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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.

Infection by SARS-CoV-2 commonly begins in the nasopharynx, and the cytologic and molecular correlates are not characterized. Fifty-eight cytologic preps (20 oral and 38 from the nasopharynx) were obtained from ten patients and analyzed in a blinded fashion for SARS-CoV-2 spike and envelope protein by immunohistochemistry and viral RNA by in situ hybridization. qRTPCR identified three positive cases and seven controls; the three cases reported mild symptoms that resolved in 2–3 days. Blinded analyses confirmed the presence of the SARS-CoV-2 spike and envelope proteins and viral RNA in the three cases and viral absence in the seven controls. A signal for the positive cases was evident in each nasopharyngeal and none of the oral samples. Viral RNA/proteins localized exclusively to glandular cells and was present in high copy number. Blinded analysis of the cytology documented that the glandular cells infected by SARS-CoV-2 showed marked degeneration with ciliocytophthoria; viral inclusions were not evident. Co-expression analysis showed viral infected cells had increased apoptosis, marked by strong expression of activated caspase 3. Weekly serial testing of two of the cases showed persistence of productive viral infection for up to 2 weeks after symptom onset. It is concluded that the target cell of SARS-CoV-2 in the head and neck region is the glandular cell of the nasal passages, that viral infection is lytic and associated with high copy number that facilitates viral spread. The method outlines a simple, rapid test for productive SARS-CoV-2 based on immunohistochemistry or in situ hybridization of the glandular cells from the nasopharynx., Highlights • SARS-CoV-2 infects the glandular cells of the nasopharynx. • SARS-CoV-2 RNA can be detected in situ in cytology smears. • SARS-CoV-2 capsid can be detected in situ in cytology smears. • These in situ tests can be used for rapid diagnosis of COVID-19.

The vaccine BCG has been reported to offer protection against SARS-CoV-2 infection. It has been hypothesized this is based on nonspecific enhancement of innate immunity. This study addressed whether there is strong homology between a SARS-CoV-2 capsid protein and a Mycobacterium bovis protein that would allow for stronger, more specific immune protection. The study also showed the utility of immunohistochemistry in the diagnostic pathology laboratory for elucidating this information. Immunohistochemistry documented that an antibody directed against the SARS-CoV-2 envelope, but not the spike or membrane proteins, strongly cross hybridized to 11/11 Mycobacterial species tested, including M. bovis. BlastP analysis showed high homology of the SARS-CoV-2 envelope protein with 12 consecutive amino acids of the protein LytR C, which is a consensus protein unique to Mycobacteria. Six additional cases of human tuberculosis with few organisms showed that the viral envelope specific antibody (5/6) was more accurate than the AFB stain (2/6) for diagnostic purposes. These data indicate BCG vaccination induces a specific immunity against SARS CoV-2 that targets the viral envelope protein that is essential for infectivity. Thus, a concurrent booster or first use of the BCG vaccine may reduce the severity of the current COVID-19 pandemic. The data also suggests the value of using the SARS-CoV-2 envelope antibody in the diagnosis of Mycobacterial infections in formalin fixed, paraffin embedded tissues by the diagnostic pathologist., Highlights • The envelope protein of SARS-CoV2 is strongly homologous with a consensus Mycobacterial protein. • Immunohistochemistry with an antibody against the viral envelope, thus, can detect Mycobacterial infections. • This test is superior to the AFB stain for Mycobacterial detection by the anatomic pathologist. • The BCG vaccine offers a strong, viral specific immunity against COVID-19 due to this strong homology.

COVID-19, the disease caused by the novel Coronavirus, SARS-CoV-2, is increasingly being recognized as a systemic thrombotic and microvascular injury syndrome that may have its roots in complement activation. We had the opportunity to study the placental pathology of five full-term births to COVID-19 patients. All five exhibited histology indicative of fetal vascular malperfusion characterized by focal avascular villi and thrombi in larger fetal vessels. Vascular complement deposition in the placentas was not abnormal, and staining for viral RNA and viral spike protein was negative. While all cases resulted in healthy, term deliveries, these findings indicate the systemic nature of COVID-19 infection. The finding of vascular thrombosis without complement deposition may reflect the systemic nature of COVID-19's procoagulant effects unrelated to systemic complement activation., Highlights • This paper explores thrombosis in the placentas COVID-19-positive patients at our hospital • Potential prothrombotic mechanisms are explored. • Direct infection of the placentas is ruled out as a cause.

Acral pseudolymphomatous angiokeratoma of children (APACHE) and unilesional mycosis fungoides (MF) are two rare dermatoses in the pediatric population which may have overlapping clinical and histopathologic features, making differentiation between these two diagnoses difficult. We present two similar cases of a solitary plaque on the thigh of a child, one representing APACHE and the other representing unilesional MF with granulomatous features, and we provide a brief overview of the clinical and histopathologic features of APACHE and unilesional MF.

Granuloma annulare (GA) is a benign, self-limited skin disease of unknown etiology characterized by annular, flesh-colored to erythematous grouped papules or plaques. Lesions of GA are typically located on the lateral or dorsal surfaces of the hands and feet, arms, thighs, and trunk. We present the case of a patient with GA who presented with erythematous, annular plaques localized to the bilateral inguinal folds, mimicking tinea cruris. On clinical examination, the lesions were thought to be tinea cruris. A subsequent punch biopsy revealed the lesions to be granuloma annulare. This case highlights an unusual location where GA can first present in a patient. It also suggests that GA should be considered among the differential diagnoses along with tinea cruris, when evaluating localized annular lesions of the groin.

The cutaneous manifestations of Crohn's disease are myriad. A 15-year-old girl presented with recurrent lip swelling and eventual development of diarrhea and targetoid macules on the palms, feet, and back. She was finally diagnosed with Crohn's disease in the setting of a clinical presentation and histopathology consistent with orofacial granulomatosis and erythema multiforme. We review the literature and summarize reported occurrences of these cutaneous diseases in children with Crohn's disease.

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.

Histiocytoid Sweet's syndrome was originally described as cutaneous lesions of Sweet's syndrome where the infiltrate is mostly composed of histiocytoid mononuclear cells. The putative cell has been interpreted as an immature neutrophil based on the intense expression of myeloperoxidase.To better understand the nature of the infiltrate and potential mechanisms leading to this distinct form of cutaneous inflammatory cell influx, thirteen cases of histiocytoid Sweet's syndrome, encountered in the routine and consult practice of one of the authors, were studied. The clinical features and microscopic findings are summarized.The study comprised eight men and five women aged from 23 to 80. There was a significant association with underlying myeloproliferative disease. In particular, five patients had underlying myelodysplastic syndrome. One patient had unspecified chronic myeloproliferative disorder and another had AML. Two cases were triggered by drug therapy (Cox-2 inhibitors). One patient had familial Mediterranean fever. The eruption was asymptomatic and an aggressive clinical course was not observed in most cases. Skin biopsies were composed of striking angiocentric and intersititial mononuclear cell infiltrates, often accentuated in the deeper dermis and subcutaneous fat. There was marked leukocytoclasia. Neutrophils were sparce or absent. These cells were strongly positive for CD163 and either expressed CD16 or myeloperoxidase. Variable positivity for myeloid dendritic cell markers including CD11c, BDCA-3, TCL1 oncogene, MXA and CD123 was observed.The histiocytoid cells of histiocytoid Sweet's syndrome define a novel subset of activated monocytes. This variant of Sweet's syndrome has a significant association with underlying myeloproliferative disease.

A previously healthy 68-year-old male presented with a rash on his right lower leg. The lesions had spread along the leg since onset 9 days prior, and the patient reported localized soreness and pruritus. He denied systemic symptoms including fever, fatigue, myalgia, joint pain, and recent illness. Physical examination revealed a serpiginous, purpuric eruption on the anterior and posterior right thigh and lower leg. A 4mm punch biopsy from the right lower leg revealed a Th2 dominant process reflective of a type IV delayed hypersensitivity reaction. Superficial and deep angiocentric and eccrinotropic lymphocytic infiltrate and tissue eosinophilia were noted. Degranulated eosinophils forming 'flame figures' were also identified with accompanying mural edema and red blood cell extravasation. Further evaluation revealed an elevated antistreptolysin O antibody, though the remainder of the work up was unremarkable. Clinicohistopathologic correlation supported the diagnosis of Blaschkolinear purpuric Wells' Syndrome. This case highlights a unique presentation of a rare inflammatory dermatosis, and serves as a reminder that given Wells' can be associated with underlying malignancy, an age appropriate work up, based on patient history and presentation, may be warranted.pemJ Drugs Dermatol. 2017;16(10):1036-1038./em/p.

Photosensitivity, or skin sensitivity to ultraviolet radiation (UVR), is a feature of lupus erythematosus and other autoimmune and dermatologic conditions, but the mechanistic underpinnings are poorly understood. We identify a Langerhans cell (LC)–keratinocyte axis that limits UVR-induced keratinocyte apoptosis and skin injury via keratinocyte epidermal growth factor receptor (EGFR) stimulation. We show that the absence of LCs in Langerin–diphtheria toxin subunit A (DTA) mice leads to photosensitivity and that, in vitro, mouse and human LCs can directly protect keratinocytes from UVR-induced apoptosis. LCs express EGFR ligands and a disintegrin and metalloprotease 17 (ADAM17), the metalloprotease that activates EGFR ligands. Deletion of ADAM17 from LCs leads to photosensitivity, and UVR induces LC ADAM17 activation and generation of soluble active EGFR ligands, suggesting that LCs protect by providing activated EGFR ligands to keratinocytes. Photosensitive systemic lupus erythematosus (SLE) models and human SLE skin show reduced epidermal EGFR phosphorylation and LC defects, and a topical EGFR ligand reduces photosensitivity. Together, our data establish a direct tissue-protective function for LCs, reveal a mechanistic basis for photosensitivity, and suggest EGFR stimulation as a treatment for photosensitivity in lupus erythematosus and potentially other autoimmune and dermatologic conditions.

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.

Primary cutaneous CD4 + small/medium sized pleomorphic T-cell lymphoma (SMPTCL) is unique among the peripheral T-cell lymphomas because of its indolent nature, typically presenting as a solitary nodule or plaque in the head and neck area of middle-aged and older adults. Recent studies have suggested a follicular helper cell origin for these lesions. Materials and methods A retrospective review was conducted on all cases of SMPTCL diagnosed between 2008 and 2017. The goal of our study was to better categorize the clinical, pathologic and molecular features of cases of SMPTCL showing a significant degree of CD30 neoplastic large cell infiltration. Results Fifteen patients (10 male, 5 female) were encountered (age 33–86 years at presentation). All lesions were solitary and the head and neck region was the most common area of involvement (7 cases). Surgical excision alone was performed in 6 cases and was supplemented with radiation in 5 cases. Disease recurrence did not occur. Spontaneous regression following biopsy was reported and two patients had a history compatible with lymphomatoid papulosis. All cases showed pathologic features characteristic of SMPTCL. Additionally, there were many larger CD30 + T-cells occupying 15–30% of the infiltrate. Monoclonality was demonstrated in 5 of 10 cases in which clonality studies were performed. Conclusion CD30 positivity amidst large neoplastic T-cells is not uncommon in SMPTCL. The extent of CD30 positivity in SMPTCL needs to be defined further along with its association with other forms of CD30 + lymphoproliferative disease including its potential categorization as a form of endogenous CD30 + lymphoproliferative disease.

The authors address the entity of cutaneous lymphadenoma. Although considered benign, cutaneous lymphadenoma can be easily misdiagnosed as basal cell carcinoma because of its close clinical and histological resemblance. This entity is rare and controversial both in terms of its histogenesis and the various diagnostic terms assigned to it throughout the literature. While rare, cutaneous lymphadenoma should be considered in the differential of any facial nodule or papule in addition to the more common basal cell carcinoma, nevi, cysts, and appendiceal tumors.

Background Atrophic papulosis is a rare thrombo-occlusive disease, characterized by the appearance of multiple atrophic porcelain-white skin papules, with a surrounding erythematous rim, which are histologically consisting of wedge-shaped necrosis of the dermis. Objective It consists of two variants: (i) the benign atrophic papulosis (BAP) only involving the skin and (ii) the malignant atrophic papulosis (MAP) also involving several internal organs with a cumulative five-year survival rate of approx. 55%. While the probability of only having a BAP at onset is approximately 70%, increasing to 97% after 7 years of monosymptomatic cutaneous course, no close long-term follow-up of the development of the skin lesions has been reported. Methods We present a precise visual documentation of the evolution of the disseminated skin lesions in a female patient with BAP spanning over two decades. Results A considerable improvement and/or clinical resolution of the majority of the lesions disputing the scarring character of the atrophic porcelain-white skin papules has been detected. Conclusion BAP not only exhibits an excellent prognosis, but resolution of lesions can also occur after a considerable period of time.

Sclerosing mediastinitis (SM) is an aggressive fibroproliferative process in the mediastinum that may lead to encasement of mediastinal structures within a dense fibrotic mass. This disease may cause significant clinical complications, morbidity, and even mortality. The etiology and pathogenesis of SM is unclear and in more than one third of cases remains idiopathic. Among the known causes of SM, granulomatous infection is the commonest. Association of SM with radiation therapy has been rarely reported. Herein, we are reporting a case of postradiation sclerosing mediastinitis diagnosed in fine needle aspiration (FNA) specimen. To our knowledge, this is the first reported case of postradiation sclerosing mediastinitis with unusual striking intracytoplasmic glycogen accumulation. Having high index of suspicion and awareness of the fact that this entity may be also associated with radiation therapy, will be helpful in avoiding diagnostic pitfalls in FNA specimens and guiding proper clinical management.

Angiolymphoid hyperplasia with eosinophilia (ALHE) is a distinctive lymphocyte rich vasoformative proliferation comprising epithelioid-appearing endothelial cells with partially canalized capillary vessels in a lymphohistiocytic and eosinophil rich environment. ALHE presents clinically as single or multiple pink-brown dome-shaped papules or nodules, most commonly on the ear and peri-auricular area, followed by the face, and scalp. ALHE involving the subungual unit is rare with only 5 previously reported cases and all involved the underlying bone. The authors describe a case of a painful subungual nodule of the left 1st fingernail in a 48-year-old woman. An excisional biopsy was performed confirming a diagnosis of ALHE. There was no bone involvement and immediately following excision of the tumor, there was complete resolution of her symptoms. Our patient’s presentation expands upon the clinical and histopathological spectrum of subungual ALHE.

Author(s): Magro, Cynthia; Guo, Ruifeng; Nguyen, Giang Huong; Tsang, Hamilton; Momtahen, Shabnam | Abstract: Background: Lymphomatoid drug reactions can mimic endogenous T and B cell lymphoproliferative diseases.Objectives: We present a novel form of cutaneous drug reaction with features of pityriasis lichenoides (PL), a recognized form of T cell dyscrasia. Methods: Ten cases were studied where a cutaneous eruption exhibiting semblance to PL within a few weeks to months after starting a particular drug. Results: The patient cohort comprised 7 females and 3 males with the mean age of 60 years. Widely distributederythematous cutaneous lesions were present in 6 cases whereas a more localized distribution was seen in three cases. The most frequently implicated drugsassociated with the eruption were antidepressants and statins. Histologic examination showed a morphologic picture identical to PL including marked epitheliotropism of mildly atypical lymphocytes, psoriasiform epidermal hyperplasia, dyskeratosis, hemorrhage, and a thick parakeratotic scale. Therewas a significant reduction in the expression of CD7 and CD62L amid the T cells. Regression of the eruption occurred in all cases excluding one. Conclusion: Thefindings conform the categorization of this process as a form of T-cell dyscrasia albeit one that is reversible, dependent on the drug withdrawal. The limitationof our study includes the retrospective design of the study.

Pustular psoriasis occurs rarely in children but can present with acute toxicity requiring inpatient admission. For the best approach, medical providers should have an evidence based and systematic treatment algorithm in their armamentarium. Toillustrate this point, we describe a 13-year-old girl who was admitted with generalized pustular psoriasis and who responded dramatically to "wet wrap" therapy and cyclosporine bridged to etanercept. Using this case example, we highlight the three most important considerations in any patient with new onset pustularpsoriasis: avoidance of disease complications, acute "rescue" therapy, and maintenance therapy.

Bowel-associated dermatosis - arthritis syndrome (BADAS) is a neutrophilic dermatosis characterized by cutaneous lesions that begin as erythematous macules and progress to vesiculopustular eruptions. It has been described in patients with inflammatory bowel disease as well as those who have undergone various intestinal surgeries. Pathologically, the lesions show features of vasculitis without fibrinoid necrosis. In a patient with diagnosed inflammatory bowel disease, these neutrophilic dermatoses should be viewed as external signals of bowel inflammation. Management requires long-term treatment of the underlying disease. We report a case of BADAS in a patient with ulcerative colitis in which the skin lesions were associated with increased colonic inflammation.

Deep penetrating nevi (DPN) are a relatively uncommon subtype of melanocytic nevi. A small subset of these lesions exhibit atypical features (cytologic and architectural atypia, mitotic activity) seen in melanoma. These lesions we term the deep penetrating nevuslike borderline tumor. Unequivocal melanomas can show overlapping morphologic features of DPN, which have been termed plexiform melanomas. 40 cases of DPN-like borderline tumor were identified along with 6 cases of plexiform melanoma. Clinical follow up was obtained, along with cytogenetic analysis in the form of fluorescent in situ hybridization (FISH) and/or comparative genomic hybridization (CGH). The DPN-like borderline tumor cases included 24 females and 16 males. Of sentinel lymph node biopsies performed, 1/3 of cases showed lymph node involvement. All patients where an aggressive clinical approach was adopted remain free of disease. All 6 DPN-like borderline tumor cases tested by CGH showed normal cytogenetics, as did 7 of 9 cases tested by FISH. Of the plexiform melanomas, 4/6 patients died of disease. In 3 cases there was morphologic progression from a DPN-like borderline tumor to overt melanoma. In one case of progression, cytogenetics was normal in the DPN-like borderline tumor and then abnormal in the progressed melanoma. DPN-like borderline tumors are melanocytic tumors associated with a high incidence of regional lymph node disease and exhibiting the potential for melanoma progression despite a normal cytogenetic profile. Patients with these lesions should be aggressively managed, with at least complete re-excision and consideration of sentinel node biopsy, regardless of cytogenetic data.

Key Clinical Message It's important to assess cases both clinically and pathologically for factors potentially predictive of an aggressive clinical course. We concluded that the relative immunosuppressive effects of PD1 may contribute to tumor progression while the lack of staining for cutaneous lymphocyte antigen may be an additional factor facilitating distant extracutaneous migration.

Keywords leprosy.anthiphospholipidantibodyCase PresentationA 29-year-old Brazilian woman was referred for manage-ment of systemic lupus erythematosus (SLE) withantiphospholipid antibodies (aPL). Her symptoms were1 year of intermittent fever and diffuse, tender, erythe-matosus, and nodular rash that began during her firstpregnancy. She was treated with short course of low-dose corticosteroids, with resolution; however, she suf-fered an embryonic loss at 7 weeks. Six months prior toadmission, she had recurrence of the nodular rash withnew onset arthralgia; a skin biopsy showed panniculitis.Tests done at that time showed lupus anticoagulant(LA), anticardiolipin antibody (aCL) IgM >150 U (nor-mal 0–7 U), anti-β

Purpose: To report a well-characterized Waldenstrom's macroglobulinemia (WM) case that provides insight into the mechanisms of two paraneoplastic complications -- cancer-associated retinopathy (CAR) and small fiber polyneuropathy (SFPN).Methods: Retrospective medical chart review.Results: A 58-year old man with WM developed vision loss and bilateral lower extremity pain. CAR was diagnosed by history, a depressed electroretinogram (ERG) and positive anti-retinal antibodies. SFPN diagnosis was based on abnormal autonomic nerve function testing and a distal-leg skin biopsy that demonstrated absent epidermal small-fiber innervation, IgM and complement deposition and microvasculopathy. Plasma exchange (PLEX) led to dramatic pain relief and subjective improvement in eye symptoms along with improvement of some ERG parameters. Repeat skin biopsy after treatment showed less microvascular abnormalities and decreased complement deposition.Conclusions: The concurrence of CAR and SFPN in this patient suggest t...

Susac's syndrome is a rare autoimmune microangiopathy characterized by the clinical triad of encephalopathy, branch retinal artery occlusions, and sensorineural hearing loss. In many cases, the clinical triad is not fully present at the onset of symptoms. MRI studies often show characteristic punched out lesions of the central fibers of the corpus callosum, and leptomeningeal enhancement and deep gray matter lesions may also be seen. Here we present a case of Susac's syndrome in a middle aged man with the unique clinical finding of cauda equina syndrome and spinal MRI showing diffuse lumbosacral nerve root enhancement. Biopsy specimens of the brain, leptomeninges, and skin showed evidence of a pauci-immune endotheliopathy, consistent with pathology described in previous cases of Susac's syndrome. This case is important not only because it expands the clinical features of Susac's syndrome but also because it clarifies the mechanism of a disorder of the endothelium, an important target for many disorders of the nervous system.

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.

Primary cutaneous spindle cell lymphoma is a rare variant of primary cutaneous B-cell lymphoma (PCBCL). Herein, we present 3 cases of primary cutaneous spindle cell B cell lymphoma, 2 males and one female (age range 66–76 years). The patients presented with solitary skin lesions, distributed in the head and neck area and chest. The dominant cell size was in the intermediate to large cell size range. While the main cell type was a spindled one, other cells with a nuclear morphology quite typical for a centroblast were noted and as well careful inspection in the three cases revealed a focal residuum of germinal center-like structures. The spindled cells exhibited a B cell follicle center cell phenotype as revealed by expression of CD20, CD79a, BCL6, and CD10. BCL2 was negative in two cases and positive in one case. The proliferation index exceeded 80%. In one case the neoplastic cells were CD30 positive. Subsequent to a diagnosis in each case of follicle center cell lymphoma, the patients underwent complete excision with no known recurrence. In our review of the literature, a total of 42 other cases were reported showing a similar male predominance with the commonest sites of involvement being the head and neck area and upper back. Other than one patient who died of progressive disease due to treatment refusal and one patient who developed metastatic disease to the liver all patients are alive and well without recurrent or metastatic disease. In summation, our experience along with the reported cases suggest the categorization of primary cutaneous spindle cell B cell lymphoma as a variant of primary cutaneous indolent follicle center lymphoma. It is a neoplasm of middle aged to older adults with a predominance in males which can be treated locally in most cases whereby recurrent and metastatic disease following complete removal is uncommon.

We describe an interesting case of pleomorphic fibroma of the subungual region in a middle aged woman who presented with a recurrence of thickening, lateral ridging, and a midline split of the right third fingernail, 20 years after initial excision. Histology of the specimen demonstrated hyperchromatic stellate cells within the superficial corneum, which were CD34 positive, consistent with a pleomorphic fibroma. Pleomorphic fibroma is a rare mesenchymal neoplasm characterized by atypical spindled cells amidst a collagenous stroma. It is a benign, slow growing tumor that has only been reported in the subungual region twice previously. Although histology may show cellular atypia, the slow-growing benign nature of the tumor, reassuring features histologically i.e low cellularity, and lack of myxomatous change in the stroma, make a conservative approach to therapy reasonable.

Background FISH has recently emerged as a technique to better assess the malignant potential of histologically ambiguous melanocytic lesions. However, the usefulness of FISH has not been conclusively established. The purpose of this study was to further explore the diagnostic value of FISH in distinguishing the borderline melanocytic tumor (BMT) from melanoma. Method 73 cases with BMT were analyzed retrospectively from a dermatopathology database between 2010–2015. FISH studies were conducted in each case using probes targeting 5 loci including CCND1 on 11q13, RREB1 on 6p25, MYB on 6q23, CDKN2A on 9p21, and CEP 6 control probe for chromosome 6. Results The study was composed of 50 females and 23 males with an age range of 1–73 and a mean age of 35 years. Of the 6 cases in the superficial atypical Spitz tumor (AST) category, 2 had indeterminate results due to polyploidy. In the conventional atypical Spitz tumor cases, FISH was positive in 3 of 15 cases. Of the 27 cases in the borderline nevoid tumor (BNM) category, 3 showed positive FISH and 3 were equivocal due to the possibility of polyploidy. 3 of 13 cases of the borderline tumor of deep penetrating nevus variant (B-DPN) were positive for FISH. Neither of the 2 pigmented epithelioid melanocytoma (PEM) cases had positive FISH result. Of the 4 cases in the superficial atypical dermoepidermal nevomelanocytic proliferation group, only 1 met the FISH diagnostic criteria for melanoma. None of the 6 borderline tumors with overlapping features met FISH criteria diagnostic of melanoma. Clinical follow up was available on 55 patients. None of the patients had recurrence nor died of the disease. Lymph node biopsy was performed on five patients without evidence of metastasis. Conclusion Despite the benefits of FISH, it is limited by the fact that melanomas are not genetically identical whereby certain genetic abnormalities are only seen in specific subtypes. Additionally, FISH only targets specific chromosomes resulting in limitations in sensitivity and specificity. Although FISH has proven to be highly sensitive and specific in distinguishing unequivocally benign from malignant lesions, in cases of histopathological ambiguity, these parameters cannot be assessed with great confidence because the histopathological diagnosis (gold standard) is not without uncertainty. The 4-probe set (excluding 9p21) consistently showed chromosomal aberrations throughout all groups, but only 10 of the 73 total cases (13%) met the diagnostic criteria for melanoma. Moreover, it would be wise to establish new cytogenetic reference values that incorporate these borderline lesions in an effort to better assess the possibility of malignant behavior and or define a cytogenetic profile supportive of its categorization as an indeterminate proliferation. Polyploidy is another inherent limitation, which leads to false positives due to the absolute signal counts incorrectly reflecting relative imbalances in the tumor genome.

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.

Idiopathic pulmonary fibrosis is a fatal disease without effective therapy or diagnostic test. To investigate a\ud potential role for c�herpesviruses in this disease, 21 paraffin-embedded lung biopsies from patients diagnosed\ud with idiopathic pulmonary fibrosis and 21 lung biopsies from age-matched controls with pulmonary fibrosis of\ud known etiology were examined for a series of c�herpesviruses’ DNA/RNA and related proteins using in situ\ud hybridization and reverse transcriptase-polymerase chain reaction (RT-PCR)-based methods. We detected four\ud proteins known to be in the genome of several c�herpesviruses (cyclin D, thymidylate synthase, dihydrofolate\ud reductase, and interleukin-17) that were strongly co-expressed in the regenerating epithelial cells of each of the\ud 21 idiopathic pulmonary fibrosis cases and not in the benign epithelia of the controls. Among the c�\ud herpesviruses, only herpesvirus saimiri expresses all four of these ‘pirated’ mammalian proteins. We found\ud herpesvirus saimiri DNA in the regenerating epithelial cells of 21/21 idiopathic pulmonary fibrosis cases using\ud four separate probe sets but not in the 21 controls. RT-PCR showed that the source of the cyclin D RNA in active\ud idiopathic pulmonary fibrosis was herpesvirus saimiri and not human. We cloned and sequenced part of\ud genome corresponding to the DNA polymerase herpesvirus saimiri gene from an idiopathic pulmonary fibrosis\ud sample and it matched 100% with the published viral sequence. These data are consistent with idiopathic\ud pulmonary fibrosis representing herpesvirus saimiri-induced pulmonary fibrosis. Thus, treatment directed\ud against viral proliferation and/or viral-associated proteins may halt disease progression. Further, demonstration\ud of the viral nucleic acids or proteins may help diagnose the disease.

Atypical hemolytic uremic syndrome (aHUS) is one of the prototypic thrombotic microangiopathies which arises from a genetically-based defect in the regulatory control of the alternate complement cascade. Although its cause is distinct, it shares a similar clinical presentation with thrombotic thrombocytopenic purpura with respect to its pattern of organ involvement, with most cases including the renal, central nervous, and gastrointestinal systems. Renal dysfunction in aHUS is generally recognized as a clinical hallmark of the disease. We report a unique case of aHUS in a 71-year-old female highlighted by predominant effect on the gastrointestinal system concurrent with preservation of renal function and histopathologically-proven involvement of skin. J Hematol. 2015;4(3):193-195 doi: http://dx.doi.org/10.14740/jh205w

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.

A 22-year-old man with systemic lupus erythematosus (SLE) presented with 2 weeks of a generalized rash and oral ulcers. The patient was diagnosed with SLE at the age of 3 based onmalar rash, photosensitivity, oral ulcers, and arthritis, which were controlled with chronic low-dose corticosteroids and hydroxychloroquine. At the age of 18, the patient developed aseptic meningitis and acute left anterior uveitis; both were responsive to increased doses of corticosteroids. He did not follow up with a rheumatologist for approximately 4 years, during which time he took no medication until 4 months prior to admission when he experienced a lupus flare with malar rash, oral ulcers, fatigue, and neuropsychiatric symptoms including severe headache, distal paresthesias, slurred speech, and a subacute decline in mental status (difficulty concentrating, slowing thoughts, word finding difficulties, and memory loss). Laboratory testing at that time revealed a moderately high titer positive antinuclear antibody (ANA), in a coarse speckled pattern, and anti-double-stranded deoxyribonucleic acid (anti-dsDNA) antibody, normal levels of C3 and C4 and positive Ro (SS-A), Smith (Sm), U1-ribonucleoprotein, anticardiolipin immunoglobulin A (IgA) (42U), and Beta-2 glycoprotein-I IgA (57U) antibodies. The patient was treated with high-dose corticosteroids, started on hydroxychloroquine 200mg twice daily, aspirin 81mg, and esomeprazole 40mg once daily, with clinical improvement. Patient was subsequently tapered down on prednisone therapy accordingly from 60 to 40mg once daily regimen. Two weeks prior to admission at our institution, the patient developed new oral ulcers and generalized rash. The rash, which was minimally pruritic, initially appeared on his hands and arms, and then extended to his trunk and face, sparing his lower extremities and buttocks. Small painful vesicular lesions with serous discharge developed on his palms and fingers. His oral ulcers, initially discrete and small, became diffuse and painful and made it difficult for him to eat, as per patient's selfreport. He sought care at an emergency department at another institution where he was treated with intravenous valacycloir for possible disseminated herpes-simplex viral (HSV) infection and with vancomycin for a possible bacterial skin superinfection. Less than 24h there, the patient left against medical advice, and presented to our hospital the following day. The patient denied joint pain, neurological symptoms, fevers or chills, chest pain, shortness of breath, cough, diarrhea, constipation, dysuria, or hematuria. The patient had known allergies to penicillin and erythromycin, but no history of recent exposure to these drugs. His medications were prednisone 40mg alternating with 20mg daily, hydroxychloroquine 200mg twice daily, aspirin 81mg daily, and esomeprazole HSSJ (2013) 9:289–292 DOI 10.1007/s11420-013-9356-6

Summary Background Cutaneous squamous cell carcinoma (SCC) with no demonstrable point of epidermal origin is problematic as it raises consideration of metastatic SCC histologically. There are rare case reports and series of SCC arising from the wall of hair follicle structures. Such lesions have been termed follicular SCC (FSCC). Objectives To investigate the clinicopathological features of FSCC. Methods We prospectively collected cases of follicular SCC over a 5-year period. Follicular SCC is defined as a cutaneous SCC deriving from a pre-existing hair follicle structure. Lesions were considered to represent ‘hybrid’ SCCs if an interfollicular epidermal origin was also demonstrated; SCCs with > 50% of the origin from interfollicular epidermis were excluded. Histological features and clinical information were evaluated. Results We identified 61 cases of follicular SCC arising in 60 patients from a database of 5212 cutaneous SCCs encountered over the same time period by the same authors. There were 49 pure follicular SCCs and 12 hybrid lesions. The male to female ratio was 44 : 16; the mean age was 74 years (range 44–93). Follicular SCC represents 1·2% of all primary SCCs. Biopsies of such lesions, if the appendage structure of origin is not represented, are histologically indistinguishable from metastatic SCC. Conclusions Recognition of this under-reported form of SCC is essential if an inappropriate diagnosis of metastatic SCC, with potentially harmful and inappropriate therapy and investigation, is to be avoided.