T‐cell‐derived Hodgkin lymphoma has motility characteristics intermediate between Hodgkin and anaplastic large cell lymphoma

Classic Hodgkin lymphoma (cHL) is usually characterized by a low tumour cell content, derived from crippled germinal centre B cells. Rare cases have been described in which the tumour cells show clonal T‐cell receptor rearrangements. From a clinicopathological perspective, it is unclear if these cases should be classified as cHL or anaplastic large T‐cell lymphoma (ALCL). Since we recently observed differences in the motility of ALCL and cHL tumour cells, here, we aimed to obtain a better understanding of T‐cell‐derived cHL by investigating their global proteomic profiles and their motility. In a proteomics analysis, when only motility‐associated proteins were regarded, T‐cell‐derived cHL cell lines showed the highest similarity to ALK⁻ ALCL cell lines. In contrast, T‐cell‐derived cHL cell lines presented a very low overall motility, similar to that observed in conventional cHL. Whereas all ALCL cell lines, as well as T‐cell‐derived cHL, predominantly presented an amoeboid migration pattern with uropod at the rear, conventional cHL never presented with uropods. The migration of ALCL cell lines was strongly impaired upon application of different inhibitors. This effect was less pronounced in cHL cell lines and almost invisible in T‐cell‐derived cHL. In summary, our cell line‐derived data suggest that based on proteomics and migration behaviour, T‐cell‐derived cHL is a neoplasm that shares features with both cHL and ALCL and is not an ALCL with low tumour cell content. Complementary clinical studies on this lymphoma are warranted.     

Removal,early hand rearing,and successful reintroduction of an orangutan (Pongo pygmaeus pygmaeus/x abelii) to her mother

A newborn orangutan was removed from her mother 55 h after birth because no nursing had been observed. She was hand reared in a nursery for 3 d and then successfully reintroduced to her mother. Several factors that may have contributed to the successful reintroduction are discussed.     

Ki-1-positive anaplastic large cell lymphoma initially diagnosed as Hodgkin's disease by fine needle aspiration (FNA) cytology

A 45-year-old male presented with a large mass in the left axilla. FNA cytology was interpreted as Hodgkin's disease (HD), lymphocyte depletion (LD) type, but histopathologic and immunohistochemical examination showed features of Ki-1-positive anaplastic large cell lymphoma. Unrepresentative sampling by the FNA from the tumour periphery resulted in a false impression of dual reactive and neoplastic cell populations. which together with the frequent Reed-Sternberg-like cells led to the initial erroneous impression of HD. Therefore, the cytologic diagnosis of HD, LD should be approached with caution.     

Chromosome studies in the orangutan (Pongo pygmaeus): Practical applications for breeding and conservation

The unequivocal identification of Bornean, Sumatran, and first-generation hybrid orangutans can be carried out by chromosome analysis, a procedure that is more reliable than any other so far used to distinguish between orangutan subspecies. Chromosome differences between subspecies have been compared with protein and DNA studies, and these have shown that Bornean and Sumatran orangutans are more different from each other than we originally thought. Chromosome studies in the orangutan have shown variant chromosome types that are not subspecies-specific. One of these variant types is a product of a complex double inversion rearrangement and is a polymorphic trait in both subspecies. In view of our findings, specific guidelines have been recommended for evaluating the fertility of hybrid specimens and maintaining purebred orangutan stocks.     

Lipoid pneumonia in an orangutan (Pongo abelii) with chronic respiratory problems

An orangutan (Pongo abelii) presented with chronic respiratory problems. Cytological evaluation of the bronchoalveolar lavage fluids revealed macrophages with well‐circumscribed intracytoplasmic clear vacuoles and lipid droplets in the background, confirmed by Oil Red O staining. The findings were indicative of lipoid pneumonia. This is the first report of lipoid pneumonia in an orangutan.     

Facultative terrestrial hand postures in an orangutan (Pongo pygmaeus) and pongid evolution

An adult male orangutan at the Chicago Zoological Park utilizes various knuckle-walking hand postures in terrestrial bipedal-squatting and quadrupedal diagonal-sequence, diagonal-couplet gaits. A study was conducted in order to discern the circumstances surrounding the subject's terrestrial locomotor modes. It was found that various locomotor behaviors correlate with specific conditions of the substrate and the subject's motivation. Biomechanical properties of orangutan knuckle-walking are discussed in terms of their relevance for modelling hominoid phylogeny.     

Developmental changes in the facial morphology of the Borneo orangutan (Pongo pygmaeus): possible signals in visual communication

Orangutans display remarkable developmental changes and sexual differences in facial morphology, such as the flanges or cheek-pads that develop only on the face of dominant adult males. These changes suggest that facial morphology is an important factor in visual communication. However, developmental changes in facial morphology have not been examined in detail. We studied developmental changes in the facial morphology of the Borneo orangutan (Pongo pygmaeus) by observing 79 individuals of various ages living in the Sepilok Orangutan Rehabilitation Centre (SORC) in Malaysia and in Japanese zoos. We also analyzed photographs of one captive male that were taken over a period of more than 16 years. There were clear morphological changes that occurred with growth, and we identified previously unreported sexual and developmental differences in facial morphology. Light-colored skin around the eyes and mouth is most prominent in animals younger than 3 years, and rapidly decreases in area through the age of approximately 7 years. At the same time, the scattered, erect hairs on the head (infant hair) become thick, dense hairs lying on the head (adult hair) in both sexes. The results suggest that these features are infant signals, and that adult signals may include darkened face color, adult hair, whiskers, and a beard, which begin to develop after the age of approximately 7 years in both sexes. In females, the eyelids remain white even after 10 years, and turn black at around the age of 20; in males, the eyelids turn black before the age of 10. The whiskers and beards of adults are thicker in males than in females, and are fully developed before the age of 10 in males, while they begin to develop in females only after approximately 20 years. White eyelids and undeveloped whiskers and beards may be visual signals that are indicative of young adult females. Our results also show that the facial morphology of the unflanged male is similar to that of the adult female, although it has also been pointed out that unflanged males resemble younger individuals.     

Antineoplastic activity of the DNA methyltransferase inhibitor 5-aza-2′-deoxycytidine in anaplastic large cell lymphoma

DNA methylation is an epigenetic mechanism establishing long-term gene silencing during development and cell commitment, which is maintained in subsequent cell generations. Aberrant DNA methylation is found at gene promoters in most cancers and can lead to silencing of tumor suppressor genes. The DNA methyltransferase inhibitor 5-aza-2′-deoxycytidine (5-aza-CdR) is able to reactivate genes silenced by DNA methylation and has been shown to be a very potent epigenetic drug in several hematological malignancies. In this report, we demonstrate that 5-aza-CdR exhibits high antineoplastic activity against anaplastic large cell lymphoma (ALCL), a rare CD30 positive non-Hodgkin lymphoma of T-cell origin. Low dose treatment of ALCL cell lines and xenografted tumors causes apoptosis and cell cycle arrest in vitro and in vivo. This is also reflected in genome-wide expression analyses, where genes related to apoptosis and cell death are amongst the most affected targets of 5-aza-CdR. Furthermore, we observed demethylation and re-expression of p16^INK4A after drug administration and senescence associated β-galactosidase activity. Thus, our data provide evidence that 5-aza-CdR is highly efficient against ALCL and warrants further clinical evaluation for future therapeutic use.     

Perineal repair of a full‐thickness rectal prolapse in a wild Sumatran orangutan (Pongo abelii)

A Delorme's procedure perineal surgical repair was performed in a wild adult male Sumatran orangutan (Pongo abelii) with a chronic persistent rectal prolapse that had been unsuccessfully treated by 6 previous surgeries. The rectal prolapse did not recur, and the orangutan was successfully released to the wild, 6 weeks later.     

Dissociation of cortisol and behavioral indicators of stress in an orangutan (Pongo pygmaeus) during a computerized task

Computerized testing can induce behavioral signs of frustration in apes. Three variations of a computer task were used to investigate the effects of inter-trial intervals and rate of cursor movement on frustrative behavior and cortisol in an orangutan. Behaviors were recorded during test sessions, and saliva was collected immediately after test sessions for cortisol assay. Behavioral results indicated that extended (20 sec) periods of delay between trials induced signs of frustration in the subject, including forceful manual manipulation of objects and self-scratching. However, cortisol results indicated that Hypothalamic-Pituitary-Adrenal (HPA) axis activity was not induced by task performance. Rather, cortisol levels were reduced during performance of computer tasks compared to baseline levels. Findings from this study suggest that behavioral and cortisol responses to stress induced by performance of computer testing can become dissociated. This study validates salivary cortisol as a measure of HPA activity in apes and demonstrates a normal circadian rhythm of cortisol release in an orangutan.     

Light and scanning electron microscopic observations of the long hair of an orangutan (Pongo pygmaeus) with trisomy 22

Hair samples of a female orang-utan (Pongo pygmaeus) suffering from Trisomy 22 and three healthy orang-utans had been investigated in regard of their resilience, colour, medulla, cross sectional view, shaft diameter and cuticula structure. There were no characters noticed concerning the orang's hair with Trisomy only. The remarkable sex-specific differences found out in hair shaft diameters have been interpreted as a manifestation of the considerable sexual-dimorphism in orang-utans. The hair samples of all four individuals contain some with an anomaly of the cuticula-structure, which may be seen as an expression of the not species-specific environment in zoos.     

Hypothesis for the causes and periodicity of repetitive linear enamel hypoplasia in large, wild African (Pan troglodytes and Gorilla gorilla) and Asian (Pongo pygmaeus) apes

Repetitive linear enamel hypoplasia (rLEH) is often observed in recent large-bodied apes from Africa and Asia as well as Mid- to Late Miocene sites from Spain to China. The ubiquity and periodicity of rLEH are not understood. Its potential as an ontogenetic marker of developmental stress in threatened species (as well as their ancient relatives) makes rLEH an important if enigmatic problem. We report research designed to show the periodicity of rLEH among West African Pan troglodytes (12 male, 32 female), Gorilla gorilla (10 male, 10 female), and Bornean and Sumatran Pongo pygmaeus (11 male, 9 female, 9 unknown) from collections in Europe. Two methods were employed. In the common chimpanzees and gorillas, the space between adjacent, macroscopically visible LEH grooves on teeth with two or more episodes was expressed as an absolute measure and as a ratio of complete unworn crown height. In the orangutans, the number of perikymata between episode onsets, as well as duration of rLEH, was determined from scanning electron micrographs of casts of incisors and canines. We conclude that stress in the form of LEH commences as early as 2.5 years of age in all taxa and lasts for several years, and even longer in orangutans; the stress is not chronic but episodic; the stressor has a strong tendency to occur in pulses of two occurrences each; and large apes from both land masses exhibit rLEH with an average periodicity of 6 months (or multiples thereof; Sumatran orangutans seem to show only annual stress), but this needs further research. This is supported by evidence of spacing between rLEH as well as perikymata counts. Duration of stress in orangutans averages about 6 weeks. Finally, the semiannual stressor transcends geographic and temporal boundaries, and is attributed to regular moisture cycles associated with the intertropical convergence zone modified by the monsoon. While seasonal cycles can influence both disease and nutritional stress, it is likely the combination of seasonal variation in fruiting cycles with specific stressors (malaria and/or intestinal parasites, especially hookworm) that results in this widespread phenomenon. This seasonal stress is sufficiently common and of long duration (6 weeks on average in orangutans) that we think rLEH may reflect significant stress in recent and, inferentially, fossil apes. Increasing seasonality may have impinged negatively on later Miocene apes, especially if they lacked a clear birth peak or seasonality in their reproductive cycles.     

Fatal primary diffuse large B‐cell lymphoma of the maxillary sinus initially treated as an infectious disease in an elderly patient: A clinicopathologic report

Objective

To report a case of primary diffuse large B‐cell lymphoma (DLBCL) of the maxillary sinus in an 82‐year‐old Caucasian woman.

Background

Diffuse large B‐cell lymphoma of the maxillary sinus has non‐specific signs and symptoms that may be confused with benign inflammatory conditions and upper respiratory infections.

Methods

An incisional biopsy was performed. CD20⁺/CD3^–/Ki‐67: 95% cells were observed.

Conclusion

A good medical history, clinical and imaging evaluations and immunohistochemical reactions are crucial to establish a correct and early diagnosis of DLBCL.     

Discovery of 7-azaindole based anaplastic lymphoma kinase (ALK) inhibitors: Wild type and mutant (L1196M) active compounds with unique binding mode

We have identified a novel 7-azaindole series of anaplastic lymphoma kinase (ALK) inhibitors. Compounds 7b, 7m and 7n demonstrate excellent potencies in biochemical and cellular assays. X-ray crystal structure of one of the compounds (7k) revealed a unique binding mode with the benzyl group occupying the back pocket, explaining its potency towards ALK and selectivity over tested kinases particularly Aurora-A. This binding mode is in contrast to that of known ALK inhibitors such as Crizotinib and NVP-TAE684 which occupy the ribose binding pocket, close to DFG motif.