ALK-negative anaplastic large cell lymphoma is a genetically heterogeneous disease with widely disparate clinical outcomes.

Anaplastic lymphoma kinase (ALK)-negative anaplastic large cell lymphoma (ALCL) is a CD30-positive T-cell non-Hodgkin lymphoma that morphologically resembles ALK-positive ALCL but lacks chromosomal rearrangements of the ALK gene. The genetic and clinical heterogeneity of ALK-negative ALCL has not been delineated. We performed immunohistochemistry and fluorescence in situ hybridization on 73 ALK-negative ALCLs and 32 ALK-positive ALCLs and evaluated the associations among pathology, genetics, and clinical outcome. Chromosomal rearrangements of DUSP22 and TP63 were identified in 30% and 8% of ALK-negative ALCLs, respectively. These rearrangements were mutually exclusive and were absent in ALK-positive ALCLs. Five-year overall survival rates were 85% for ALK-positive ALCLs, 90% for DUSP22-rearranged ALCLs, 17% for TP63-rearranged ALCLs, and 42% for cases lacking all 3 genetic markers (P < .0001). Hazard ratios for death in these 4 groups after adjusting for International Prognostic Index and age were 1.0 (reference group), 0.58, 8.63, and 4.16, respectively (P = 7.10 × 10(-5)). These results were similar when restricted to patients receiving anthracycline-based chemotherapy, as well as to patients not receiving stem cell transplantation. Thus, ALK-negative ALCL is a genetically heterogeneous disease with widely disparate outcomes following standard therapy. DUSP22 and TP63 rearrangements may serve as predictive biomarkers to help guide patient management.

Melanocytic Matricoma: A Potential Mimic of Malignant Melanoma.

Melanocytic matricoma is a rare dermal tumor that typically presents on the sun-damaged skin of older patients. While there is controversy in the literature regarding the proper characterization of this tumor, there are certain histological and immunohistochemical features that have been described. This report presents a case of melanocytic matricoma with several unusual features that were initially feared to be malignant melanoma. Careful histologic and immunohistochemical analysis was required to rule out malignant melanoma and make the correct diagnosis. Given the rarity of melanocytic matricoma and the potential for it to mimic malignant melanoma, it is important for pathologists to keep melanocytic matricoma on the differential and be aware of the clinical, histological, and immunohistochemical features of this tumor.

Co-occurrence of Langerhans cell histiocytosis and Rosai-Dorfman disease: possible relationship of two histiocytic disorders in rare cases.

Rosai-Dorfman disease and Langerhans cell histiocytosis are both disorders of accessory immune cells. Two cases have been previously reported of concurrent Langerhans cell histiocytosis and Rosai-Dorfman disease. In this report, we characterize the findings and selected molecular studies in nine additional cases. Histology was reviewed. Immunohistochemical stains were performed on all cases in which slides or blocks were available. A combination of CD1a, S-100, CD3, CD20, langerin, CD68, CD163, CD21, CD35 and CD123 immunohistochemical stains were performed. High-resolution array comparative genomic hybridization was performed on six samples from five cases. In these cases, seven were female and two male, with an average age of 25 years (15 months-59 years). A majority of the cases were identified in lymph node. Areas of Langerhans cell histiocytosis had a typical appearance with the existence of bland 'coffee-bean' nuclei, clear cytoplasm and associated eosinophils. The immunophenotype was typical, including expression of CD1a, S100, CD68 and langerin. In areas of Rosai-Dorfman disease, there was emperipolesis seen in all cases. Cells were intermediate-large in size with large round nuclei and ample clear or pale cytoplasm. The lesional cells were positive for S100, CD68, CD163, without expression of langerin or CD1a. Array comparative genomic hybridization showed gains and/or losses in four of the six samples. One case showed no gains or losses and one additional case showed gains and losses in the Langerhans cell histiocytosis, while no abnormalities were discovered in the Rosai-Dorfman disease component. These findings are comparable to those seen in previous studies of Langerhans cell histiocytosis. We report the clinical and pathologic findings of the combination of Langerhans cell histiocytosis and Rosai-Dorfman disease. Furthermore, we suggest on the basis of evidence from our cases that, when simultaneous, the two entities may be pathophysiologically related.

Collagenous Gastritis in a Young Female With IgA Deficiency.

Collagenous gastritis, without colonic involvement, is exceptionally rare. It is not known to be associated with IgA deficiency and scleroderma. This is the first report of this type of association. We present a 26-year-old white female with a past medical history of gastroesophageal reflux disease and scleroderma. She was evaluated for complaints of abdominal pain and diarrhea. Esophagogastroduodenoscopy showed gastritis and duodenitis. Colonoscopy was normal. The histopathological report showed collagenous gastritis and focal lymphocytic duodenitis. A definitive treatment has not been established for this condition. Reporting such cases furthers understanding of the disease and will help to establish diagnostic criteria and to develop therapeutic strategies.

Expression of p63 protein in anaplastic large cell lymphoma: implications for genetic subtyping.

Anaplastic large cell lymphomas (ALCLs) are CD30-positive T-cell non-Hodgkin lymphomas that bear chromosomal rearrangements of the TP53 homologue TP63 in a subset of cases that demonstrate aggressive clinical behavior. In the present study, we examined the relationship between p63 protein expression by immunohistochemistry and the results of fluorescence in situ hybridization using TP63 probes in 116 ALCLs. We also determined the relative expression of full-length TAp63 and truncated ΔNp63 isoforms (eg, p40) in ALCL cell lines and a subset of clinical cases. Overall, 35.3% of ALCLs were positive for p63 protein. Primary cutaneous and anaplastic lymphoma kinase-negative ALCLs were positive more frequently than anaplastic lymphoma kinase-positive ALCLs (P=.0034). As previously reported, cases with TP63 gene rearrangements expressed p63 uniformly. p63 expression in nonrearranged cases was associated with extra copies of TP63 on 3q28 (P<.0001). Extra copies of TP63 correlated with extra copies of the DUSP22 locus on 6p25.3 (P<.0001). Results of immunohistochemistry, Western blotting, and RNA sequencing indicated that p63 expression in nonrearranged cases was entirely attributable to TAp63 isoforms. Taken together, these findings indicate that ALCLs without TP63 rearrangements may express TAp63 isoforms of p63 and that this expression is associated with extra copies of TP63, probably due to widespread genomic copy number abnormalities rather than focal gains. Immunohistochemistry for p63 in ALCL is not specific for TP63 rearrangements but is useful clinically as a screening test to select cases for further testing by fluorescence in situ hybridization. Immunohistochemistry for ΔNp63 (p40) is not informative in the evaluation of ALCL.

Morphologic Features of ALK-negative Anaplastic Large Cell Lymphomas With DUSP22 Rearrangements.

Systemic anaplastic large cell lymphomas (ALCLs) are classified into ALK-positive and ALK-negative types. We recently reported that ALK-negative ALCLs are genetically heterogenous. The largest subset, representing 30% of cases, had rearrangements of the DUSP22 locus. These cases had favorable outcomes similar to ALK-positive ALCL, and superior to other ALK-negative ALCLs. Here, we examined the morphologic features of these cases in more detail. First, we conducted blinded review of hematoxylin and eosin slides of 108 ALCLs from our previous study, scoring cases for the presence of 3 histologic patterns and 5 cell types. Cases then were unblinded and re-reviewed to understand these features further. DUSP22-rearranged ALCLs were more likely than other ALK-negative ALCLs to have so-called doughnut cells (23% vs. 5%; P=0.039), less likely to have pleomorphic cells (23% vs. 49%; P=0.042), and nearly always (95%) had areas with sheet-like growth (common pattern). To examine the reproducibility of these findings, we conducted blinded review of hematoxylin and eosin slides of 46 additional ALK-negative ALCLs using a 0 to 3 scoring system to predict likelihood of DUSP22 rearrangement, the results of which correlated strongly with subsequent findings by fluorescence in situ hybridization (P<0.0001). Although all ALCLs share certain morphologic features, ALCLs with DUSP22 rearrangements show significant differences from other ALK-negative ALCLs, typically showing sheets of hallmark cells with doughnut cells and few large pleomorphic cells. These morphologic findings and our previous outcome data suggest that ALK-positive ALCLs and DUSP22-rearranged ALCLs represent prototypical ALCLs, whereas ALCLs lacking rearrangements of both DUSP22 and ALK require further study.

Transformation of follicular lymphoma to Burkitt-like lymphoma within a single lymph node.

Aberrant expression of bcl-2 , caused by a t(14;18) translocation, is most commonly associated with follicular lymphoma. In a subset of these tumors, additional acquisition of a translocation involving c-myc leads to transformation to a high-grade lymphoma. We report a case of follicular lymphoma containing a t(14;18) translocation transforming into a Burkitt-like lymphoma containing the original t(14;18) as well as an additional t(8;14). The latter translocation resulted in the phenotype of Burkitt-like lymphoma, and the transformation from follicular lymphoma to Burkitt-like lymphoma was demonstrable within a single lymph node. To the best of our knowledge, this is the first report of a case documenting direct transformation of follicular lymphoma into Burkitt-like lymphoma in the same lymph node. This case illustrates the dramatic oncogenic stimulus that results from the inhibition of apoptosis by bcl-2 combined with the deregulation of cell growth by c-myc .

Nonseminomatous germ cell tumor arising in splenogonadal fusion.

Splenogonadal fusion is a rare congenital malformation in which the spleen is abnormally connected to the gonads or to the mesonephric derivatives. A few more than 150 cases have been described in the world literature. We report an additional case of splenogonadal fusion. A nonseminomatous germ cell tumor was found in the testicle involved in this splenogonadal fusion. To our knowledge, this is the third reported case of a testicular neoplasm associated with splenogonadal fusion and the first reported case of intra-abdominal nonseminomatous germ cell testicular tumor arising in this rare anomaly. The literature pertaining to splenogonadal fusion and the testicular tumor arising in this anomaly is briefly reviewed.

Mediastinal rhabdomyoma: a case report and review of the literature.

An incidental anterior-superior mediastinal rhabdomyoma is reported in a 68-year-old man who died of hypovolemic shock as a result of massive blood loss due to transection of aorta after being hit by a moving motor vehicle. This is the third reported case of mediastinal rhabdomyoma in the literature. The immunohistochemical evidence of expression of muscle-specific markers supports the rhabdomyomatous nature of this neoplasm, and electron microscopic demonstration of haphazardly arranged myofilaments with prominent Z bands, "jack-straws" in the mitochondria, and the absence of desmosomes is supportive of extracardiac origin of this rhabdomyoma. The possible histogenesis of extracardiac adult rhabdomyoma (EAR) in the anterior-superior mediastinum from the thymic myoid cells is also discussed.

Histopathological characterization of a Cameron lesion.

Cameron lesions are linear erosions located at the neck of a hiatal hernia (HH) in patients with a large HH. The prevalence has been seen in up to 5% of patients with HH who undergo esophagogastroduodenoscopy, and they can be associated with overt gastrointestinal bleeding or anemia. These lesions occur due to vascular compression by the diaphragm in a large sliding HH. Histopathologic changes seen in the biopsy tissue of a Cameron lesion are due to ischemia, but this ischemia is reversible with treatment of HH. The existence of this entity and the histopathologic picture of a Cameron lesion is not well known to pathologists, and therefore, a microscopic picture of a Cameron lesion can be easily confused with ischemic gastritis. Ischemic gastritis is the result of atherosclerosis, usually seen in older people, unrelated to HH, and is not easily reversible. The authors received a gastric biopsy of a hiatal hernia without any associated clinical diagnosis of a Cameron lesion conveyed to the pathologist. This biopsy tissue showed ischemic changes in the gastric mucosa on microscopic examination. Diagnosis of ischemic gastritis was considered but ruled out after the case was discussed with the gastroenterologist. The correct diagnosis was made once the clinical diagnosis of HH with Cameron lesion (ie, a vertical red erosion) was made known to the pathologist. By reporting this case, the authors aim to increase awareness of Cameron lesion among pathologists so that they ask about the presence of a Cameron lesion before making the diagnosis of ischemic gastritis.

Fuzeon-induced collagenophagic granuloma: a peculiar granulomatous injection site reaction to Fuzeon--a case report and review of literature.

Enfuvirtide (ENF, T-20, or Fuzeon [Hoffman-La Roche Inc, Nutley, NJ, and Trimeris, Inc, Durham, NC]) is an HIV-1 fusion inhibitor and is the only injectable antiretroviral drug available. Injection site reactions (ISRs) are the most frequently reported adverse events, occurring in about 98% of patients. A granuloma annulare-like granulomatous ISR has been reported. We report a granulomatous ISR that is different from granuloma annulare and granuloma annulare-like reaction because it is rich in multinucleated giant cells engulfing altered collagen. We call this type of ISR a collagenophagic granuloma. Most previous reports-with the exception of 1 report-about ISRs with ENF treatment have used punch biopsies, which lack the depth to analyze the reticular dermis and subcutaneous tissue and, therefore, may have missed ISRs, which look like granuloma annulare, and the collagenophagic granulomatous reaction.

Uterine cervical teratoma with divergent neuroepithelial differentiation and development of an oligodendroglioma: report of a case and review of the literature.

Teratomas of the uterine cervix are rare. Immature and malignant uterine cervical teratomas are extremely rare. A uterine cervical teratoma with divergent neuroepithelial differentiation and/or development of a neurological tumor has never been reported. We describe a case of uterine cervical teratoma exhibiting ectodermal, endodermal, mesodermal, and various types of neuroepithelial differentiation and development of a small oligodendroglioma in a 38-year-old female. The presence of immature neuroepithelium defines this teratoma as immature, and the development of a low-grade malignant neoplasm from one of its components makes it malignant. The pertinent literature is reviewed.

Primary Adenoidal Hodgkin's Disease: Report of a Case with an Unusual Morphology and Review of the Literature.

The nasopharyngeal lymphoid tissue (adenoids) is an uncommonly reported primary site for Hodgkin's disease. We report a case of primary adenoidal, interfollicular, epithelioid cell-rich variant of mixed cellularity Hodgkin's disease. The combination of an interfollicular pattern and richness of epithelioid histiocytes made it very difficult to make the diagnosis of Hodgkin's disease without the help of immunohistochemistry. To our knowledge, only 39 cases of Hodgkin's disease primarily involving the Waldeyer's ring have been reported in the English literature, 24 of these primarily involving the adenoids. Our case shows the difficulty encountered in making the diagnosis when a very unusual morphologic appearance of Hodgkin's disease is seen at a rare presentation site. The appropriate immunohistochemical work-up should be performed in unusual lymphohistiocytic proliferations involving the Waldeyer's ring. Int J Surg Pathol 8(3):241-246, 2000