Blau Syndrome With Delayed Cutaneous Manifestations: A Case Report.

ABSTRACT: Blau syndrome is a rare familial autoinflammatory disorder characterized by the triad of granulomatous dermatitis, polyarthritis, and uveitis. Blau syndrome exhibits an autosomal dominant inheritance pattern and can be caused by a gain-of-function mutation in nucleotide-binding oligomerization domain 2 (NOD2), a member of the NOD-like receptor family of pattern recognition receptors. Mutations in NOD2 cause upregulation of inflammatory cytokines and resultant autoinflammation. Because of the rarity of this condition and early onset of symptoms, Blau syndrome may be misdiagnosed as juvenile idiopathic arthritis. We present a case of a 37-year-old male patient with a long-documented history of juvenile idiopathic arthritis and uveitis, who developed an asymptomatic eruption of pink papules on the trunk and upper extremities. A biopsy demonstrated noncaseating, well-formed dermal granulomas with relatively sparse lymphocytic inflammation and Langerhans-type giant cells. Genetic testing confirmed a mutation in NOD2. Based on the patient's clinical history, histologic findings, genetic testing, the diagnosis of Blau syndrome was made.

A Comparison of Preferentially Expressed Antigen in Melanoma Immunohistochemistry and Diagnostic Gene Expression-Profiling Assay in Challenging Melanocytic Proliferations.

ABSTRACT: Most melanocytic tumors are classified as benign or malignant based on clinical morphology, histology, and immunohistochemical (IHC) analysis. A subset of more challenging cases with ambiguous features may require further evaluation with established ancillary diagnostic molecular studies, including fluorescence in situ hybridization and/or single nucleotide polymorphism array, to increase diagnostic certainty. More recently, a diagnostic gene expression-profiling (GEP) assay and an IHC stain for the detection of PRAME (PReferentially expressed Antigen in MElanoma) have been developed. The use of PRAME IHC has been validated in cases of unequivocal and ambiguous melanocytic proliferations via comparing results with fluorescence in situ hybridization and/or single nucleotide polymorphism array. A study comparing performance metrics of PRAME IHC and diagnostic GEP has not been previously published. Herein, we evaluated the use of PRAME IHC in 55 melanocytic tumors with challenging histomorphology by comparing the results with diagnostic GEP and final histomorphologic diagnosis. Intertest agreement occurred in 88% of cases. PRAME IHC supported the final diagnosis in 89% of cases with a sensitivity of 79%, specificity of 95%, and positive predictive value of 88.2%. GEP agreed with the final diagnosis in 88% of cases with a sensitivity of 65%, 97% specificity, and positively predicted melanoma in 91.7% of cases. Because the results of this study align with past publications evaluating the performance metrics of PRAME IHC, showing it to be as sensitive as and more cost effective than all other ancillary molecular tests, we propose the use of PRAME IHC as the optimal first-line diagnostic tool for ambiguous melanocytic proliferations.

Mpox Case Presenting With Genital Lesions and Proctitis.

ABSTRACT: Monkeypox (Mpox) is a zoonotic Orthopoxvirus of the Poxviridae family, endemic to Africa. In August 2022, the US government declared it an emergency because of the worldwide spread. Traditionally, Mpox infection spreads through contact with infected animals. However, the 2022 outbreak Centers for Disease Control and Prevention (CDC) data note that 94% of cases had recent male-to-male sexual or close intimate contact, suggesting a novel sexual transmission. In this article, we report a 39-year-old HIV-positive man presenting with a diffuse cutaneous rash, perianal pain, and bloody stool of 2-week duration. A medical history includes intravenous drug use and multiple sexual partners. Physical examination revealed umbilicated, tan-colored, crusted cutaneous papules scattered across the face, trunk, and genital regions. Perianal lesion biopsy showed an acanthotic epidermis with spongiosis, ballooning degeneration of keratinocytes, and the formation of multinucleated syncytial keratinocytes. A dermal superficial/lichenoid mixed inflammatory cell infiltrate with multinucleated giant cells was noted. Perianal lesion polymerase chain reaction (PCR) was positive for Mpox. Colonoscopy revealed a 3-cm circumferential rectal ulcer with gray exudate and necrosis. A rectal ulcer biopsy showed an ulcerated mucosa with acute proctitis and necrosis. There were scattered macrophages with intranuclear inclusion and glassy vacuolization, and Mpox infection was confirmed by immunostaining with a Mpox-specific anti-Vaccinia virus antibody.

Acute generalized exanthematous pustulosis associated with clindamycin in a patient with Hailey-Hailey disease.

A 61-year-old African-American female with moderately controlled Hailey-Hailey disease (HHD) presents to the emergency department with a rash and fever. One day prior to her presentation, she was started on oral clindamycin for a tooth extraction procedure. Her physical examination shows diffuse erythema on the trunk and extremities with multiple nonfollicular pustules. A punch biopsy of her upper extremity revealed intraepidermal acantholysis, neutrophilic spongiosis, and subcorneal pustules. The perivascular and interstitial superficial dermal infiltrate is mixed and composed of predominantly neutrophils, with lymphocytes and rare eosinophils. These findings suggest a superimposed acute generalized exanthematous pustulosis (AGEP) in the background of HHD. AGEP is a potentially severe cutaneous condition characterized by the abrupt onset of numerous nonfollicular pustules in a background of pruritic edematous erythroderma. To date, only two case reports have described AGEP in patients with HHD. Early diagnosis of AGEP is essential to initiate prompt and aggressive systemic therapy, prompt medication cessation, close monitoring for end-organ damage, and improve overall morbidity and mortality.

Gene expression profiling and multiplex immunofluorescence analysis of bullous pemphigoid immune-related adverse event reveal upregulation of toll-like receptor 4/complement-induced innate immune response and increased density of TH 1 T-cells.

BACKGROUND: Immune checkpoint inhibitor (ICI)-based cancer therapies cause a variety of cutaneous immune-related adverse events (irAEs) including immunobullous skin eruptions like bullous pemphigoid (BP). However, little is known about the underlying immunopathogenic drivers of these reactions, and understanding the unique gene expression profile and immune composition of BP-irAE remains a critical knowledge gap in the field of oncodermatology/oncodermatopathology. METHODS: BP-irAE (n = 8) and de novo BP control (n = 8) biopsy samples were subjected to gene expression profiling using the NanoString® Technologies nCounter PanCancer Immune Profiling Panel. Multiplex immunofluorescence (mIF) studies using markers for T-cells (CD3 and CD8), T helper 1 (TH 1) cells (Tbet), TH 2 cells (Gata3), TH 17 cells (RORγT), and regulatory T-cells (Tregs; FoxP3) were further evaluated using InForm® image analysis. RESULTS: Compared with de novo BP controls, BP-irAE samples exhibited upregulation of 30 mRNA transcripts (p < 0.025), including toll-like receptor 4 (TLR4) and genes associated with complement activation, and downregulation of 89 mRNA transcripts (p < 0.025), including genes associated with TH 2, TH 17, and B-cell immune response. BP-irAE demonstrated a greater density of Tbet+ (TH 1) cells in the dermis (p = 0.004) and fewer Tregs in the blister floor (p = 0.028) when compared with that of de novo control BP samples. CONCLUSIONS: BP-irAE exhibited activation of the TLR4/complement-driven classical innate immune response pathway, with dermal TH 1 immune cell polarization and decreased Tregs in the blister floor. TLR/complement signaling may underlie the immunopathogenesis of BP-irAE.

Solitary Vulvar Syringoma With Deep Extension; Potential for Misdiagnosis as the Microcystic Adnexal Carcinoma (MAC).

ABSTRACT: A 43-year-old woman presented with a palpable, pruritic, minimally painful right vulvar lesion. Physical examination revealed approximately 2.0-cm tender nodule at 70' clock in the right labia majora. Histological sections of the excision specimen showed an unremarkable epidermis with large, well-circumscribed dermal proliferation with extension to the reticular dermis. Within this proliferation are small solid and ductal structures relatively evenly distributed in the sclerotic stroma. The epithelial elements consisted of monomorphous cuboidal cells and assumed round, oval, curvilinear, or have other peculiar geometric shapes, including "comma-like" or "tadpole"-like configurations. The tumor cells were positive for CEA, EMA, and estrogen receptor and negative for progesterone receptor. The clinical presentation and the deep extension of the tumor were similar to the microcystic adnexal carcinoma. Although a syringoma generally presents with multiple lesions and usually involves the superficial dermis, a syringoma with deep extension was favored based on the lack of follicular differentiation, atypia, mitoses, and perineural invasion. Microcystic adnexal carcinoma and syringoma have a morphologic overlap and are misdiagnosed in 30% of the cases. Thus, it is exceptionally important for pathologists to be aware of and be able to distinguish these entities. To the best of our knowledge, this is the first case of a solitary, painful vulvar syringoma with deep extension.

Primary Cutaneous Ewing Sarcoma of the Scalp With Metastasis to the Lung: An Unusual Manifestation During Pregnancy.

ABSTRACT: A 32-year-old G2P1L1 (5 months pregnant) woman presented with a 3-month history of a slow-growing cystic lesion on her scalp vertex. Similar lesions in the exact location were excised twice in the past with a diagnosis of trichilemmal carcinoma (TC). A biopsy of the scalp lesion showed morphology and immunoprofile consistent with previously diagnosed TC. Staging PET/CT demonstrated a 4.7 cm right upper lobe lung, and a subsequent lung biopsy showed a small, round blue-cell tumor with necrosis, morphologically identical to the prior biopsies from the scalp. Considering the unusual clinical course of TC, a lung biopsy was sent for next-generation sequencing that showed EWSR1-FLI1 (type1) fusion. Additionally, CD99 immunostaining revealed uniform cytoplasmic and membranous staining in the tumor cells. The previous scalp excision specimen was also sent for mutation analysis, which showed EWSR1-FLI1 fusion. In conjunction with clinical history and histological and molecular findings, a definitive diagnosis of primary cutaneous Ewing sarcoma (PCES) with local recurrence and metastasis to the lung was made. We present a case of PCES, which was previously misdiagnosed and treated as TC. This case emphasizes the importance of CD99 in the initial screening of cutaneous small round blue-cell tumors to avoid misdiagnosis from other morphological overlaps. Also, despite its rarity, PCES should be included in the differential diagnosis of small, round, blue cell tumors at cutaneous sites. Our case also exemplifies common biases in medical decision-making, including premature closure and anchoring bias which can result in misdiagnosis or diagnostic delay and associated delay in appropriate management.

Disseminated Protothecosis Due to Prototheca zopfii and Literature Review.

ABSTRACT: Prototheca species are achlorophyllic algae that are a rare cause of infection in humans. It most commonly causes localized cutaneous disease and rarely disseminated infection. Immunocompromised patients have the highest risk of disseminated protothecosis, with a higher mortality rate than localized cutaneous infections. At the species level, infections caused by Prototheca zopfii are reported less frequently than those caused by Prototheca wickerhamii. The diagnosis can be made using histopathology, culture, and molecular testing. There is no definitive evidence for an effective treatment, which currently consists of antifungals (primarily amphotericin B). With only a handful of cases of disseminated protothecosis reported worldwide that are caused by P. zopfii , we herein present an additional case of a postbone marrow transplant patient in the Midwest of the United States.

A rare case of papular-purpuric "gloves and socks" syndrome associated with influenza.

Papular-purpuric "gloves and socks" syndrome (PPGSS) is a unique, self-limited dermatosis characterized by edema, erythema, and pruritic petechiae and papules in a distinct "gloves and socks" distribution. This is often accompanied by systemic symptoms, including fever, lymphadenopathy, asthenia, myalgia, and arthralgias. PPGSS has also been described as a manifestation of an underlying immunological mechanism that can be triggered by viral or drug-related antigens. A 32-year-old male developed a painful eruption on the bilateral hands and feet after being diagnosed with influenza B. On examination, scattered papular purpura with occasional overlying scale was noted on the bilateral hands, fingers, feet, toes, volar wrists, and ankles. Histopathologic sections showed a mixed pattern of inflammation with interface and spongiotic changes. A parakeratotic scale with overlying basket-weave orthokeratosis was also seen. Within the epidermis, there was intraepidermal vesicles and Langerhans cell microabscess formation with scattered apoptotic keratinocytes. The underlying dermis showed a superficial perivascular lymphocytic infiltrate with mild edematous changes, and extravasation of red blood cells. Clinicopathologic correlation strongly supported a diagnosis of popular-purpuric gloves and socks syndrome. The influenza virus has never been reported in association with PPGSS; thus, this case outlines an important new variant that clinicians should be familiar with.

Mechanic Hands/Hiker Feet in a Patient With Amyopathic Dermatomyositis and Interstitial Lung Disease.

ABSTRACT: A 30-year-old African American woman with a history of interstitial lung disease presented with bilaterally symmetrical, nonpruritic, scaling and fissuring, hyperpigmented, lichenified plaques on her hands and feet. She reported occasional erythema of her face, intermittent erythema, and irritation of her eyes but denied any muscle weakness. A biopsy of the plantar first toe showed hyperkeratosis, striking alternating ortho- and parakeratosis with underlying apoptotic bodies. There was psoriasiform acanthosis without suprapapillary thinning, numerous apoptotic keratinocytes in all layers of the epidermis extending into the corneum that were out of proportion with the minimal interface inflammation. Colloidal iron and Alcian blue stains showed increased dermal mucin deposition. Given the clinical, histopathological, and supportive serological findings (positive anti-KU and anti-SSA), a diagnosis of clinically amyopathic dermatomyositis with mechanic hand/hiker feet (MH/HF) was rendered. The pseudocheckerboard pattern of MH/HF has been previously reported in only 4 patients. The most frequent associations with MH/HF are dermatomyositis and antisynthetase syndrome; however, our patient was negative for antiaminoacyl transfer RNA synthetase antibodies, a required criterion to diagnose antisynthetase syndrome. It is imperative to recognize MH/HF clinically and histopathologically because it may be an early indication of developing dermatomyositis or other connective tissue diseases, which would guide further workup and screening for systemic involvement of the disease, including interstitial lung disease.

A Case of Primary Myelofibrosis With Transformation to Leukemia Cutis.

ABSTRACT: We report an extraordinary case of primary myelofibrosis with transformation to leukemia cutis. A 64-year-old Caucasian man with a history of JAK2-positive primary myelofibrosis presented with erythematous papulonodules on his right lower extremity. A punch biopsy revealed a normal epidermis with an underlying diffuse dermal infiltrate composed of medium-to-large-sized myeloid cells and leukocytes. Neoplastic cells were immunoreactive for LCA, CD34, CD61, CD117, and CD68 and negative for lysozyme, CD20, CD3, myeloperoxidase, and TdT. These findings were consistent with a diagnosis of leukemia cutis. A concurrent bone marrow biopsy demonstrated a markedly fibrotic, hypercellular marrow without a significant increase in blasts. With no morphologic evidence of bone marrow involvement by acute myeloid leukemia, our case suggests that the patient's primary myelofibrosis transformed to leukemia cutis. Our patient died 2 months after the onset of his skin nodules. Our case demonstrates that leukemia cutis should be included in the differential diagnosis for cutaneous nodular lesions in patients with a history of an advanced-stage hematological malignancy.

Chronic myeloid leukemia-leukemia cutis mimicking a neutrophilic panniculitis-like leukemia cutis: Report of a rare case.

While drug-induced panniculitis is not uncommon in chronic myeloid leukemia (CML) patients on tyrosine kinase inhibitor therapy, it is rare for CML to initially present as a leukemic panniculitis. We present the case of a 45-year-old male with no relevant prior medical history presenting with 6 months of migratory nodules, 2 months of drenching night sweats, and a 20 pound weight loss. Physical examination showed firm subcutaneous nodules with overlying ecchymoses present on the right lateral thigh and left lower back. Biopsy of a nodule from the right thigh showed a subcutaneous lobular panniculitis involved by a dense infiltrate of neutrophils and granulocyte precursors. Fluorescent in-situ hybridization (FISH) was positive for t(9;22)(q34;q11.2)BCR-ABL1 fusion. A concurrent hemogram revealed a white blood cell count elevation of 600,000 K/µL. Bone marrow biopsy examination showed marked myeloid expansion with an increase in granulocyte precursors and Philadelphia chromosome positivity by FISH, consistent with bone marrow involvement by CML. Herein, we describe this unusual and rare case of CML initially presenting as a neutrophilic panniculitis-like leukemia cutis. Arriving at this challenging diagnosis may be easily missed without clinical and laboratory correlation, which would certainly lead to the patient's not receiving life-saving treatment.

A comparison of imaging software and conventional cell counting in determining melanocyte density in photodamaged control sample and melanoma in situ biopsies.

BACKGROUND: Objective methods for distinguishing melanoma in situ (MIS) from photodamaged skin (PS) are needed to guide treatment in patients with melanocytic proliferations. Melanocyte density (MD) could serve as an objective histopathological criterion in difficult cases. Calculating MD via manual cell counts (MCC) with immunohistochemical (IHC)-stained slides has been previously published. However, the clinical application of this method is questionable, as quantification of MD via MCC on difficult cases is time consuming, especially in high volume practices. METHODS: ImageJ is an image processing software that uses scanned slide images to determine cell count. In this study, we compared MCC to ImageJ calculated MD in microphthalmia transcription factor-IHC stained MIS biopsies and control PS acquired from the same patients. RESULTS: We found a statistically significant difference in MD between PS and MIS as measured by both MCC and ImageJ software (P < 0.01). Additionally, no statistically significant difference was found when comparing MD measurements recorded by ImageJ vs those determined by the MCC method. CONCLUSION: MD as determined by ImageJ strongly correlates with the MD calculated by MCC. We propose the use of ImageJ as a time-efficient, objective, and reproducible tool to assess MD.

A Rare Case of Lichen Planus-Like Atopic Dermatitis Involving the Hands.

Lichen planus-like atopic dermatitis clinically mimics lichen planus and can pose a diagnostic challenge. We report a case of a 55-year-old African American woman who developed intensely pruritic papules and plaques on bilateral hands. Histological examination demonstrated acute spongiotic dermatitis with lymphocyte exocytosis into the epidermis. Taken together, a diagnosis of lichen planus-like atopic dermatitis was made. This case serves to highlight that lichen planus-like atopic dermatitis can develop on hands and that it presents as spongiotic dermatitis with lymphocyte exocytosis into the epidermis. Correlating the clinical presentation with histopathological findings will assist in establishing the diagnosis and guiding appropriate management.

Clonal highlights: Clonal seborrheic keratoses often demonstrates p16 expression.

BACKGROUND: At times, distinguishing Bowen disease (BD) and benign seborrheic keratosis (SK) is histologically challenging, especially when SK shows clonal features (clonal seborrheic keratosis [CSK]). While p16 is often reported as positive in BD and negative in SK, p16 expression in CSK is rarely studied. Here we investigate p16 immunohistochemistry in CSK, SK, and BD. METHODS: p16 immunohistochemistry with pattern of expression was noted for 14 CSK, 12 SK, and 18 BD. The degree of inflammation among lesions with respect to p16 expression was also noted. RESULTS: When examining p16 staining in clonal nests of CSK, 57% showed diffuse or patchy/diffuse positivity, 21% showed patchy positivity, and 21% showed clusters of single positive cells. 67% of BD showed diffuse positivity, 11% showed patchy/diffuse positivity, 17% showed patchy positivity, and 6% were negative. 25% of SK showed focal areas of patchy to full thickness positivity, 25% showed moderate number of positive single cells with or without patchy staining, and 50% showed negative/scattered single cell positivity. CONCLUSION: Our findings support that p16 positivity limited to clonal nests in CSK is normal. p16 positivity in clonal nests of CSK in isolation without concurrent atypical histologic features should not be used to support a diagnosis of BD.

Regulatory T-cells in alopecia areata.

BACKGROUND: Alopecia areata (AA) is believed to have an autoimmune mechanism in which the hair follicles are targeted by CD4+ and CD8+ lymphocytes. Studies investigating the autoimmune mechanism of other cutaneous diseases, including vitiligo, showed that Treg is a component of cutaneous immune privilege. Our study uses immunohistochemical staining in formalin-fixed, paraffin-embedded tissue to examine the percentage of CD4+ FoxP3+ , CD25+ FoxP3+ , and CD8+ FoxP3+ Treg in AA in human specimens. METHODS: Immunohistochemical double staining for CD4+ FoxP3+ , CD25+ FoxP3+ , and CD8+ FoxP3+ was performed on 12 AA cases and 12 other autoimmune and non-autoimmune cutaneous diseases. The frequency of CD4+ FoxP3+ , CD25+ FoxP3+ , and CD8+ FoxP3+ Treg was counted and expressed as a percentage of total CD4+ , CD25+ , and CD8+ lymphocytes, respectively, in order to account for intersample inflammatory response variability. RESULTS: There was a significant reduction in the mean frequency of CD4+ FoxP3+ and CD25+ FoxP3+ in AA when compared to other autoimmune and non-autoimmune cutaneous diseases. CONCLUSION: Treg is significantly lower in AA when compared to other cutaneous diseases. Additionally, this immunohistochemical-staining protocol may be useful to evaluate Treg in formalin-fixed, paraffin-embedded specimens for other cutaneous diseases. Studies examining Treg in AA and other cutaneous diseases may have implications for future interventions.

Is melanocyte density our last hope? Comparison of histologic features of photodamaged skin and melanoma in situ after staged surgical excision with concurrent scouting biopsies.

Differentiating melanocytic hyperplasia (MH) on photodamaged skin from junctional lentiginous melanocytic proliferations (JLMP), early evolving melanoma in situ (MIS), or the periphery of a lesion of MIS on staged excision can be challenging. Although previous cross-sectional studies have elucidated important criteria for distinguishing MH on photodamaged skin from more concerning lesions, this study highlights a technique to treat JLMP and MIS with staged mapped excision and baseline scouting biopsies of adjacent nonlesional photodamaged skin to assist in determination of surgical margin clearance. Additionally, we compare the lesional and photodamaged control biopsies from the same patient to evaluate relevant histologic criteria that may be used to distinguish MH in photodamaged skin from JLMP/MIS, while minimizing confounding factors. There was a statistically significant difference (P ≤ 0.05) found for melanocyte density, irregular melanocyte distribution, melanocyte clustering, follicular infundibulum involvement, and nesting. However, criteria such as nesting, epithelioid cells and melanocyte clustering were seen in both photodamaged skin and MIS. These findings underscore the fact that histologic features of photodamaged skin can overlap with the histopathological features of MIS. Of all of the criteria evaluated, melanocytic density was the most objective histologic criterion and did not show overlap between the sun-damaged and JLMP/MIS groups.

Cutaneous Cytomegalovirus Infection in an Immunocompetent Patient: Innocent Bystander or Culprit?

We present a rare case of cutaneous cytomegalovirus (CMV) infection in a nonimmunocompromised patient. A 74-year-old woman with a history of diabetes presented with an ulcer on the right lateral tibia that occurred at the site of a nerve core biopsy. Subsequent biopsy of the ulcer edge showed granulation tissue with neutrophilic inflammation. The patient underwent extensive antibiotic treatment for possible infection with weekly wound care. However, the ulceration persisted and enlarged. A repeat biopsy 1 year later showed superficial and deep mixed inflammation with an associated vasculitis. On close examination, endothelial and eccrine ducts cells showed characteristic CMV viral cytopathic changes with positivity on CMV immunohistochemical stain. Although the patient was started on valganciclovir, the ulceration did not resolve with treatment and slightly enlarged. Treatment modalities included dapsone, prednisone, weekly wound care, wound vacuum, and eventually a skin graft of the ulcer site. This case highlights the presence of CMV infection in a cutaneous ulceration in a relatively immunocompetent patient, and the lack of response to treatment raises the question whether CMV was causative, partially contributory, or simply an innocent bystander.

Pernio as the presenting sign of blast crisis in acute lymphoblastic leukemia.

A previously healthy 5-year-old girl presented with acute onset of blue toes and red spots on the nose and fingers. The striking nature of these lesions, along with the finding of submandibular lymphadenopathy, prompted further evaluation. Laboratory findings were remarkable for anemia, high transaminase levels, and high blast count. Histopathologic findings were consistent with early pernio. Further examination revealed acute B-cell lymphoblastic leukemia. Treatment of the leukemia led to resolution of the pernio.

Mucinous hidradenoma in a child-A case report and review of the literature.

Hidradenomas are benign tumors of the sweat glands that are rarely reported in childhood. The presence of mucinous change in hidradenomas, which consists of variable numbers of mucin-rich goblet cells, is occasionally observed in some adult clinical practices. However, it has not been previously reported in the pediatric population. Herein, we present a unique case of a mucinous hidradenoma presenting on the thigh of a 3-year-old boy. The clinical presentation and histological features of the case, along with a literature review of published case reports of pediatric hidradenomas are described. We present this case in order to highlight this variant of hidradenoma and to reinforce its inclusion in the differential diagnosis of neoplasms/conditions of childhood with mucinous differentiation.