Flatfishes are among the most strikingly asymmetrical vertebrates on Earth. During development, one eye migrates across the top of the skull so that both eyes and coloration end up on a single side, while the other side remains eyeless and pale. Currently, 826 species across 19 families are recognized as valid. In most flatfish families, eye position is fixed: families such as Paralichthyidae, Bothidae, and Scophthalmidae have both eyes on the left side, while families such as Pleuronectidae, Poecilopsettidae, and Samaridae have both eyes on the right. In contrast, members of Psettodidae, considered the most primitive flounders, naturally occur in roughly equal proportions with eyes on either side, and within Citharidae eye orientation varies at the generic level.

For decades, reversed individuals—those with eyes on the side opposite to their family’s norm—had never been documented in the family Bothidae, as summarized by researchers in 1964 and 1983. The family was long regarded as the most specialized group within the order Pleuronectiformes, with pronounced left-right differences such as a lateral line developed only on the eyed side and a much longer pectoral fin on the eyed side than on the blind side. This high degree of asymmetry led scientists to consider that the lower the level of specialization, the more likely inversion phenomena are to occur. Reversal was reported most frequently in Paralichthyidae and Pleuronectidae, families with fixed eye positions but lower degrees of asymmetrical development.

That assumption has now been shaken. In recent years, three reversed bothid specimens have been found and reported in the genera Chascanopsetta, Parabothus, and Crossorhombus. The two new specimens from Taiwan, belonging to Engyprosopon maldivense and Engyprosopon grandisquama, represent the first records of the reversed condition among members of their genus. Moreover, both show reversed internal organs—a condition known as situs inversus—making them the third and fourth records of visceral inversion in the entire family Bothidae.

The first specimen, a male Engyprosopon maldivense measuring 82.3 millimeters in standard length, was collected off Ke-Tzu-Liao Fishing port in Kaohsiung, southern Taiwan, in February 2024. The second, a female Engyprosopon grandisquama measuring 51.4 millimeters, was collected from the same waters in May 2024. Both were preserved in the Pisces Collection of the National Museum of Marine Biology and Aquarium in Pingtung, Taiwan. Detailed examination, including digital radiographs taken in collaboration with the Hokkaido University Museum in Japan, allowed researchers to compare the reversed individuals with normal specimens collected from the same location.

The reversed Engyprosopon maldivense was identified based on several diagnostic features: the absence of blotches on the caudal fin, no serrations on the inner gill rakers, biserial upper-jaw teeth, a wide interorbital width, 44 lateral-line scales, and 0 + 9 gill rakers. Its meristic and morphometric data generally agree with those of normal sinistral specimens, with only minor differences such as a slightly larger lower eye and slightly different jaw and pelvic-fin proportions. The reversed Engyprosopon grandisquama was identified by a pair of black blotches on the caudal fin, 40 lateral-line scales, 0 + 7 gill rakers, and a distinctive interorbital width. In both specimens, the liver is situated on the eyed side and a large part of the stomach on the blind side—a complete reversal of visceral organ positions compared with normal individuals.

Previously, reversed specimens in the family Bothidae were extremely rare, with only three reported cases. The rarity is possibly due to their low commercial value, which results in a low chance of detecting an inversion. Bothidae and Samaridae are generally small, contain few species important to fisheries, and are mostly discarded or used as feed for other fish. In contrast, reversal is most commonly reported in Pleuronectidae and Paralichthyidae, which contain many species important to fisheries. Abnormal individuals with both eyes on the opposite side are easily discovered during the distribution process of these fish, and when processed into dried fish, many individuals of the same species are lined up, making inverted individuals highly conspicuous. From this, it can be speculated that the observed frequency of inverted individuals is due to differences in the chances of discovery rather than true biological differences among families.

The genetic basis of reversal has been demonstrated through crossbreeding experiments in the starry flounder Platichthys stellatus, conducted by Policansky in 1982. In Japanese populations, 100 percent of individuals have both eyes on the left side, whereas in American populations 50 percent have both eyes on the right and 50 percent on the left. Crossbreeding experiments between left-eyed males and females and between right-eyed males and females revealed that inverted individuals appeared at a rate of approximately 13 to 18 percent in both cases, confirming that the appearance of inversion is caused by heredity. The survival percentage of inversions occurring in nature is thought to be significantly lower than that observed in experimental results.

Reproduction in Bothidae may impose additional constraints on reversed individuals. It is known that reproductive behavior involves males and females overlapping away from the seabed. If the position of the genital pores is reversed, there would be a disadvantage during mating, which could explain a geographical bias in the frequency of reversal similar to that seen in Platichthys stellatus, where the dextral type occurs predominantly on the American side and the sinistral type on the Japanese side.

The discovery of inverted individuals in three genera and four species of the family Bothidae has called into question the long-held idea that the family was too specialized for reversal to occur. The two new specimens from Taiwan suggest that the reversed condition in Bothidae may be more common than previously thought, and that the observed rarity reflects sampling bias rather than evolutionary constraint. As more specimens are examined and more collections are made in understudied waters, scientists may find that reversed flatfishes are quietly swimming throughout the world’s oceans, waiting to be noticed.

Subject of Research: Marine Biology

Article Title: First records of two reversed flatfishes, Engyprosopon maldivense and Engyprosopon grandisquama ( Actinopterygii , Pleuronectiformes , Bothidae ), from Taiwan, northwestern Pacific Ocean

Article References: Amaoka, K., Hо, H.-C., & Su, Y. (2026). First records of two reversed flatfishes, Engyprosopon maldivense and Engyprosopon grandisquama (Actinopterygii, Pleuronectiformes, Bothidae), from Taiwan, northwestern Pacific Ocean. Acta Ichthyologica et Piscatoria, 56, 431-439. https://doi.org/10.3897/aiep.56.207218

Image Credits: AI Generated

DOI: 10.3897/aiep.56.207218

Keywords: flatfish, Engyprosopon, Taiwan, situs inversus, Bothidae, reversal, marine biology, First, records, reversed, flatfishes, maldivense

Situs inversus totalis is a congenital condition in which the major visceral organs are reversed from their normal positions along the left-right axis. The liver comes to lie predominantly on the left, the stomach and spleen shift to the right, and the cardiac apex points rightward, a configuration called dextrocardia. Estimates of its prevalence vary, but the condition is generally thought to affect roughly one in ten thousand individuals, and many carriers live their entire lives unaware of their mirrored anatomy. The condition arises during embryogenesis, when the normally stereotyped left-right patterning of the developing embryo is globally reversed. A landmark study by Nonaka and colleagues, published in Nature in 2002 and cited in the report’s reference list, demonstrated in the mouse embryo that the directional flow of fluid across the node, the embryonic organizer structure, is sufficient to determine left-right patterning, and that artificially reversing this flow reverses organ situs. Motile cilia at the node generate this leftward current, and defects in ciliary function underlie many cases of laterality disorders, including both situs inversus and the more chaotic arrangement known as heterotaxy.

As Sutherland and Ware summarized in their 2009 review of disorders of left-right asymmetry, the clinical significance of situs anomalies lies less in the mirroring itself than in its associations. Pure situs inversus totalis, in which the reversal is complete and orderly, is frequently an incidental finding discovered on imaging performed for unrelated complaints. Heterotaxy, by contrast, involves ambiguous or discordant organ positioning and is strongly associated with congenital heart disease and other malformations. A hospital-based study by Chen and colleagues published in Birth Defects Research in 2020 examined comorbidities in patients with situs inversus totalis and documented the range of conditions that accompany the mirrored anatomy in hospital populations. Clinicians must also contend with the practical consequences of reversed anatomy: physical examination findings are transposed, electrocardiograms require lead reversal for correct interpretation, appendicitis presents with left-sided pain, and surgical approaches must be rethought from first principles.

Into this already unfamiliar anatomical landscape, the Japanese team’s patient added a second layer of complexity. The case involves a patient found to have massive splenomegaly, an abnormal enlargement of the spleen, in the setting of malignant lymphoma, a cancer of the lymphatic system. The keywords attached to the published article situs inversus, malignant lymphoma, and splenomegaly capture the three threads of the story. In a body with normal organ arrangement, an enlarged spleen occupies the left upper quadrant of the abdomen and can be identified by its characteristic shape, its relationship to the ribs and stomach, and its homogeneous tissue density on computed tomography or ultrasound. In a patient with situs inversus totalis, the spleen resides on the right, and when it grows to enormous size it can extend across the midline, displace neighboring structures, and present an imaging appearance that mimics other organs.

The central image that gives the report its title shows a spleen so enlarged and so altered in texture that it resembled liver parenchyma. The phrase liver-like spleen refers to this visual deception: on cross-sectional imaging, the organ’s density and architecture appeared more like hepatic tissue than like the typical spleen. For clinicians evaluating a patient with reversed anatomy and a large right-sided or midline abdominal mass, distinguishing an enormously enlarged spleen from a displaced or accessory liver lobe, a tumor, or an abnormal collection of fluid is not a trivial exercise. The authors’ acknowledgment section thanks Dr. Ken Sadahira and Dr. Mikio Okayama for their assistance in patient care, indicating that the case was managed by a clinical team rather than observed from afar. The report also notes that no datasets were generated or analyzed, consistent with its format as a clinical image publication rather than a research study.

The association between lymphoma and the spleen is well established. The spleen is a lymphoid organ, and lymphomas, which arise from lymphocytes, frequently involve it. Splenomegaly in lymphoma may reflect direct infiltration by malignant cells, congestion, or reactive changes, and an enlarged spleen can itself be the presenting sign that brings a patient to medical attention. Trautner and colleagues, in a 2010 report in Clinical Nuclear Medicine cited by the Japanese authors, described the additional value of hybrid imaging in a patient with newly diagnosed lymphoma who also happened to have situs inversus totalis, underscoring that this combination of mirrored anatomy and hematologic malignancy, while rare, recurs often enough in the literature to merit attention. When the two coincide, the diagnostic radiologist must interpret every image against a reversed anatomical template, and subtle findings can be misassigned to the wrong organ.

Eitler, Bibok, and Telkes, writing in the International Journal of General Medicine in 2022, provided a clinical review of situs inversus totalis that frames the practical stakes. They emphasized that while most affected individuals are asymptomatic, the condition demands vigilance in diagnostic reasoning, surgical planning, and the interpretation of imaging studies. Their review, together with the earlier genetic and epidemiological work cited in the present case report, forms the scholarly backdrop against which the Kawasaki team’s images should be read. The report’s contribution is not a new therapy or a genetic discovery but a vivid demonstration of how far normal anatomical assumptions can mislead even experienced clinicians when the underlying blueprint is mirrored and then distorted by disease.

The publication process itself reflects the case’s timeline. According to the article’s record, the manuscript was received on 1 April 2026, accepted on 24 September 2026, and published on 1 October 2026 in the Journal of General Internal Medicine, the flagship journal of the Society of General Internal Medicine. All three authors are affiliated with Kawasaki Municipal Kawasaki Hospital in Kanagawa, Japan, with Okamoto based in the Department of Hematology and Miyaki and Kamiya in the Department of Internal Medicine, Kamiya holding appointments in both departments. Miyaki wrote the initial draft of the manuscript, and all authors had access to the data and helped revise the intellectual content. The authors declared no conflicts of interest and received no funding for the work. Correspondence for the article is directed to Takahiro Kamiya, whose ORCID identifier is listed in the publication record.

Why should a single clinical image merit attention beyond the ward? The answer lies in the pedagogical power of the exceptional case. Medical education proceeds in part through pattern recognition, and patterns are learned from typical presentations. But diagnostic error frequently occurs at the boundaries, where rare anatomy, rare disease, and rare combinations interact. A liver-like spleen in a patient with situs inversus totalis is precisely such a boundary case. It reminds radiologists that organ identification rests on more than position and density, that clinical history and correlative imaging are indispensable, and that the mirrored body can transform familiar signs into unfamiliar configurations. For internists and hematologists, it reinforces the point that splenomegaly in lymphoma can reach sizes and textures that confound standard heuristics.

The case also connects to one of the most elegant stories in developmental biology. The discovery that cilia-driven nodal flow sets the left-right axis, confirmed by the artificial flow experiments in mice, transformed laterality disorders from a descriptive curiosity into a mechanistically understood class of conditions. Every patient with situs inversus totalis carries in their anatomy the fossil record of that embryological decision, reversed at its origin. When disease such as lymphoma then remodels the reversed organs, clinicians are asked to read two overlapping stories at once: the congenital mirror and the acquired pathology. The image published by Miyaki, Okamoto, and Kamiya captures that intersection in a single frame, a spleen grown so large and altered that it borrowed the appearance of its mirrored neighbor, the liver. For the general reader, it is a striking reminder that human anatomy, even at its most orderly, holds surprises, and that medicine’s textbooks are at best maps of the average, to be consulted with humility whenever an individual patient departs from it.

Subject of Research: Splenomegaly resembling liver tissue in a patient with situs inversus totalis and malignant lymphoma

Article Title: A Liver-like Spleen in Situs Inversus Totalis

Article References: Miyaki, Y., Okamoto, S., & Kamiya, T. (2026). A Liver-like Spleen in Situs Inversus Totalis. Journal of General Internal Medicine. https://doi.org/10.1007/s11606-026-10873-x

Image Credits: AI Generated

DOI: 10.1007/s11606-026-10873-x

Keywords: situs inversus, splenomegaly, malignant lymphoma, clinical imaging, left-right asymmetry, dextrocardia, heterotaxy, nodal cilia, hematology, diagnostic radiology, congenital anatomy, case report