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.

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.

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.

Unusual Instance of Mucosa-Associated Lymphoid Tissue (MALT) Lymphoma Confined to a Colonic Polyp.

Extranodal marginal zone lymphoma (EMZL) of mucosa-associated lymphoid tissue (MALT) commonly affects the gastrointestinal (GI) tract but rarely occurs within the colon. Colonic EMZL is a rare diagnosis accounting for 2.5% of EMZL and less than 0.5% of colon cancers. We present a unique case of asymptomatic colonic EMZL diagnosed on a routine surveillance colonoscopy. The lymphoma was confined to a single colonic polyp presenting endoscopically as a sessile polypoid lesion at the recto-sigmoid junction. The patient was successfully treated with polypectomy with no recurrence of the disease.

An Atypical Presentation of an Uncommon Malignancy: Plasmablastic Lymphoma Presenting As Recurrent Scrotal Abscesses.

Plasmablastic lymphoma (PBL) is a rare and extremely diagnostically challenging entity. We report a unique case of PBL in an adult male with a history of recurrent scrotal abscesses who presented with progressively worsening scrotal pain, swelling, and drainage. Pelvic CT demonstrated a large scrotal abscess with external draining tracts with foci of air. Surgical debridement revealed necrotic tissue throughout the abscess cavity, abscess wall, and scrotal skin. Immunohistochemical analysis of the scrotal skin specimen uncovered diffuse proliferation of plasmacytoid cells with immunoblastic features that stained positive for CD138, CD38, IRF4/MUM1, CD45, lambda restriction, and Epstein-Barr encoded RNA in situ hybridization (EBER-ISH) with high Ki-67 proliferation index greater than 90%. Taken together, these findings confirmed a diagnosis of PBL. Treatment with six cycles of infusional etoposide, prednisolone, vincristine, cyclophosphamide, and hydroxydaunorubicin (EPOCH-like regimen) was administered with subsequent positron emission tomography (PET)/CT confirmation of complete response. There was no clinical evidence of lymphoma recurrence at the time of follow-up six months later. Our case exemplifies the growing diversity of ways in which PBL may manifest and underscores the importance of a clinician's familiarity with this entity and its well-defined risk factor of immunosuppression.

HPV Associated Squamous Cell Carcinoma in the Rectal Tonsil.

Mucosa-associated lymphoid tissue has been reported throughout the gastrointestinal tract including rectum. Rarely, a nodular proliferation of predominantly submucosal lymphoid tissue in the rectum has been documented as rectal tonsil. Here we report a patient with HPV-associated squamous cell carcinoma of the rectal tonsil, presenting as a polyp. Previously, rare reports of HPV-associated lymphoepithelial carcinoma have been reported in the literature. We are presenting an extremely rare occurrence and emphasizing the importance of appropriate nomenclature based on the pathogenesis of the neoplasm.

Acute Promyelocytic Leukemia Treatment Masking Hepatic Tuberculosis: A Management Dilemma.

Acute promyelocytic leukemia is a form of acute myeloid leukemia (AML) that is characterized by presence of a promyelocytic leukemia-retinoic acid receptor alpha fusion. In most patients, this fusion is detected on conventional karyotype as the t(15;17)(q24.1;q21.2) translocation, but some patients have cryptic translocations with a normal karyotype. Historically, AML is associated with a poor prognosis. Treatment with all-trans retinoic acid and arsenic trioxide assures long-term survival in the majority of patients. This treatment is generally well-tolerated but may cause hepatotoxicity. This is usually identified by transaminitis but resolves after temporary cessation of treatment. Our patient's hepatotoxicity did not resolve following all-trans retinoic acid and arsenic trioxide cessation which posed a diagnostic dilemma. This prompted exploration of other possible causes of hepatotoxicity. An eventual liver biopsy identified acid-fast bacilli, confirming a diagnosis of hepatic tuberculosis. A broad differential diagnosis is imperative when investigating abnormalities in liver function, especially in chemotherapy patients when treatment cessation may cause cancer progression.

Unusual Instance of Primary Diffuse Large B-cell Lymphoma of the Colon.

Diffuse large B-cell lymphoma (DLBCL) commonly affects the gastrointestinal (GI) tract, although primary DLBCL rarely occurs in the colon. Primary colorectal lymphoma is a surprisingly rare diagnosis, accounting for a minute percentage of GI lymphomas and colorectal malignancies. We present an interesting case of an immunocompromised young adult female who was diagnosed with DLBCL confined to a cecum polyp after she underwent a colonoscopy for a GI bleed. The lymphoma presented endoscopically as a semi-sessile polyp in the cecum that was successfully removed. The patient was treated with appropriate therapy of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP).

Flow Cytometric Findings in Primary Effusion Lymphoma: A Report of Two Cases.

Primary effusion lymphoma (PEL) is a rare B-cell lymphoma that usually occurs in the setting of HIV infection, and it is associated with Human Herpesvirus-8 (HHV-8). Diagnosis of PEL is usually established in cell centrifuge, cell block, or tissue examination, and there are few reports describing flow cytometry findings in PEL. We report two male patients (a 34-year-old and a 56-year-old) with a history of HIV infection. The first patient presented with ascites and abdominal pain, and the second patient presented with chest pain and parapneumonic pleural effusion. Cavitary fluid examination showed large pleomorphic neoplastic lymphoid cells with plasmablastic morphology. Flow cytometry analysis of the neoplastic lymphocytes showed increased forward scatter and side scatter with intermediate to a high level of CD38 expression. In one patient, lymphoma cells showed bright CD45 expression with dim expression of CD19 and kappa light chain. There was no significant expression of CD20 or any T/NK cell markers in either case. Immunohistochemistry for CD30 was positive in one patient. Immunohistochemistry for HHV-8 and in situ hybridization for Epstein-Barr virus-encoded small RNAs (EBER) was positive on cell blocks in both cases, consistent with the diagnosis of primary effusion lymphoma. PEL should be considered in the differential diagnosis of CD20-negative hematopoietic neoplasms, and flow cytometry may provide helpful clues for the diagnosis of PEL as part of the workup for pleural effusion with cytologically malignant cells.

A Case of Undifferentiated Pleomorphic Sarcoma.

Suspicion for soft tissue malignancy of the hand is usually low because most tumors of the hand are small and benign. We present a case of an elderly female who presented with a rapidly enlarging, ulcerating hand mass over a few months. She was diagnosed with undifferentiated pleomorphic sarcoma (UPS), a high-grade, aggressive soft-tissue sarcoma. Computed tomography (CT) of the chest was conducted for staging purposes. It showed multiple subcentimeter pulmonary nodules, findings that were initially worrisome for metastatic disease but later proved to be newly and incidentally diagnosed granulomatous disease of the lungs. This case highlights the importance of early recognition of potential malignancy in soft-tissue tumors of the hand to facilitate proper referral and initiation of appropriate oncologic therapies. Due to early diagnosis and intervention, our patient had locally advanced disease without metastasis, a type of cancer known to have a high degree of metastatic potential.

Rituximab Used for the Treatment of Nonuremic Calciphylaxis: A Complication of Prolonged Steroid Use in Lupus Nephritis.

Nonuremic calciphylaxis (NUC) is a rare and debilitating form of panniculitis. NUC is associated with a high mortality rate within the first year of diagnosis. Connective tissue diseases account for a small fraction of the reported cases. However, there have also been reported cases of patients developing NUC while on treatment with chronic corticosteroid immunosuppressive therapy. The pathophysiology of NUC is still not fully established. Several risk factors including underlying diseases, obesity, female gender, and medications have been associated with the development of NUC. The diagnosis remains challenging due to the condition's similarities with other forms of panniculitis. The gold standard for diagnosis is a tissue biopsy showing calcifications within the medial layer of arterioles and the presence of microthrombi with surrounding necrosis. The treatment for NUC has not advanced much in recent years and focuses on the management of the underlying condition, wound care, and treating any superimposed infection. Treating superimposed infections remains important as most of the associated mortality from NUC occurs due to sepsis. We describe a case of a young woman with lupus nephritis who developed NUC while on prolonged corticosteroid therapy. She did not respond to several immunosuppressive agents and was ultimately treated with rituximab, a monoclonal antibody against CD20 antigen, as salvage therapy.

Multiple myeloma with extensive AL amyloidosis presenting as chronic diarrhoea.

We present a 52-year-old man admitted to the hospital with diarrhoea and lower extremity weakness ongoing for the past 3 months. The patient was found to have malabsorptive diarrhoea, hypoproliferative anaemia and renal insufficiency with proteinuria. Extensive workup was performed including a bone marrow biopsy with 20% plasma cells, renal and duodenal biopsies with Congo-red staining revealed amyloid deposition. The patient was diagnosed with multiple myeloma and amyloidosis with gastrointestinal, kidney and nerve involvement explaining his presentation with diarrhoea, renal insufficiency and weakness. Throughout his admission, there were incidental findings of asymptomatic hypoglycaemia (serum blood glucose <40 mg/dL), which was later found to be caused by anti-insulin monoclonal antibodies produced by the neoplastic plasma cells. This is an extremely rare manifestation of multiple myeloma with only a few cases reported in the literature.

MR imaging findings of calcinosis cutis in primary Sjogren syndrome, a rare manifestation.

Soft tissue calcifications associated with various connective tissue diseases such as dermatomyositis and scleroderma have been well documented Plaque-like sheets of subcutaneous calcifications presenting as an indurated soft tissue mass in a patient with primary Sjogren syndrome have been rarely documented in the literature. We present the magnetic resonance and conventional radiographic findings of calcinosis cutis and calcinosis circumscripta of a 47-year-old woman with biopsy proven Sjogren syndrome. We also delineate various types of soft tissue calcification, histopathology of calcinosis cutis, and current treatment options. Recognizing the magnetic resonance characteristics of this phenomenon may prove useful to radiologists, especially in the absence of clinical history and conventional radiographs.

Follicular Dendritic Cell Sarcoma or Not? A Series of 5 Diagnostically Challenging Cases.

Imperfect or unusual presentation, morphology, or immunophenotype can make the diagnosis of follicular dendritic cell sarcoma (FDCS) very challenging. To illustrate this, we present 5 unique cases from the archives of our tertiary care academic medical center that presented a diagnostic challenge wherein FDCS was the top differential diagnostic possibility. The workup of these cases, including multiple expert consultations, highlights the importance of avoiding specific pitfalls in the diagnosis of FDCS.

Revisiting Howell-Jolly Body-Like Cytoplasmic Inclusions in Neutrophils: A Report of Two Cases and Confirmation of Nuclear Origin.

Howell-Jolly body-like inclusions in neutrophils have been reported in a handful of reports; however, their nuclear origin has never been confirmed to date. We report the presence of these cytoplasmic inclusions in two cases and confirm their DNA-based origin by fluorescent nuclear staining. Peripheral blood smears were manually reviewed by light microscopy and after 4',6-diamidino-2-phenylindole (DAPI) fluorescent staining via confocal microscopy. Methanol fixed peripheral blood smears were incubated with DAPI (Sigma Aldrich, St. Loius, MO, USA) and coverslipped with mounting media. DAPI-stained cells were imaged with a Leica SPE confocal microscope using a 405 nm excitation laser and a 63×/1.3 NA oil immersion objective. Optical sections spanning the entire cell thickness were acquired and maximum intensity projections were produced in ImageJ. Both cases described herein had Howell-Jolly body-like inclusions similar to those reported in the literature. Testing for relevant infectious etiologies was negative. Positive staining on fluorescence microscopy confirmed DNA-based origin of this cytoplasmic inclusion material. These DNA-based inclusions occur in the immunosuppressed patient and mimic infectious inclusions. While morphologically worrisome, recognition of these inclusions may prevent unnecessary treatment and testing in clinically appropriate patients.