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Paraneoplastic granulomatous disease occurs in approximately 7.3% of patients with non-Hodgkin lymphoma, most commonly among patients with chronic lymphocytic leukemia (CLL). These lesions are often reported to appear similar to sarcoidosis in clinical presentation and under light microscopy. However, comprehensive descriptions of the cytomorphologic characteristics of these paraneoplastic granulomas are lacking, and the mechanisms involved in their formation remain ill-defined. Noninfectious dermal granulomatous reactions have also been reported in many primary immunodeficiencies, including common variable immune deficiency and ataxia-telangiectasia. We present a case of noninfectious CD8+ predominant granulomatous dermatitis with ocular involvement occurring in the setting of CLL and marked hypogammaglobulinemia. Based on the analysis of shared factors in patients with primary immunodeficiencies and CLL, we conclude that the presence of pan-humoral immunodeficiency could itself be a risk factor for developing a CD8+ lymphogranulomatous reaction. This report and associated discussion evince that CD8+ predominant granulomatous reactions, distinct from sarcoidosis, may represent a previously unappreciated segment of the paraneoplastic granulomas observed in hematologic malignancies.

Primary systemic amyloidosis has a varied clinical presentation, making it one of the great masqueraders of other disease entities in clinical medicine. The association of amyloidosis with alopecia is uncommon with at least 22 cases reported in the literature mostly in the setting of systemic amyloidosis. Alopecia in these patients occurs either as the initial presentation of the systemic amyloidosis or it happens during the disease course. The occurrence of amyloid alopecia associated with light chain (LC) restricted plasmacytic infiltrates in the absence of systemic amyloidosis, however, it is not well known. We report 3 cases of LC-associated amyloidosis presenting with alopecia, whereby there was evidence of a systemic plasma cell dyscrasia in 2 of the patients, one of whom developed multiple myeloma. None of the patients had systemic amyloidosis. Skin presentation in the patient with multiple myeloma was characterized by a diffuse form of alopecia affecting the entire scalp, eyebrow, and axillary and pubic hair in contrast to the localized form of alopecia noted in the other 2 patients. The mechanism by which LC-associated amyloidosis eventuates in this pattern of nonscarring alopecia potentially reflects the affinity of this form of amyloid for dermatan sulfate. Dermatan sulfate is found at highest concentrations within the adventitial dermis of the superficial to mid isthmic portions of the anagen hair follicles likely interfering with the hair cycle and induces early hair follicle involution. The result is a pattern of alopecia that can clinically and to some extent pathologically resemble either androgenetic alopecia or alopecia areata.

Spontaneous hair repigmentation of physiologically white or gray hair is a rare occurrence that may be associated with melanoma in elderly individuals. We present the first case of this phenomenon in a man. A gray-haired, 80-year-old man presented to dermatology clinic with a 3-cm lock of black hair on his vertex scalp that developed over 1 year. Punch biopsies showed an increase in junctional dendritic melanocytes with rare pagetoid cells and extension along the follicular outer root sheath epithelium and interfollicular epidermis, associated with prominent dendritic melanocytic hyperplasia and pigment-containing melanocytes within the hair bulbs. Although the findings on the biopsies were not diagnostic of melanoma in situ, an irregular interfollicular distribution of melanocytes was concerning for an adjacent atypical process. A complete excision was performed and revealed melanoma in situ, lentigo maligna type. Rare reports describe spontaneous hair repigmentation as a harbinger of lentigo maligna in women. Repigmentation can occur in the setting of proliferation of malignant pigment-producing melanocytes or by paracrine stimulation of benign bulbar melanocytes through receptor tyrosine kinase KIT activation. Presence of prominent dendritic melanocytic hyperplasia and pigment-containing melanocytes within the hair bulbs in our patient's biopsies was suggestive of paracrine or physiologic stimulation of bulbar melanocytes. Given the importance of early melanoma detection and the low visibility of the scalp, this report raises awareness of an extraordinary presentation of lentigo maligna and exemplifies the importance of close clinicopathologic correlation to ensure optimal clinical management and patient outcome.

A rare variant of the eccrine spiradenoma, the giant vascular eccrine spiradenoma, has been characterized as a large circumscribed and sometimes hemorrhagic solitary tumor occurring in adults older than 50 years. Histopathologically, the lesion is comprised of distinct cell populations and cystic hemorrhagic glandular spaces. We present a 68-year-old Bengali man with a giant vascular eccrine spiradenoma and describe immunohistochemical features of this tumor. In addition, we highlight unique aspects of this case, including a rich myoepithelial component and focal pseudocapsular infiltration.

Hypertrophic discoid lupus erythematosus can resemble keratoacanthoma histomorphologically. We describe a unique case of eruptive keratoacanthomatous scaly papules in a 56-year-old woman with discoid lupus erythematosus. We review the literature and conclude by discussing important histologic features and useful immunostains to consider when attempting to discern the underlying identity and pathogenicity of such lesions.

Lymphomatoid drug reactions are atypical T cell cutaneous lymphocytic infiltrates induced by pharmacological therapy. Due to phenotypic abnormalities, clonality, and their close clinical and morphologic resemblance to T cell lymphomas, these eruptions have been categorized as drug-associated reversible granulomatous T cell dyscrasias.A total of 20 cases were encountered in which a diagnosis of CD30 lymphomatoid drug reaction was rendered.There were 11 women and 9 men ranging from 31 to 86 years of age presenting with a sudden onset often generalized cutaneous papular eruption. Two patients had vasculitic lesions. In all cases, a positive drug history was elicited and in most the initiation of the drug was temporally associated with the cutaneous eruption. Among the implicated drugs were statins (6 cases), immunomodulators (4 cases), ACE inhibitors (3 cases), antibiotics (3 cases), chemotherapy agents (3 cases), and antidepressants (1 case). Biopsies demonstrated a similar morphology, namely a superficial angiocentric lymphocytic infiltrate containing many immunoblasts. Tissue eosinophilia, interface dermatitis, and supervening eczematous changes in the overlying epidermis were observed in most cases. In all cases, the angiocentric infiltrate was highlighted by CD3, CD30, and CD4. Cytotoxic protein granule expression or monoclonality was not observed. In all cases, there was improvement or complete regression of the eruption upon drug modulation.The CD30 positive lymphomatoid angiocentric drug reaction poses a diagnostic challenge because of its close resemblance to type A lymphomatoid papulosis and potential confusion with a peripheral T cell lymphoma with large cell transformation.

Primary cutaneous follicular helper T-cell (Tfh) lymphoma is a recently described variant of peripheral T-cell lymphoma-not otherwise specified. This particular variant, usually presenting as a sudden onset of multiple plaques and nodules, is characterized by tumoral atypical T cells that express an array of Tfh markers, such as inducible T-cell costimulator, Bcl-6, CXCL13, PD-1, and CD10. The authors now present 3 patients whose known clinical skin findings are consistent with PTCL of Tfh origin (PTCL-Tfh). The typically protracted pattern of skin disease manifesting as scaly patches and plaques encountered in mycosis fungoides was not seen in our 3 cases, and there were distinguishing light microscopic and phenotypic features. These cases are similar to the few previous reported cases of PTCL-Tfh, although systemic involvement was not seen. The categorization of additional patients into this PTCL subtype in the medical literature would be needed to further characterize this new entity and may lead to better targeted treatments based on specific T-cell subtypes.

Lipophagic panniculitis of childhood is a rare condition notable clinically for an inflammatory panniculitis followed by the development of permanent lipoatrophy. In this regard, the term lipoatrophic panniculitis has been used synonymously with lipophagic panniculitis. Additional designations include lipophagic lipoatrophic panniculitis and annular lipoatrophic panniculitis of the ankles. Although lipophagic panniculitis has been associated with a number of autoimmune phenomena, a paucity of reports and limited pathological analyses to date renders this disease an elusive one whose pathogenesis is not yet established. We describe the clinical, histopathologic, and immunohistochemical findings in a case of lipophagic panniculitis of childhood in a 7-year-old boy and present it in the context of a comprehensive review of the literature. Furthermore, we offer a hypothesis regarding the pathogenetic basis of lipophagic panniculitis of childhood, suggesting cellular immunity targeting the adipocyte at the crux of its pathogenesis.

Background The cutaneous manifestations of herpes infection are primarily in the context of active infection and of the post-herpetic zosteriform eruption. The former manifests cytopathic alterations diagnostic of herpes. The latter includes lichen planus-like and granuloma annulare-like eruptions and lymphocytoma cutis. Methods We encountered skin biopsies from 28 patients whose acute or chronic herpetic or post-herpetic zosteriform lesions manifested folliculocentricity. The clinical appearance of the lesions was correlated with the histopathologic and immunohistochemical features of paraffin-embedded skin biopsies to determine the specific viral etiology. A history of underlying medical disease was noted if present. Results There were 16 men and 12 women with a folliculocentric eruption occurring after a known herpetic eruption or manifesting cytopathic changes and/or immunohistochemical findings compatible with herpes virus in lesional skin biopsies. Underlying immune dysregulatory states were present in most cases, namely, malignancy, anticonvulsant or antidepressant therapy, diabetes mellitus, psoriasis, Crohn disease, and other conditions. All biopsies demonstrated dense lymphohistiocytic infiltrates in or around hair follicles with variable necrosis, while active infections also showed cytopathic and/or immunohistochemical evidence of herpetic alterations, most commonly varicella zoster. Other features included interfollicular interface dermatitis, lymphocytic eccrine hidradenitis, neuritis, and folliculocentric vasculitis. Conclusions Cutaneous herpetic eruptions can evoke a predominantly folliculocentric mononuclear cell reaction and vasculitis; there is an association with underlying endogenous and/or iatrogenic immune dysregulation. Most cases are secondary to reactivation of varicella zoster. The histomorphology suggests a role for cell-mediated immunity. Antigenic homology of an endogenous 72-kd heat shock protein in follicles with that of a herpetic heat shock protein, in concert with an intrafollicular proliferative response of γ-δ T lymphocytes, may explain the follicular localization and composition of the infiltrate.

Hodgkin lymphoma (HL), although a common hematopoietic malignancy, presents as a primary cutaneous form in extraordinarily rare instances. In this study, we present a remarkable case of a 76-year-old woman with a history of bony metastatic breast cancer who developed multiple subcutaneous nodules on the left neck and scalp. A biopsy revealed the histological and immunohistochemical findings of classic HL. She was treated with systemic chemotherapy and quickly achieved disease remission. Five months later, she was alive and without evidence of lymphoma, consistent with our understanding of primary cutaneous HL as an indolent variant of HL.

Aggressive extracutaneous B-cell lymphomas span the various stages of B-cell ontogeny and include B-cell lymphoblastic lymphoma, Burkitt lymphoma, mantle cell lymphoma, and diffuse large B-cell lymphoma. Diffuse large B-cell lymphomas represent the most common histologic subtype of non-Hodgkin lymphomas, comprising 30% of adult non-Hodgkin lymphomas in the United States. A distinctive form of diffuse large B-cell lymphoma is the double-hit lymphoma, with most cases exhibiting a combined MYC and BCL2 rearrangement, leading some hematopathologists to propose the term MYC/BCL2 lymphoma. More recently, MYC rearrangement with multiple copies/gain of BCL2 or multiple copies/gain of MYC with a BCL2 rearrangement have been described and exhibit a very similar clinical course to conventional double-hit lymphomas. We report the seventh case of diffuse large B-cell lymphoma exhibiting this distinct cytogenetic abnormality and the first reported case in the skin. The patient's clinical course was aggressive, succumbing to disease 18 months after his initial presentation.

A 70-year-old white man with stage C chronic lymphocytic leukemia who was being successfully treated with ibrutinib and rituximab developed bilateral, purpuric, painful cutaneous nodules. Biopsies of these nodules did not reveal the usual Th2 milieu of chronic lymphocytic leukemia but instead exhibited a Th1-rich lymphocytic infiltrate with resultant neutrophil and granulomatous inflammation. The eruption resolved with drug cessation emphasizing the potential importance of this drug in treating conditions associated with Th2 dysregulation.

Posttransplant lymphoproliferative disorders define an important form of lymphoproliferative disease causally linked with a state of iatrogenic immune dysregulation inherent to the posttransplant setting. Most posttransplant lymphoproliferative disorders are in the context of Epstein-Barr virus-associated B-cell lymphoproliferative disease, most notably diffuse large-cell B-cell lymphoma. A less common variant falls under the rubric of posttransplant T-cell lymphoproliferative disease, which is largely unrelated to Epstein-Barr virus infection. Anaplastic large-cell lymphoma (ALCL) is the most recognized form of posttransplant T-cell lymphoproliferative disease. Although the 6p25.3 translocation is seen in a variety of B-cell lymphoproliferative disorders, this particular translocation in the spectrum of T-cell lymphoproliferative disease is a fairly specific finding pointing toward a diagnosis of primary cutaneous ALCL and a rare subset of lymphomatoid papulosis. This translocation in the peripheral T-cell lymphoma setting serves as a favorable prognostic predictor. We report a case of an 81-year-old heart transplant recipient who developed an expansile neck mass 17 years after his heart transplant. A diagnosis of cutaneous ALCL was subsequently made with cytogenetic analysis yielding the 6p25.3 translocation. The characteristic biphasic morphology of a small-cell epidermotropic neoplastic cell populace in concert with a dermal based large-cell infiltrate characteristic for those cases of ALCL harboring this translocation was seen. After excision of the nodule, his azathioprine was withheld. He is currently alive and well without evidence of disease.

Epidermotropic B-cell lymphoma is a very rare entity that has primarily been reported in the literature as anecdotal case reports. The majority of the reported cases exhibit a diffuse skin rash affecting middle-aged to older adults with a male predominance. The exact mechanism of marginal zone B-cell localization to the epidermis is unclear.To describe a very rare subset of cutaneous B-cell lymphoma and explore potential pathogenetic mechanisms for the epidermotropic tendency, the hospital database and literature review was conducted to isolate cases of epidermotropic B-cell lymphoma. Routine hematoxylin and eosin stain followed by selective phenotypic studies.Two of the cases were encountered in the hospital database, whereas 5 cases have been previously reported; material was requested on previously reported cases and was received on 3 of them. In one of the 2 cases encountered in our database, the patient presented with a progressive skin rash over 7 months resembling pityriasis rosea. Subsequent to a diagnosis of B-cell lymphoma, further staging revealed bone marrow involvement. The other patient, an elderly female, presented with isolated nodules. The biopsies of both cases showed areas of superficial band-like lymphocytic infiltration with large monocytoid appearance and an epidermotropic pattern of lymphocyte migration into the epidermis. Neoplastic cells were extensively positive for CD20, CD79a, and BCL-2 and negative for CD10 and BCL-6. Of interest, a similar pityriasis rosea-like presentation was encountered in the cases reported in the literature. All patients were elderly males with established bone marrow, peripheral blood, and spleen involvement several months to years after the initial cutaneous presentation in 3 of them. None of the patients to date have died of lymphoma. CXCR3 epidermotropic B cells were detected in both our cases and in 3 of the 3 previously published cases.Epidermotropic B-cell lymphoma represents a subset of marginal zone lymphoma characterized by a papulosquamous rash most frequently resembling pityriasis rosea, occurring almost exclusively in older males. We speculate that aberrant expression of CXCR3 in marginal zone lymphoma of the skin is associated with migration of lymphoma cells to the epidermis and could lead to an epidermotropic pattern given the known role of CXCR3 expression in neoplastic T cells in the localization of mycosis fungoides to the epidermis. There is a tendency toward bone marrow, spleen, and peripheral blood involvement.

Central nervous system involvement by mycosis fungoides (MF) is rare and is usually seen in advanced stages of the disease. We describe a patient with early-stage follicular MF who presented with changes in mental status. Despite an initial diagnosis of vasculitis based on clinical and brain biopsy results, the postmortem examination revealed extensive infiltration of MF cells throughout the brain with leptomeningeal involvement. This case in addition to the accompanied review of literature illustrates the importance of the awareness of central nervous system involvement by MF and highlights the need for an urgent neurologic evaluation in patients with a history of MF now presenting with neurologic signs or symptoms.

Primary cutaneous anaplastic large cell lymphoma (ALCL), similar to systemic ALCL, has as its histomorphologic hallmarks cohesive sheets of large lymphoid cells expressing CD30. Several morphologic variants of systemic ALCL have been reported, including the common (classic) type, lymphohistiocytic, and small cell variants. The small cell variant of ALCL is characterized by a predominant cytomorphology which is unexpected for ALCL, being in the context of a small- to medium-sized hyperchromatic atypical lymphocyte. Although well recognized in its systemic form including cases with secondary cutaneous involvement, it is less well characterized as a form of primary cutaneous ALCL. In this study, we collected 8 cases of primary cutaneous small cell variant of ALCL and examined their clinical, histologic, and phenotypic features. All patients were middle aged to older adult men; the youngest patient was a 46-year-old man with underlying hepatitis C. In one case, there was a history of lymphomatoid papulosis. In all patients, the disease was in the context of a local regional presentation. Patients were treated with complete excision and/or radiation except in one in whom chemotherapy was administered. In all but one patient, the cutaneous presentation was a regionally confined process; however, in 2 cases, recurrent disease occurred, and in 25% of cases, extracutaneous dissemination specifically to regional lymph nodes was observed. Although there was nodal involvement, there was no dissemination to bone marrow or peripheral blood; no patient has died because of disseminated lymphoma. In all cases, there was a predominance of small atypical hyperchromatic cells with a variable background of larger hallmark cells typical of ALCL. Epidermotropism was seen in half of the cases, and in one case, there was striking pseudoepitheliomatous hyperplasia. The smaller cells demonstrated CD30 positivity, and the neoplastic cells showed a CD4-positive phenotype with a variable expression of cytotoxic proteins in about half of the cases, whereas in the remaining cases, a double negative phenotype was observed. Epithelial membrane antigen expression was observed in the cases tested. In our literature review, similar demographics were observed with a comparable percent of cases with extracutaneous dissemination; one case manifested an aggressive clinical course eventuating in death. In summation, the small cell variant of primary cutaneous ALCL exhibits distinctive features clinically and histologically. While exhibiting an overall higher incidence of extracutaneous dissemination, the prognosis fairs better compared with other forms of cutaneous T-cell lymphoma associated with extracutaneous dissemination, an event that defines a harbinger of aggressive disease.

In 2007, Petrella et al described a series of patients with clonally restricted, well-differentiated, nonepidermotropic, CD8-dominant lymphocytic infiltrates localized to the facial area. The clinical course described was indolent. A CD8 variant of primary cutaneous pleomorphic T-cell lymphoma has been proposed; however, there are many dissimilar features. The authors encountered 2 patients with CD8⁺ indolent lymphoid proliferation of the face, localized to the eyelid. Both patients were males in their 30s presenting with localized lesions of the eyelids. The biopsies showed an effacing lymphocytic infiltrate that spanned the sampled dermis. The lymphocytes were well differentiated, exhibiting mild nuclear contour irregularity. The infiltrate was predominated by CD8⁺ lymphocytes demonstrating TIA expression. There was a minimal B-cell component in 1 case, whereas another showed a significant degree of B-cell hyperplasia. They both underwent complete excision without recurrence. CD8⁺ indolent lymphoid proliferation has a reproducible clinical and morphologic presentation that warrants categorization as a distinct form of indolent lymphoproliferative disease, preferentially involving older adults with the most common site being the ear, recognizing that the nose, acral surfaces, and eyelids can also be involved.

Mycosis fungoides (MF) is the most common of the family of cutaneous T-cell lymphomas, accounting for 65% of all cases of cutaneous T-cell lymphomas. The classic phenotypic profile is one defined by CD4+ T cells showing a reduction in the expression of CD7 and CD62L. There are 3 previous reports describing CD20 expression in MF. The cell surface antigen CD20 is a transmembrane glycosylated phosphoprotein expressed in the early stages of B-cell development before differentiation into plasma cells. Two male patients, aged 14 and 44 years, presented with persistent truncal plaques up to 8 cm of 1 and 4 years duration, respectively. A third patient, an 80-year-old female, presented with a 1-year history of progressive nodules involving the head and neck area. Cases 1 and 2 both responded to topical treatment modalities. The biopsies in cases 1 and 2 showed features typical of plaque stage MF, whereas case 3 was compatible with follicular MF with tumor stage transformation. Phenotypically, the aberrant cell populace demonstrated a CD4+, CD7-, and CD62L- phenotype; at variance with classic MF was the expression of CD20. Although there were a few PAX5-positive staining cells, definitive colocalization studies were negative. Other B-cell markers and heavy chain immunoglobulin rearrangement were not detected. There are a growing number of reports describing T-cell lymphomas and leukemias with CD20 expression. Of the 6 CD20+ MF cases reported in the literature to date, 3 have been associated with a more aggressive clinical course; all but one case have occurred in males.

Cocaine-associated retiform purpura is a recently described entity characterized by striking hemorrhagic necrosis involving areas of skin associated with administration of cocaine. Levamisole, an adulterant in cocaine, has been suggested as the main culprit pathogenetically. Four cases of cocaine-associated retiform purpura were encountered in the dermatopathology practice of C. M. Magro. The light microscopic findings were correlated with immunohistochemical and immunofluorescence studies. All 4 cases showed a very striking thrombotic diathesis associated with intravascular macrophage accumulation. Necrotizing vasculitis was noted in 1 case. Striking intercellular adhesion molecule-1 (ICAM-1)/CD54 expression in vessel wall along with endothelial expression of caspase 3 and extensive vascular C5b-9 deposition was observed in all biopsies examined. Cocaine-induced retiform purpura is a C5b-9-mediated microvascular injury associated with enhanced apoptosis and prominent vascular expression of ICAM-1, all of which have been shown in prior in vitro and in vivo murine models to be a direct effect of cocaine metabolic products. Antineutrophilic cytoplasmic antibody and antiphospholipid antibodies are likely the direct sequelae of the proapoptotic microenvironment. The inflammatory vasculitic lesion could reflect the downstream end point reflective of enhanced ICAM-1 expression and the development of antineutrophilic cytoplasmic antibody. Levamisole likely works synergistically with cocaine in the propagation of this syndromic complex.

Introduction: Blastic transformation (BT) of marginal zone lymphoma or mucosa-associated lymphoid tissue lymphoma has been mainly reported in the spleen and stomach. Primary cutaneous marginal zone lymphoma that undergoes BT is rare and not well documented. We describe 8 patients with blastic primary cutaneous marginal zone lymphoma and compare the clinical, pathologic, and molecular findings of these patients with 10 cases previously reported in the literature. Results: The cases of blastic marginal zone lymphoma could be categorized into cases of de novo blastic marginal zone lymphoma and large-cell transformation arising in a background of a history of biopsy proven marginal zone lymphoma. The cases of de novo blastic marginal zone lymphoma occurred in elderly patients without any medical history. In each of the cases, the lesions were radiated, not treated, or treated with complete excision without any death due to lymphoma nor was there any evidence of extracutaneous dissemination. Large-cell transformation arising in background of marginal zone lymphoma typically occurred in patients who were younger; 2 of the 4 cases were immunocompromised. The clinical course in each of the cases was aggressive with 3 of the 4 patients succumbing to disseminated disease while 1 patient developed extracutaneous nodal disease. Phenotypically, there was an expression of CD5 in a total of 3 of the 8 cases and CD23 in 3 of the 8 cases. Commonality of B-cell clones was demonstrated in 2 cases where biopsies were available of both the less aggressive appearing marginal zone lymphoma and the transformed biopsies. Cytogenetic abnormalities associated with BT included a deletion of chromosome 7q in all cases tested. Conclusion: Large-cell transformation arising in a patient with a history of marginal zone lymphoma portends a worse prognosis, including death from disseminated disease, whereas a de novo presentation of blastic marginal zone lymphoma may define a clinical course similar to other forms of low-grade cutaneous B-cell lymphoma. The expression of CD5 and CD23 may define a phenotypic profile associated with BT. It is possible that marginal zone lymphomas associated with CD5 and CD23 positivity should be followed more closely and/or treated with radiation and/or complete excision.

Diffuse large cell B-cell lymphoma of the skin is most commonly represented by diffuse large cell variants of primary cutaneous follicle center lymphoma and the leg-type lymphoma. In a minority of cases, the infiltrates are an expression of stage 4 disease of established extracutaneous B-cell lymphoma. We describe 1 female patient 85 years of age with an aggressive form of primary cutaneous B-cell lymphoma manifesting in multiple firm erythematous indurated solid nodules 1-2 cm each symmetrically on the face periorbitally and on the upper extremities bilaterally. The tumor was a de novo presentation of this aggressive form of lymphoma. The disease demonstrated an aggressive course with only transient improvement of skin lesions after chemotherapy. Punch biopsy taken from a left arm skin lesion showed a diffuse and nodular large cell lymphocytic infiltrate in the 15-20 μm range exhibiting round to oval nuclei and prominent eosinophilic nucleoli. Phenotypically, the tumor cells were CD10, Bcl-2, Bcl-6, and CD43 positive with a residuum of a follicular dendritic cell network revealed by CD21 staining. There was c-MYC rearrangement and CDKN2A deletion in this sample. The importance in reporting this case is to emphasize that in the context of primary cutaneous B-cell lymphoma, the 9p21 deletion while characteristic of the leg-type lymphoma is not a unique signature of the leg-type lymphoma and is not exclusionary to lymphomas falling under the designation of follicle center lymphoma. As with the leg-type lymphoma, however, this cytogenetic abnormality is a critical determinant to a more aggressive clinical course.

Adult T-cell leukemia/lymphoma (ATLL) is a rare and often aggressive lymphoid malignancy known to be associated with human T-cell lymphotropic virus type 1. There are 2 broad categories: acute and chronic. In the acute category, there is a leukemic and a lymphomatous variant, whereas in the designated "chronic" form, there is mild peripheral blood lymphocytosis. The intermediate "smoldering" category is without peripheral blood lymphocytosis with only discernible skin involvement. We present a 68-year-old human T-cell lymphotropic virus type 1 seropositive female with a mild peripheral blood atypical lymphocytosis who had indurated nodules on her hands of 2 years duration and a new scaly ichthyosiform eruption on her lower extremities. Histopathologic examination of the hand biopsy revealed coalescing nodules of large atypical noncerebriform lymphocytes with focal areas of epidermotropism. Phenotypically, the infiltrate was positive for β-F1, CD2, CD4, CD5, CD7, Foxp3, and CD25. In both biopsies, there was striking upregulation of TOX (thymocyte selection-associated high mobility group box factor) in the nuclei of neoplastic cells. The second biopsy taken from the ichthyotic patch on the patient's left leg showed a subtle pattern of epidermal infiltration by atypical noncerebriform lymphocytes and a distinct compact scale consistent with the clinical picture of ichthyosis. The histopathologic appearance was that of a yet undescribed ichthyosiform mycosis fungoides-like presentation of chronic ATLL. In addition, the observed upregulation of nuclear TOX may play an oncogenic role in ATLL. The course to date in this patient has been relatively indolent, although the patients believe that large cell transformation could portend more aggressive disease.

Epithelial sheath neuroma is a rarely recognized but established entity in the medical literature. First described in 2000 by Requena et al, there have only been 7 published cases to date, mostly in female patients and presenting as symptomatic solitary lesions on the back without a known history of trauma. In 2006, Beer et al described and reviewed a dozen cases in which epithelial sheath neuroma-like features were seen in the advent of a surgical procedure, which was termed "re-excision perineural invasion" and attributed to possible eccrine duct implantation during surgery. Our case is a 66-year-old male patient who underwent an excision of a melanocytic neoplasm in which a reactive epithelial sheath neuroma was incidentally discovered in the excision specimen, adjacent to the biopsy site cicatrix. Histologically, there was benign cutaneous nerve hyperplasia with a proliferation of squamous epithelium in intimate apposition to the nerve bundles in the superficial dermis. We postulate that the process active in the formation of re-excision perineural invasion is the same as in epithelial sheath neuroma and that minor trauma not appreciable on histologic examination is responsible in the latter entity. We performed IL-6 staining and documented that IL-6 was upregulated at the interface of the nerve and reactive epithelium, but was absent in nerves distant from the site of surgery, suggesting that IL-6 may be essential to the lesion's development. The recognition of reactive epithelial sheath neuroma including the subcategory of re-excision perineural invasion is crucial for the dermatopathologist to prevent mislabeling this reactive entity as a perineural squamous cell carcinoma, which has clinical consequences for the patient such as wider re-excision and radiation treatment. Additionally, we have identified a potential pathophysiologic basis for this lesion.