Uterine Lithiasis associated with neoplasia in a female dog: case reportABSTRACT
Uterine lithiasis is an extremely rare condition in veterinary medicine, with few documented reports. This paper describes the case of a ten-year-old mixed-breed female dog presented with apathy, abdominal distension, and vaginal discharge. Laboratory and imaging examinations indicated open pyometra associated with the presence of a foreign body. During ovariohysterectomy, two pyramidal calculi were identified in the uterine lumen, along with rupture of the uterine horns and the presence of multiple nodules. Histopathological analysis confirmed a high-grade squamous cell carcinoma, while crystallographic analysis revealed that the calculi were primarily composed of struvite (magnesium ammonium phosphate hexahydrate) and carbonate apatite (carbonated calcium phosphate). The formation of the calculi was attributed to a chronically inflamed and alkaline uterine environment, exacerbated by infection and neoplasia. This case report expands the understanding of the pathogenesis of uterine lithiasis in dogs and underscores the need for further studies to better elucidate this condition. Additionally, it highlights the importance of spaying in preventing severe uterine disorders in female dogs.
Keywords:
uterolithiasis; squamous cell carcinoma; pyometra; uterine calculus
RESUMO
A litíase uterina é uma condição extremamente rara na medicina veterinária, com poucos relatos documentados. Este trabalho descreve o caso de uma cadela, sem raça definida, de 10 anos, atendida com quadro clínico de apatia, distensão abdominal e secreção vaginal. Exames laboratoriais e de imagem indicaram piometra aberta associada à presença de corpo estranho. Durante a ovário-histerectomia, foram identificados dois cálculos piramidais no lúmen uterino, além de ruptura dos cornos e presença de múltiplos nódulos. A análise histopatológica confirmou carcinoma de células escamosas de alto grau de malignidade, enquanto a análise cristalográfica revelou que os cálculos eram compostos majoritariamente por fosfato amônio magnesiano hexa-hidratado fosfato de cálcio carbonatado. A formação dos cálculos sugerida foi atribuída a um ambiente uterino cronicamente inflamado e alcalino, exacerbado pela infecção e pela neoplasia. Este relato amplia o conhecimento sobre a patogênese da litíase uterina em cães e destaca a necessidade de novos estudos para melhor elucidar essa condição. Além disso, destaca a relevância da castração na prevenção de alterações uterinas graves em fêmeas caninas.
Palavras-chave:
ureterolitíase; carcinoma de células escamosas; piometra; cálculo uterino
INTRODUCTION
Uterine calculus, uterine lithiasis, or uterolithiasis is a rare condition in humans and extremely rare in animals, having been described in a few women (Haddad, 1963; Alpert et al., 1990; Negussie and Kidane, 2013; Lindgren, 2018; Kumar et al., 2023; Sepúlveda et al., 2024) and in a single female dog (Iwasaki and Oliveira, 1991). Due to the scarcity of reports, its pathogenesis is not well understood. However, it has been more frequently observed in individuals with malignant or benign uterine neoplasms, chronic inflammatory processes (Alpert et al., 1990; Negussie and Kidane, 2013), and in those using intrauterine contraceptive devices, such as IUDs (Lindgren, 2018). Given the absence of reports of uterine lithiasis associated with neoplasia in female dogs, this study aims to describe the finding and compare it with the cases reported in humans and the only documented case of a uterine calculus in a dog.
ETHICAL ASPECTS
This research was not submitted to the Ethics Committee on Animal Use.
CASE REPORT
A 10-year-old, 24kg, intact mixed-breed female dog was presented to the outpatient clinic of the Equine and Integrative Health Research Group with a history of apathy, lethargy, anorexia, and abdominal distension (Fig. 1A). According to the owner, abdominal swelling and decreased appetite had been observed for approximately one month. The owner also denied any administration of contraceptive vaccines. On clinical examination, the dog presented with icteric mucous membranes, cardiac arrhythmia, abdominal pain, mucosanguineous vaginal discharge, and edema (Fig. 1B).
Hematological tests revealed microcytic hypochromic anemia, proteinuria (9.9mg/dL), dehydration, and marked leukocytosis characterized by neutrophilia and monocytosis).
A Patient with mildly icteric skin and abdominal distension. B - Patient with vulvar edema and mucosanguineous discharge.
The biochemical profile revealed markedly elevated levels of urea, creatinine, and alkaline phosphatase.
Abdominal ultrasonography showed free fluid (FF) in the abdominal cavity, a liver with heterogeneous texture and altered parenchyma, and a spleen with enlarged vessels. The uterus was enlarged with thickened walls (Fig. 2A) and distended by an anechoic content containing scattered hyperechoic punctate structures, consistent with pyometra. A foreign body measuring 2.79×1.91cm was also identified in the uterine region (Fig. 2B). The stomach and intestines appeared normal, while the kidneys, adrenal glands, and pancreas could not be visualized due to overlapping structure.
Abdominal radiographic examination revealed radiopaque structures in the uterine region, with dimensions larger than those observed on ultrasonography, measuring 5.7×3.5cm (Fig. 3).
Based on the conducted examinations, the main diagnostic hypothesis was open pyometra with uterine rupture, indicating the need for therapeutic ovariohysterectomy combined with exploratory laparotomy. During the surgical procedure, 4.8 liters of serosanguineous exudate with a foul odor were drained (Fig. 4A). A significant deposition of fibrin and the formation of adhesions between abdominal organs were also observed (Fig. 4B), which hindered the identification of the uterus.
A - Free fluid (FF) in the abdominal cavity; uterine body (UB) distended with irregular, thickened wall and anechoic content within its lumen. B - Pyramidal foreign body (FB) visualized through an acoustic window via the bladder (BL).
Abdominal radiograph of a female dog showing the presence of a foreign body in the uterine region.A - Ventrodorsal radiographic projection showing a triangular radiopaque area in the pelvic region. B - Left lateral radiographic projection showing a radiopaque area measuring 57.98mm by 35.28mm in the pelvic region.
A - Serosanguineous free fluid present in the abdominal cavity during exploratory laparotomy in a female dog. B - Presence of fibrin and adhesion in structures of the abdominal cavity.
After drainage of the free fluid and removal of adhesions, the uterine body was exteriorized, showing complete loss of the usual anatomy, with increased volume, multiple nodulations, friability, areas of necrosis, rupture of the uterine horns, and obstruction of the lumen due to the nodulations (Fig. 5A). During ovariohysterectomy, a sharp foreign body was identified in the uterine lumen. After its removal, mucopurulent content and two pyramidal-shaped calculi were observed (Figure 5B), measuring 3.5×4×2cm and 2.5×3×1.9cm, weighing 11.2g and 9.059g, respectivel.
A - Uterus with loss of usual anatomy, presence of nodulations, friable tissue, areas of necrosis, and rupture of the uterine horns.B - Pyramidal calculi present in the uterine cavity.
The ovariohysterectomy was completed, and the abdominal cavity was lavaged with 0.9% saline solution. After the procedure, the animal was reassessed, weighing 19kg. Samples of the nodulations were sent for histopathological analysis, resulting in a diagnosis of high-grade squamous cell carcinoma (SCC). One of the uterine calculi was sent for crystallographic analysis, revealing that its core was composed of 85% magnesium ammonium phosphate hexahydrate and 15% carbonate apatite, with a crystalline layer composed of 60% carbonate apatite and 40% magnesium ammonium phosphate hexahydrat (Fig. 6).
A Pyramidal calculi present in the uterine cavity, compared with a 40x12 needle. B - Result of the crystallographic analysis of the calculus.
Due to the reserved prognosis, due to open and ruptured pyometra associated with a severe septic condition and the malignancy of the carcinoma, the patient passed away seven days after the surgery.
DISCUSSION
The only reported case of uterine lithiasis in dogs in the literature was described in 1991, involving a seven-year-old female treated semi-annually with medroxyprogesterone (anti-heat vaccines). The dog presented with cystic endometrial hyperplasia and multiple uterine calculi ranging from 2 to 3 mm in diameter, composed of calcium, oxalate, phosphate, carbonate, and magnesium (Iwasaki and Oliveira, 1991). The authors suggested that the formation of the calculi was related to an initial inflammatory process, followed by fluid accumulation and subsequent mineral precipitation.
In the present study, it is considered that pyometra initially developed, favoring the onset of squamous cell carcinoma (SCC) or evolving concomitantly. Chronic infection and the presence of the tumor resulted in the loss of normal uterine anatomy due to tissue necrosis and the release of cellular debris, with subsequent accumulation of purulent secretion and exudate rich in plasma proteins in the uterine lumen. This chronically inflamed and alkaline environment, associated with the activity of urease-positive bacteria, may have favored the progressive formation of struvite (magnesium ammonium phosphate hexahydrate) and carbonate apatite, minerals similar to those described in the case of cystic endometrial hyperplasia by Iwasaki and Oliveira (1991).
In human medical literature, reports of uterine lithiasis are scarce and mostly associated with blood retention in the uterine lumen (hematometra), suggesting that the presence of blood may act as a predisposing factor for the formation of calculi (Sepúlveda et al., 2024). Surgical procedures, such as cesarean sections, have also been implicated in creating a microenvironment favorable to calcification (Sepúlveda et al., 2024). Moreover, chronic inflammatory processes, uterine neoplasms (Haddad, 1963; Alpert, 1990; Lidgren, 2018; Kumar et al., 2023), and the use of intrauterine contraceptive devices (Lidgren, 2018) have been described as conditions that may predispose to uterolith formation. Based on the previous findings, it is hypothesized that the formation of the uterine calculus in this case was triggered by chronic inflammatory and infectious processes related to pyometra and SCC. However, further studies are needed to precisely elucidate the pathogenesis of uterine lithiasis.
CONCLUSION
This report reinforces the rarity of uterine lithiasis in dogs and suggests that chronic inflammatory processes and neoplasms may play a central role in the formation of uterine calculi. The mineral composition of the observed calculi supports the hypothesis that inflamed and alkaline uterine environments favor crystal precipitation. Elucidating the mechanisms involved in the pathogenesis of uterine lithiasis still requires further investigations, aiming to expand the understanding of its pathogenesis and clinical implications. Additionally, it highlights the importance of spaying in preventing severe uterine disorders in female dogs.
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