a converging mechanism of response to activating oncogenes and support a direct role of the ER as a gatekeeper of tumour control.

BRAF and NRAS mutations in spitzoid melanocytic lesions.

BRAF mutations are common events in a variety of melanocytic nevi and primary cutaneous melanomas. We have previously found BRAF mutations in 82% of nevi, consisting of congenital, common acquired and dysplastic types, and 33% of primary cutaneous melanomas other than the spitzoid type, similar to other published reports. A small number of studies have evaluated Spitz nevi and have failed to detect any lesions possessing a BRAF mutation. Only one study included categories of atypical Spitz nevus and borderline lesions suspected to be spitzoid melanomas, along with classic Spitz nevi and spitzoid melanomas. We examined a spectrum of spitzoid lesions that included 48 Spitz nevi, some with atypical features, seven atypical (borderline) Spitz tumors, and 13 spitzoid melanomas. BRAF mutations were detected in 12 of 68 spitzoid lesions, of which two were spitzoid melanomas and 10 were Spitz nevi. Five of the 10 Spitz nevi with BRAF mutations were altered by more than usual cytologic atypia and/or architectural atypia overlapping with dysplastic nevi, or irritation/inflammation; one desmoplastic Spitz nevus had a BRAF mutation. These results indicate that a small subset of Spitz nevi, some with atypical histologic features, possess BRAF mutations. Therefore, the BRAF mutational status does not separate all Spitz nevi from spitzoid melanomas and non-Spitz types of melanocytic proliferations, contrary to previous reports.

hTERT expression in melanocytic lesions: an immunohistochemical study on paraffin-embedded tissue.

BACKGROUND: Telomerase plays a role in the immortalization of cells and carcinogenesis. Previous studies have yielded conflicting results on whether human telomerase RNA (hTER) expression differs in nevi, atypical nevi and melanomas using polymerase chain reaction-based telomeric repeat amplification protocol or in situ hybridization assays. The aim of this study was to evaluate human telomerase reverse transcriptase (hTERT) staining in melanocytic lesions on paraffin-embedded tissues. METHODS: Paraffin-embedded sections from 12 acquired nevi, seven dysplastic nevi, 11 Spitz nevi, eight primary invasive melanomas, and three metastatic melanomas were studied for staining intensity (0-3+) and percentage of labeled cells with anti-hTERT. RESULTS: hTERT staining was observed in most cells (>75%), in all but three lesions, and was of greater intensity in the nucleus, especially the nucleolus, compared with the cytoplasm. Spitz nevi tended to have weaker hTERT staining (mean = 1.7) compared with acquired nevi (mean = 2.2), dysplastic nevi (mean = 2.4), primary melanomas (mean = 2.4), or metastatic melanomas (mean = 3). CONCLUSIONS: Although telomerase activity was weaker in Spitz nevi, there was overlap with other nevi and primary invasive melanomas in our small series. Thus, hTERT expression does not appear to be a reliable adjunct to the histological diagnosis of primary melanocytic lesions.

Cluster designation 5 staining of normal and non-lymphoid neoplastic skin.

BACKGROUND: Immunohistochemical staining for cluster designation 5 (CD5) has been found to label a variety of non-lymphoid tumors. METHODS: A variety of eccrine, apocrine, follicular, epithelial, and pagetoid lesions were selected and stained with an anti-CD5 monoclonal antibody (Novocastra Labs, Newcastle upon Tyne, UK, clone 4C7) by immunohistochemistry. The intensity of positive cytoplasmic staining was graded semiquantitatively (1+ weak staining, 2+ strong staining). Additionally, the percentage of positive lesional cells was placed in one of four categories: >75%, 25-75%, 1-25%, and <1%. RESULTS: Within normal skin, CD5 labeled lymphocytes, apocrine glands, deep dermal eccrine glands, and smooth muscle (weak). The majority of benign and malignant apocrine lesions demonstrated strong focal (36%, n=11)-to-diffuse (64%, n=16) staining. In contrast, labeling of benign eccrine tumors was more focal, tending to localize around ducts (79%, n=19). Microcystic adnexal carcinoma demonstrated focal staining of deeper ductal structures (71%, n=7), whereas desmoplastic trichoepithelioma and basal cell carcinoma showed only rare positive cells. All cases of mammary (n=7) and extramammary (n=8) Paget's disease labeled diffusely for CD5. Pagetoid Bowen's disease (n=6), intraepidermal sebaceous carcinoma (n=3), nor melanoma in situ (n=6) showed any CD5 staining. CONCLUSIONS: Immunohistochemical staining for CD5 is extremely useful in the differential diagnosis of pagetoid epidermal lesions and will mark mammary and extramammary Paget's disease, but not pagetoid Bowen's disease, melanoma in situ, or sebaceous carcinoma.

Desmoplastic and neurotropic melanoma.

BACKGROUND: Desmoplastic and neurotropic melanoma (DNMM) occasionally metastasizes to regional lymph nodes and extranodal sites. The value of sentinel lymph node biopsy (SLNB) has not been demonstrated clearly for patients with DNMM. The authors report on the utility of SLNB in the management of patients with DNMM. METHODS: The authors identified 33 patients with DNMM who were seen during a 5-year period in their institution who underwent lymphatic mapping and SLNB. Clinical and histopathologic data were reviewed. RESULTS: Thirty-three patients with DNMM underwent SLNB (mean Breslow depth, 4.0 mm; median, 2.8 mm). There were 25 male patients and 8 female patients with a median age of 61 years (range, 31-86 years). Fifty-two percent of tumors presented in the head and neck region, and 24% were associated with lentigo maligna. Four of 33 patients (12%) without clinical evidence of metastatic disease who underwent SLNB had at least 1 positive sentinel lymph node. No additional positive lymph nodes were found in subsequent therapeutic regional lymphadenectomy in any of these four patients. CONCLUSIONS: SLNB detected subclinical metastases of DNMM to regional lymph nodes. SLNB at the time of resection can provide useful information to guide early treatment and, coupled with lymphadenectomy in positive patients, may limit tumor spread and prevent recurrence at the draining lymph node basin.

Vascular expression of matrix metalloproteinase-13 (collagenase-3) in basal cell carcinoma.

Matrix metalloproteinase-13 (MMP-13; collagenase-3) was detected in the vasculature from 17 of 20 human basal cell carcinomas as assessed by immunohistology immediately after surgery. In contrast, MMP-1 (interstitial collagenase) was detected in the vasculature of only two of the same specimens. MMP-13 reactivity was also observed in the capillaries of normal human skin taken from the wound margin. Human dermal microvascular endothelial cells as well as human umbilical vein endothelial cells were isolated in culture and examined for MMP-13 expression. By reverse transcription-polymerase chain reaction and Southern blotting, an MMP-13 transcript was detected in unstimulated endothelial cells. The transcript was upregulated in cells treated with 50 nM phorbol myristate acetate (PMA). Western blotting demonstrated the presence of an anti-MMP-13 - immunoreactive protein in culture fluid from both cell sources. Immunoreactivity was stronger in culture fluid from cells treated with interleukin-1alpha (IL-1alpha) than in culture fluid from control cells. Tumor necrosis factor-alpha (TNF-alpha) and PMA also upregulated MMP-13 expression but these agents were not as effective as IL-1alpha. Additionally, reactivity was greater in culture fluid from endothelial cells grown on three-dimensional lattices of polymerized type I collagen than on dried collagen films. These data indicate that endothelial cells in the skin are a source of MMP-13 and that enzyme expression is upregulated under conditions that promote endothelial cell growth and vascular differentiation.

Nephrogenic fibrosing dermopathy: a novel cutaneous fibrosing disorder in patients with renal failure.

BACKGROUND: Nephrogenic fibrosing dermopathy is a newly recognized cutaneous fibrosing disorder marked by the acute onset of induration involving the upper and lower limbs in patients with acute or chronic renal failure. The etiology, pathogenesis, associated clinical conditions (other than renal failure), and ultimate course have not been defined in the few cases studied. Presently, there is no effective treatment, and the condition persists in most patients. METHODS: Clinical and histopathologic data on 13 patients from our institution with the diagnosis of nephrogenic fibrosing dermopathy were reviewed. Several clinical and laboratory parameters were examined to see if any were consistently associated with the disease. Biopsy specimens were analyzed to determine if there was a pattern to the evolution of fibrosis in these patients. RESULTS: All 13 patients had renal failure before disease onset: 8 were undergoing chronic hemodialysis, 2 were undergoing chronic peritoneal dialysis, and 3 with acute renal failure had never undergone dialysis before the development of dermopathy. Most patients had other serious underlying medical conditions. Many patients were taking erythropoietin, cyclosporine, or both before the onset of disease. In transplant patients, no histocompatibility antigens were found to be associated with the disease. There were various laboratory abnormalities, but none were consistently associated with the condition. In skin biopsy specimens taken 7 to 180 days after disease onset, there were histopathologic changes suggestive of a tissue reaction to injury, as well as the development of smooth muscle actin-positive myofibroblasts. CONCLUSION: Nephrogenic fibrosing dermopathy is a novel cutaneous fibrosing disorder that is distinguished from other sclerosing or fibrosing skin disorders by distinctive clinical and histopathologic findings occurring in the setting of renal failure. There were no additional clinical risk factors or laboratory findings common to the 13 patients studied, other than renal failure. The resemblance to a tissue injury reaction and the presence of myofibroblasts in the tissue specimens suggest that fibrogenic cytokines may be involved in the evolution of the disease.

Lymphatic mapping and sentinel lymph node biopsy in the detection of early metastasis from sweat gland carcinoma.

BACKGROUND: Several subtypes of sweat gland carcinoma have been found to demonstrate a propensity to metastasize systemically and to regional lymph nodes. The predictive value and benefit of sentinel lymph node (SLN) biopsy have been established in numerous other malignancies, but to the authors' knowledge there is little literature published to date regarding the use of SLN biopsy in patients with sweat gland carcinoma. In the current study, the authors demonstrated the utility of SLN biopsy in detecting subclinical metastases of sweat gland carcinoma, which may result in early treatment. METHODS: The authors identified five patients with malignant eccrine tumors in whom SLN biopsy was performed at the study institution. Clinical and histopathologic data were reviewed. RESULTS: The five study cases included two cases of aggressive digital papillary adenocarcinoma (both occurring on upper extremity digits), two cases of hidradenocarcinoma (occurring on the knee and foot, respectively), and an eccrine carcinoma (occurring on the scalp). In each biopsy-established case, there was no clinical evidence of metastatic disease, and a wide local excision or amputation was performed with concurrent SLN biopsy. Four of 18 SLNs in 3 of the 5 patients (60%) were found to be positive for metastatic carcinoma, as identified in hematoxylin and eosin stains and/or cytokeratin immunohistochemical stains. All three lymph node-positive patients subsequently underwent regional lymphadenectomy and were found to have no evidence of additional metastases. CONCLUSIONS: The results of the current study demonstrate that SLN biopsy detects subclinical metastases from sweat gland carcinomas to regional lymph nodes. SLN mapping and biopsy at the time of resection can provide useful information with which to guide early treatment. Further studies are necessary to determine whether this procedure results in a survival benefit in patients with sweat gland carcinomas.

Antibody to S100a6 protein is a sensitive immunohistochemical marker for neurothekeoma.

BACKGROUND: Neurothekeoma is a benign tumor of putative peripheral nerve sheath origin. It occurs in a myxoid (classic) variant, cellular variant, and intermediate (mixed) variant. Cellular neurothekeoma (CNT) usually involves the head and neck or extremities of young patients. Histologically, CNT can be confused with melanocytic and fibrohistiocytic lesions. An immunohistochemical antibody panel is often necessary to confirm the histological impression and exclude melanocytic and/or fibrohistiocytic lesions. METHODS: Formalin-fixed, paraffin-embedded archival tissues were evaluated by immunohistochemistry using antibodies specific for S100A6 and PGP9.5 in 11 cases of neurothekeoma (seven cellular, four myxoid). A variety of other antibodies were evaluated by immunohistochemistry at the time of initial diagnosis. RESULTS: All 11 neurothekeoma cases were positive for S100A6 protein (four cases, weak/1+; seven cases, strong/2+), corresponding to 100% sensitivity. In contrast, eight of 11 neurothekeoma cases (73% sensitivity) were positive for PGP9.5. All seven CNT cases were negative for S100B, as expected. CONCLUSIONS: Anti-S100A6 is a highly sensitive antibody for neurothekeomas, including CNT, and, in our experience, is superior in sensitivity to PGP9.5. However, like other antibodies used in evaluating neurothekeomas, S100A6 lacks specificity, as has been demonstrated in previous studies. Nevertheless, S100A6 can be useful in an immunohistochemical antibody panel to evaluate lesions where the differential diagnosis includes CNT.

Mycobacterium marinum infection simulating interstitial granuloma annulare: a report of two cases.

We report two cases of Mycobacterium marinum infection that histologically simulated interstitial granuloma annulare (GA). In one case, an infectious etiology was not suspected in histologic sections, but a tissue culture performed during the patient's clinic visit identified M. marinum, and a subsequent Fite stain revealed mycobacteria. Interstitial granulomatous dermatitis is a rare presentation for cutaneous nontuberculous mycobacteria and has yet to be attributed specifically to M. marinum. In both immunocompetent and immunosuppressed patients, infection with M. marinum should be considered in lesions histologically resembling interstitial GA, particularly when there is clinical suspicion for an infectious process.

Sentinel lymph node biopsy for patients with problematic spitzoid melanocytic lesions: a report on 18 patients.

BACKGROUND: Spindle and/or epithelioid melanocytic proliferations that display overlapping histopathologic features of Spitz nevus and Spitz-like melanoma are diagnostically difficult and controversial melanocytic tumors. There are reports of such lesions metastasizing to regional lymph nodes, with a few widely disseminating, resulting in death. METHODS: The authors reviewed clinical and histopathologic data on all patients with atypical or borderline spitzoid melanocytic proliferations who underwent sentinel lymph node biopsy (SLNB). They examined how frequently histologically problematic or borderline spitzoid melanocytic lesions metastasized to sentinel lymph nodes (SLNs) and which clinical or histologic features, if any, predisposed patients to a higher risk lesion. RESULTS: Six male patients and 12 female patients, ages 5-32 years (mean, 16 years), had tumors ranging in size from 1.2 mm to 7.9 mm (mean, 3.5 mm) in thickness. Atypical histologic features that were present most frequently included incomplete maturation (18 of 18 patients), deep dermal mitoses (16 of 18 patients), nuclear pleomorphism (10 of 18 patients), and focal sheet-like growth (10 of 18 patients). Eight of 18 patients (44%) had SLN metastasis and were offered adjuvant treatment. One of eight patients with SLN positive results who underwent regional lymphadenectomy had one additional involved lymph node. All 18 patients were alive and well with no evidence of recurrent or metastatic disease after a follow-up of 3-42 months (mean, 12 months). CONCLUSIONS: Histologically atypical or borderline spitzoid, melanocytic tumors are diagnostically challenging and controversial melanocytic lesions, some of which represent unrecognized melanomas. SLNB aids in confirming a diagnosis of melanoma and identifies patients who may benefit from early therapeutic lymph node dissection and/or adjuvant therapy.

CD117 (KIT receptor) expression in Merkel cell carcinoma.

The KIT receptor tyrosine kinase (CD117 antigen) is found in a variety of normal tissue cell types and in several malignant tumors, including acute myeloid leukemia. We recently encountered two tumors initially suspected as acute myeloid leukemia cutis and expressing CD117 that showed punctate positivity for cytokeratin 20 diagnostic for Merkel cell carcinoma. We evaluated 20 additional cases of MCC and found that 21 of 22 tumors (95%) expressed CD117. Intensity of CD117 expression did not appear to correlate with aggressive behavior. While the function of the KIT receptor in MCC is not known, its pathogenic role in other malignant neoplasms suggests the possibility of a similar role in MCC.

Immunostaining for cytokeratin 20 improves detection of micrometastatic Merkel cell carcinoma in sentinel lymph nodes.

BACKGROUND: Sentinel lymph node biopsy (SLNBx) can identify Merkel cell carcinoma (MCC) micrometastasis. OBJECTIVE: We attempted to examine the effectiveness of immunostaining and identify antibodies most appropriate for evaluation of SLNBxs for MCC. METHODS: Histopathologic material from 10 patients with MCC who had SLNBx was reviewed. RESULTS: Twenty-three SLNBxs from 10 patients appeared tumor-free in routine hematoxylin-eosin (H&E)-stained sections. However, tumor cells were detected in immunostained sections from 5 (22%) of 23 SLNBxs in 4 (40%) of 10 patients. Immunostains with pancytokeratin (panCK), cytokeratin-20 (CK-20), neurofilament protein, and chromogranin A were used for all primary and SLNBx specimens. All 5 (100%) micrometastatic foci stained strongly for CK-20 and panCK. Background normal lymph node tissue also stained for panCK but not for CK-20. CONCLUSION: Examination of H&E sections alone is insufficient for excluding micrometastatic MCC in sentinel lymph nodes. We observed the greatest sensitivity and specificity with anti-CK-20 antibody in identifying micrometastatic MCC in sentinel lymph nodes.

Interstitial mycosis fungoides, a variant of mycosis fungoides resembling granuloma annulare and inflammatory morphea.

BACKGROUND: Interstitial mycosis fungoides (IMF) is a rare variant of mycosis fungoides that resembles the interstitial form of granuloma annulare and inflammatory morphea. IMF has received little attention in the literature. METHODS: Clinical, histological, immunophenotypical, and genotypical findings of five cases of IMF were reviewed. The histological and immunophenotypical findings were compared with those of eight cases of interstitial granuloma annulare and six cases of inflammatory morphea. RESULTS: Five patients with IMF presented with non-indurated, erythematous macules; ill-defined erythematous plaques with slight scale; and nodules on the trunk and proximal limbs. Two of five patients had a prior diagnosis of mycosis fungoides. Skin biopsies revealed a striking dermal interstitial infiltrate of lymphocytes with rare histiocytes that resembled the interstitial form of granuloma annulare or inflammatory morphea. Epidermotropic lymphocytes were present at least focally in all cases. A band-like lymphocytic infiltrate was observed in two of five cases. In contrast, many plasma cells and histiocytes were observed in cases of inflammatory morphea and interstitial granuloma annulare, respectively. With Movat-pentachrome stains, increased dermal mucin deposition was observed in two of five IMF cases, in all cases of interstitial granuloma annulare, and in one of six cases of inflammatory morphea. There was focal loss of elastic fibers in all cases of inflammatory morphea. Immunohistochemical studies of IMF highlighted a dominant population of T cells (CD3+) in the dermis and epidermis. In contrast, moderate numbers of B cells (CD20+) were admixed with T cells and plasma cells in inflammatory morphea. Almost equal numbers of histiocytes (CD68+) and T cells comprised the infiltrate of interstitial granuloma annulare. In two of five IMF cases, a clonal T-cell population was detected by PCR T-cell gamma gene rearrangement analysis. CONCLUSION: Mycosis fungoides occasionally presents as an interstitial lymphocytic infiltrate that mimics granuloma annulare and inflammatory morphea. Hematoxylin & eosin (H&E) findings alone can sometimes distinguish the three disorders. Immunophenotyping and genotyping may be helpful in difficult cases.