Human penile ossification is a rare urological condition with about 40 cases reported in the literature. While bone is essential for penetrative intercourse in many non-human mammals, human penile ossification appears to be part of a metaplastic process occurring after injury or trauma. Conditions such as Peyronie’s disease, diabetes mellitus, local trauma, and end-stage renal disease have been associated with this entity Human penile ossification may be asymptomatic or may be associated with previous trauma to the penis, or could on rare occasions be congenital. Ossification of the penis may be asymptomatic or may present with a lump in the penis, pain in the penis, or pain and curvature of penis in association with erection. Radiology imaging does demonstrate the ossification within the penis and complete excision of the ossification area of the penis tends to be associated with resolution of the symptoms. In the rare situation of osteosarcoma of the penis, surgical excision of the entire lesion does constitute an appropriate treatment.

Belshoff et al. [1] stated the ensuing:

• Human penile ossification is a rare urological condition with about 40 pathologically confirmed cases reported in the medical literature up to the time of publication of their article in 2021. [2] [3] [4] [5] [6] [7] [8] [9]. 
• While this is typically an acquired condition, there had been one documented congenital case, which had involved a five-year-old boy who had other genitourinary defects [2]. 
• Pathological calcification occurs through heterotopic mineralization of the penile soft tissues and had been associated with end-stage renal disease, diabetes mellitus, trauma, malignancy, and calcium dysregulation [3] [4] [5]   
• Nevertheless, the triggering mechanism was not entirely understood. 
• Historically, ossification of the penis had been presumed to be of vestigial origin due to the presence of penile bone in other animals, which facilitates reproduction [6] 
• Other people had challenged this postulate, favouring instead a primarily metaplastic process sustained by fibrosis [7] [8].
• The condition that had been most commonly associated with penile ossification is Peyronie’s disease. 
• This condition is typified by the development of fibrous penile scar tissue, resulting in curvature and painful intercourse, which might preclude sexual function. 
• Surgical reconstruction is often necessary in order to restore sexual function. 
• These surgical procedures include penile straightening through the use of tunica albuginea plication sutures, or partial excision of the scar with grafting into the tunica defect, among others [10]. 
• Significant penile ossification in this setting does represent a unique challenge for the reconstructive urologist [9]. 

Considering the rarity of penile ossification, it would be envisaged that majority of clinicians globally and well as most patients globally would not be familiar with the fact that bone or ossification could on rare occasions be found within the penis and they would tend not to be familiar with the manifestation, diagnosis, management and outcome of penile ossification. The ensuing article on penile ossification or bone tissue within the penis is divided into two parts: (A) Overview which has discussed general overview aspects of penile ossification, and (B) Miscellaneous narrations and discussions from some case reports, case series and studies related to penile ossification. 

Aim

To review and update the literature on bone or ossification within the human penis.

Methods 

Internet data bases were searched including Google; Google Scholar; Yahoo; and PUBMED. The search words that were used included: Bone in penis; penile ossification; OS Penis; and Penile OS. Fifty-seven (57) references were identified which were used to write the article which has been divided into two parts: 

[A] OVERVIEW 

Definition and General Statements [11] 

• Heterotopic bone within the penis is stated to be most commonly found in the elderly and in children. [12] [13] The presence of os penis in man is very rare Up the time of publication of their article, only 11 cases had been published. A close study of these cases shows their extreme heterogeneity. We think that the os penis should be considered as a heterotopic bone structure similar to that found in the animal world. To confirm this, they had presented their personal case study. 
• It had been pointed out that male mammals with the exception of Chimpanzees and human beings have intra-penile bone which is referred to as bacula. 
• It has also been iterated that, human beings, do have an equivalent of strong distal ligament within the glans penis. [14] 

Terminology

• It has been iterated that heterotopic bone within the penis is also referred to as baculum penis and also penile bone.[11]

Aetiology

The ensuing summations had been made regarding the aetiology of bone in the penis: [11] 

• Ossification of the penis could occur pursuant to trauma or injury to the penis. [15] 
• Ossification of penis had also been noted to be associated with diabetes mellitus, gout, venereal diseases, Peyronie’s disease, as well as neoplasia. 
• It has also been iterated that ossification of the penis had on rare occasions been congenital developments of penile ossification [2] 

Presentation

• Some of the possible presentations of ossification within the penis include: incidental finding upon radiology imaging for something else; curvature of penis upon erection; painful penis upon coital activity; and the finding of a lump within the penis with or without a history of trauma to the penis in the past, diabetes mellitus, and gout. 

Clinical Assessment Findings 

• Clinical examination of the penis may demonstrate normal findings, tender spot in the penis, curvature of penis upon erection, a lump palpable within the penis and on rare occasions a possible ulcer on the penis in association with a lump or tenderness in the penis. 

Miscellaneous Laboratory Investigations 

Urine

• Generally, in majority of cases of either heterotopic ossification of penis and osteosarcoma of the penis, the results of urinalysis, urine microscopy and urine culture would tend to be normal; nevertheless, urine examination tends to be part of general assessments of patients and if the scenario of a rare case of urinary tract infection, the infection would be appropriately treated to improve the general condition of the patient. 

Blood tests

Haematology blood tests

• Full blood count tends to be part of the general assessment of patients who have ossification of the penis and usually the results would tend to be normal. 

Biochemistry blood tests

• Some of the blood tests that tend to be undertaken in the assessment of patients who have ossification of the penis include: CRP, Bone profile, serum urea and electrolytes, eGFR, liver function, parathyroid function tests, and serum urate and usually in majority of cases the results would tend to be normal. 

Plain X-ray 

• Plain x-ray of the penis could demonstrate opacification within the penis, the site and size as well as number of the opacifications. 

Ultrasound Scan 

• Ultrasound scan of penis would demonstrate opacification within the penis, the site and size as well as number of the opacifications.

Computed Tomography (CT) scan 

• CT scan of penis would demonstrate opacification within the penis, the site and size as well as number of the opacifications.

Magnetic Resonance Imaging (MRI) scan 

• MRI scan of penis would demonstrate opacification within the penis, the site and size as well as number of the opacifications.

Treatment

• Small opacifications could be left alone or treated conservatively or expectantly. 
• Complete excision of the site of ossification and surgery to correct the curvature of the penis tends to provide effective treatment 

Pathology Examinations 

• Pathology examination of the specimen of the excised ossification lump from the penis does demonstrate features of the bony ossification with no evidence of inflammation; nevertheless, in cases of osteosarcoma of the penis features that demonstrate the tumour would be demonstrated as well as if the edges of the excised lesion are free of tumour. 

Differential Diagnosis 

• Ossification within the Corpora Cavernosa. [16] is a differential diagnosis of heterotopic ossification of the penis. 

Outcome 

• Generally, the outcome of excision of penile ossification has been good. 

[B] Miscellaneous Narrations And Discussions From Some Case Reports, Case Series, And Studies Related To Bone Within The Penis 

Belshoff et al [1] reported a 65-year-old man who was referred to their urology department for an eight-year history of dorsal curvature of his penis with erections. He had described a near 90-degree curvature, which had been stable for several years and was refractory to in-office verapamil injections. He did not have any difficulty obtaining erections; nevertheless, they were painful and bothersome. He found sexual intercourse to be also difficult and painful for both him and his partner due to the curvature. His medical and surgical history was otherwise unremarkable. Upon his examination, his penis was uncircumcised with a palpable, firm plaque along the dorsal aspect of his midshaft of penis measuring about 2.5 cm by 1.5 cm. A penile Doppler ultrasound was undertaken, which demonstrated a broad, linear, sheet-like densification of the dorsal tunica albuginea extending from the base of the penis along most of the shaft, predominantly along the right side (see figure 1).

                                              Figure 1: Penile Doppler ultrasound imaging demonstrating a 2.5-cm dorsal density with acoustic shadowing

A) Longitudinal view of the right corpora. B) Transverse view primarily of the right corpora Reproduced from [1] under the Creative Commons Attribution License In view of the extensive degree of plaque and the impact upon his quality of life, he was taken to the operating theatre for partial excision and grafting. Intraoperatively, the large, firm ossified plaque was immediately visualised, and care was taken to excise this while preserving the neurovascular bundles. The corporal defect was closed utilising a bovine pericardial graft (Coloplast, Minneapolis, MN). Upon intraoperative induction of an artificial erection, the partial curvature was still apparent, which necessitated placement of two tunica albuginea plication sutures along the ventral shaft. The penile curvature was corrected to 10 degrees dorsally at the end of the procedure. The remainder of his hospital course was unremarkable, and he was discharged home the same day.

His postoperative course was documented to be also uneventful, with minimal residual curvature noted during his two-month follow-up assessment. He denied any erectile dysfunction and was then able to obtain satisfactory erections without medications. He was sexually active with his partner and he denied pain or difficulty with intercourse.

Macroscopy pathology examination of the excised tissue had demonstrated multiple tan-white, elongated segments of glistening tissue with central areas of calcification that measured in aggregate 3.2 cm by 1.6 cm by 1.1 cm. The tissue was examined after decalcification. The hematoxylin and eosin histology sections revealed a centrally located bony tissue encompassed by penile fibrous tissue (see figure 2A). The bony tissue exhibited features of lamellar bone under polarized light (see figure 2B). No inflammation was found present within the lamellar bone and adjacent fibrous tissue. 

Figure 4. Radiograph of the penis showing ossification inside the septum and in both corpora cavernosa. A: Frontal view; B: Sagittal View. Reproduced from [24] under the Creative Commons Attribution License.

Figure 5. Photomicrograph of histological section from the lesion, showing metaplasia of bone tissue in the corpus spongiosum. Reproduced from [24] under the Creative Commons Attribution License.

Ustriyana et al. [28] stated the following: 

• Mineralized Francois de la Peyronie's plaque (MPP) impairs penile function. 
• The association, colocalization, and dynamic interplay between organic and inorganic constituents could provide insights into biomineralization of Peyronie's plaque. 

Ustriyana et al. [28] reported that human MPPs (n = 11) were surgically excised, and the organic and inorganic constituents were spatially mapped utilising multiple high-resolution imaging techniques. Multiscale image analyses resulted in spatial colocalization of elements within a highly porous material with heterogenous composition, lamellae, and osteocytic lacuna-like features with a morphological resemblance to bone. The lower (520 ± 179 mg/cc) and higher (1024 ± 155 mg/cc) mineral density regions were associated with higher (11%) and lower (7%) porosities in MPP. Energy dispersive X-ray and micro-X-ray fluorescent spectroscopic maps in the higher mineral density regions of MPP had revealed higher counts of calcium (Ca) and phosphorus (P), and a Ca/P ratio of 1.48 ± 0.06 similar to bone. More importantly, higher counts of zinc (Zn) were localized at the interface between softer (more organic to inorganic ratio) and harder (less organic to inorganic ratio) tissue regions of MPP and adjacent softer matrix, indicating the involvement of Zn-related proteins and/or pathways in the formation of MPP. In particular, dentin matrix protein-1 (DMP-1) was colocalized in a matrix rich in proteoglycans and collagen that contained osteocytic lacuna-like features. Ustriyana et al. [28] made the ensuing conclusion and statement of significance: 

• This combined materials science and biochemical with correlative micro-spectroscopic approach had provided insights into the plausible cellular and biochemical pathways that incite mineralization of an existing fibrous Peyronie's plaque.
• Aberrant human penile mineralization is known as mineralized Peyronie's plaque (MPP) and often emanates in a loss of form and function. 
• This study had focussed on investigating the spatial association of matrix proteins and elemental composition of MPP by colocalizing calcium, phosphorus, and trace metal zinc with dentin matrix protein 1 (DMP-1), acidic proteoglycans, and fibrillar collagen along with the cellular components using high resolution correlative micro-spectroscopy techniques. 
• Spatial maps provided insights into cellular and biochemical pathways which incite mineralization of fibrous Peyronie's plaque in humans. 

Hsu et al. [14] stated that in order to elucidate the anatomic distal ligament of the human glans penis and associated clinical implications, they compared the structures of the glans penis and corpora cavernosa in dogs, rats, and humans. From May 2001 to March 2003, gross dissection, microscopic examinations, and stains for elastic fibres and collagen subtypes were made in the penises of 11 adult human male cadavers, 7 dogs, and 5 rats. A distal ligament in the human glans penis replaced the os penis which is present in dogs or rats, also termed the baculum, but retained collagen types I and III as common structural and interlocking components, respectively. The intercavernosal septum was complete, and intracavernosal pillars (ICPs) were abundant in dogs, absent in rats, and moderately developed in humans. A tunica with numerous elastic fibres existed to fulfil the requirements of erectile function in humans but not in dogs or rats, since it was essential for establishing tissue strength to serve as a buttress. They would conclude as follows: 

• In dogs and rats, the strong os penis is designed for ready intromission and is associated with a pair of well-developed nonelastic corpora to serve as a buttress for the os penis. 
• These structures are necessary for the rigorous coitus observed in dogs. 
• The less compliant corpus cavernosum is suitable for the flipping action observed in a mating male rat. 
• These specific anatomical designs may provide explanations for the individual requirements for the specific physiologic functions that differ from species to species. 
• Even though there is no os in the human glans, a strong equivalent distal ligament is arranged centrally and acts as a supporting trunk for the glans penis. 
• Without this important structure, the glans could be too weak to bear the buckling pressure generated during coitus and too limber to serve as a patent passage for ejaculation, and it could be too difficult to transmit the intracavernosal pressure surge along the entire penis during ejaculation. 
• Given the common histological nature of the distal ligament, which is associated with the tunica albuginea and serves a similar function as the os penis observed in the dog and the rat, one may ask whether the healing process of a tunica may take as long as that required in a bony structure. 
• Further research is necessitated to answer this question.

Athanazio et al. [12] reported a 19-year-old patient, who had noticed a deep nodule within the dorsal side of his penis 2 years preceding his presentation. The nodule had been assessed clinically in other service. During this period, no skin lesions were noted. Over the preceding last months, the lesion had rapidly grown causing ulceration in his dorsal skin and invaded corpora cavernosa and corpus spongiosum (as evaluated by imaging studies). An incisional biopsy was undertaken showing a high-grade neoplasm with many non-neoplastic osteoclast-type multinucleated giant cells. An immunohistochemical panel study including SATB2 positivity in mononuclear cells had favoured sarcoma over sarcomatoid carcinoma. A partial penectomy without lymphadenectomy was undertaken (see figure 6) demonstrating a large tumour with pushing borders and 5-cm maximum diameter.

Figure 6: Gross appearance of penile osteosarcoma. Clinical appearance before surgery (A) and after resection and formalin fixation (B). Cut surface of the specimen. Fleshy tumour involving corpora cavernosa and corpus spongiosum. Upper left section shows uninvolved margin and bottom right shows the uninvolved distal glans (C). Reproduced from: [12] under the Creative Commons Attribution License.

The microscopy pathology examination findings of the penectomy specimen mirrored those of the incisional biopsy. The entire tumour was submitted for microscopic evaluation. The tumour had demonstrated highly pleomorphic sarcoma with epithelioid and fusiform cells intermixed with numerous non neoplastic osteoclast-type multinucleated giant cells (see figure 7). Necrosis was identified within < 10% of the whole tumour volume. There was brisk mitotic activity with 30 mitoses per 2 mm2. Angiolymphatic invasion was also identified. There was no clearcut foci of osteoid matrix; nevertheless, some foci of tumour cells demonstrated lace-like or trabecular deposition of matrix which was difficult to discern from collagenous stroma (see figure 8).

Figure 7: High-grade sarcoma with numerous non neoplastic osteoclast-type multinucleated giant cells (A: HE, 10x). It shows brisk mitotic activity (B: HE, 100x) and frequent atypical mitoses (C: HE, 400x). The whole tumour was submitted for histological analysis and few areas of equivocal osteoid matrix production were observed (C: 400x, HE stain). Atypical mononuclear cells show diffuse nuclear staining for SATB2 (E: 100x and F:400x) while only osteoclast-type multinucleated giant cells stained for marker of histiocytic differentiation, CD68 (G: 400x) Reproduced from [12] under the Creative Commons Attribution License

Figure 8: Equivocal areas of osteoid formation that may yield differential diagnosis with collagenous stroma (HE – A, 400x; B, 400x, C, 40x; D, 400x). Reproduced from [12] under the Creative Commons Attribution License

In both biopsy and penectomy specimen, atypical mononuclear cells were found to be diffusely positive for SATB2 (a marker of osteoblastic differentiation), CD99 and vimentin. These cells were negative for pan-keratin, GATA3, EMA, SOX10, S100 and ERG. Desmin was focally expressed. CD68 was expressed only in multinucleated giant (osteoclast-like) cells. The tumour cells had exhibited preserved INI1/SMARCB1 expression. See immunohistochemical photomicrographs in Figure 9.

Figure 9: Immunophenotype of a giant-cell rich penile osteosarcoma: no pan-keratin [removed]A, 40x), CD99 expression restricted to neoplastic cells (B, 40x), SATB2 expression in tumour cells (C, 40x; D, 400x), and CD68 positivity in giant osteoclast-type cells (E, 40x) Reproduced from [12] under the Creative Commons Attribution License

The radiology imaging studies had excluded any bone primary tumour. The patient had developed lung metastases after ten months of his follow up.

Athanazio et al. [12] made the ensuing educative discussions: 

• Special AT-rich sequence-binding protein 2 (SATB2) is a product of gene implicated in cleft palate defects (Berg & Schaeffer, 2017) [29]. 
• It is utilised in Diagnostic Pathology as a immunohistochemical marker that, among carcinomas, is sensitive and specific for colorectal and appendiceal primary sites. 
• It is also expressed in benign and malignant neoplasm with bone differentiation and, among neuroendocrine carcinoma, it is expressed in most Merkel cell carcinomas. 
• It is also usually expressed by epithelium of the lower gastrointestinal tract, brain, nongerminal centre lymphoid cells, ductal epithelium of the testis and epididymis.
• Among high-grade soft tissue sarcomas, SATB2 expression could be utilised as an indicative of extra-skeletal osteosarcomas with poor matrix production (Yamashita & Hameed, 2020) [30]   
• The recent new WHO Classification had stated that “SATB2 immunoreactivity could be useful for the detection of osteoblastic differentiation when immature osteoid is difficult to distinguish from collagenous stroma” (Yamashita & Hameed, 2020 [30].
• This tumour also exhibited focal areas of p63 expression. Staining was always weak. 
• Rather than evidence of squamous differentiation in this case, they had interpreted this feature as expected in giant cell tumours (both bone and soft tissue primaries) and osteoclast-rich osteosarcomas (Shooshtarizadeh et al., (2016) [31]; Jo & Fletcher, 2011) [32].
• Primary penile extra-skeletal osteosarcomas are exceedingly rare.
•  A recent report had also shown the feature of osteoclast-rich areas (Wu et al., 2012). [33] 
• The same is true for extra-skeletal osteosarcomas of other sites (Oh & Chang, (2017) [34].
• Penile primary extra-skeletal osteosarcoma is very rare and that would be the eighth described in English literature (Wu et al., 2012) [33]; (Bastian et al., 2003) [35]; (Fraser et al., 2000) [36]. 
• The first in which recently available SATB2 immunohistochemistry was helpful to identify osteoblastic differentiation. The 2-year evolution is a more protracted course than expected from osteosarcomas of the bone. Interestingly, other case of giant cell rich- extra-skeletal osteosarcoma of the penis was diagnosed as a small nodule (1.2 cm) with 1 year period of slow growth (Wu et al., 2012) [33].
• The main differential diagnosis in this case would be melanoma with osteosarcomatous differentiation and sarcomatoid carcinoma. 
• Melanoma was excluded by absent expression of S100 and SOX10. 
• Sarcomatoid carcinoma was considered in the differential diagnosis, but the patient had experienced a two-year growth of a deep palpable nodule with no relationship with penile skin or urethra. 
• The dorsal skin was ulcerated after rapid and recent growth. The urethra was uninvolved in the resection specimen, even though the erectile tissue of corpus spongiosum was infiltrated. The uninvolved urethra and lack of GATA3 expression argue against a sarcomatoid urothelial carcinoma. Pan-keratin was negative. P63 expression - as discussed above - cannot be used in the differential between squamous carcinoma and giant cell rich tumours of soft tissue. In addition, sarcomatoid squamous cell carcinoma is typically an HPV-independent neoplasm that are much more common in older patients. 
• Preserved INI1/SMARCB1 expression had argued against the diagnosis of epithelioid sarcoma.
• They had also considered the possibility of metastatic osteosarcoma. Radiology imaging of the skeleton, nevertheless, demonstrated no suspicious bone lesions.
• Soft tissue neoplasms of the penis are rare, and the incidence is difficult to estimate in view of the fact that these cases are mostly documented as case reports. 
• The most common benign soft tissue tumours of the penis are those with vascular differentiation including haemangioma (including epithelioid haemangioma), angiokeratomas an lymphangiomas. 
• The most common malignant sarcomas of the penis are leiomyosarcoma and vascular neoplasms (such as angiosarcoma, Kaposi sarcoma and epithelioid haemangioendothelioma) (Amin et al., 2014). [37] 
• Some recent examples of soft tissue malignancies reported as primary of the penis include Kaposi sarcoma in the set of HIV infection / transplant patients (Tammam et al., 2022) [38]; Anderson et al., (2021) [39], post-radiation sarcomas (Rodriguez-Perez et al., 2021) [40]; Hoyos et al., 2922) [41] and primitive neuroectodermal tumor (PNET)/Ewing’s sarcoma (Asari et al., 2021) [42]; (Krakorova et al., 2021) [43]; Estaphanous et al., (2022) [44]. 
• Differentiating true penile sarcomas from sarcomatoid carcinoma is crucial for prognosis and treatment, and this including even the proposed surgery since lymphadenectomy may considered for sarcomas but is obligatory for sarcomatoid carcinoma since 75–89%% of sarcomatoid squamous cell carcinomas of the penis show nodal metastasis at the time of diagnosis (Alvarado-Cabrero et al., 2022) [45].

Athanazio et al. [12] made the ensuing conclusions:

• In high-grade sarcomas, including in the penis, SATB2 staining might be useful to identify extra-skeletal osteosarcoma.

Wu et al. [33] stated the following: 

• Extra-skeletal osteosarcoma (EOS) is a malignant mesenchymal neoplasm which is located within soft tissues.
• It is a very rare disease, and accounts for only 4% of osteosarcoma and 1% of soft tissue sarcomas [46]. 
• Clinical diagnosis of EOS is difficult, X-ray, CT and magnetic resonance imaging (MRI) techniques might be helpful for the detection of the primary site, volume and relationship with the encompassing tissue of the tumour [47], and significant to the choice of operation. 
• Careful histopathology analysis is necessary to establish the final diagnosis.

Wu et al. [33] reported a 68-year-old man, who had manifested with a tender subcutaneous nodule of his penis. The nodule had localized pain and grown from about 0.3 cm × 0.3 cm × 0.3 cm to 1.2 cm × 0.8 cm × 0.5 cm in a year. Upon clinical examination, a 1.2 cm × 0.8 cm × 0.5 cm mass was palpated that measured 0.8 cm to the right to coronary sulcus. There was no red swelling of the skin and abnormal temperature. The edge of the mass was clear. The mobility of the mass was poor. The scrotum and testis of the patient were normal, and there was no touched intumescent lymph node in his inguinal region. The operation was undertaken in May, 2009. Wu et al. [33] stated that the patient received 1% Lidocaine injection at the root of his penis and the surgery was undertaken. The skin and subcutaneous tissue were dissected to segregate the mass. The tumour was noted to have slightly adhered to the encompassing tissue but did not invade to tunica albuginea. Finally, the mass was excised and a histological diagnosis was made. The patient was followed up for 10 months, and then lost to follow-up. Macroscopy examination of the specimen demonstrated that the neoplasm without envelope was greyish-white, greyish-pink and 1.5 cm×1 cm × 1 cm. The cut surface of the mass was greyish-white and rigid, and had sense of grit and no weaving shapes.

Microscopy examination of the specimen demonstrated that the cells within the tumour were widespread and irregular, mainly spindle and ovoid. The cytoplasm of the cells is basophilic. The nuclei were obviously atypical, mostly clostridial form and polygons. Massive bone matrix which coexisted with multinucleated giant cells could be found everywhere within the tumour. The tumour cells were noted to be in palisade arrangement and most commonly seen in and around the bone matrix. In some instances, 3.5 to dozen nuclei could be visualised in a single multinucleated giant cell.

Wu et al. [33] made the ensuing discussions:

• EOS is a malignant mesenchymal neoplasm which is located in soft tissues without direct attachment to skeletal system. 
• EOS was first reported by Wilson in 1941[48]. 
• It is extremely rare, and accounts for only 1% of soft tissue sarcomas. 
• Distinct to osteosarcoma usually afflicting young people, EOS mainly afflict people who are older than 50 years, and the mean age was 54.6 years and the ages of the patients had ranged between 16 years and 87 years) [49] [50]. 
• Trauma and radiotherapy are well- documented predisposing factors [51].
• Majority of people consider that multi-potential-mesenchymal cells develop to allotypic osteoblasts, that lead to the growth of EOS. 
• The precise origin was not clear. 
• EOS most commonly arises in the retroperitoneum and the muscles of thighs and limb girdles, rarely in lung, prostate gland, scalp, mammary gland, spermatic cord, pelvis and orbit. 
• EOS of the penis is very rare; only six other well-documented cases had been reported in the literature in English [52] [53] and none in Chinese. The main types are osteoblastoma, chondroblastoma and fibro- blastoma. 
• The tumour which is full of giant cells is extremely rare. There was no significant difference in clinical manifestation between EOS and other soft tissue sarcomas. 
• Localized swelling and pain are commonly encountered. 
• X-ray examination demonstrates scattered floccules or patchy high-density opacities in parenchyma, and the tumour has no connection with the adjacent bone tissue which is the characteristics of EOS. But the iconographic characteristic has no specificity. It is hard to be differentiated from with other malignant tumours, the final diagnosis must depend upon histopathologic examination.
• The volume of EOS has ranged from 2.5 to 20 cm3 and mostly lobulated, and 20% of the tumours were described as pseudo-encapsulated masses and with satellite nodules surrounded. The cut surface ranged from grey-white to tan-yellow to dark-red, depending upon the degree of mucification, haemorrhage, and necrosis. Some tumours demonstrated focal to cystic change. Except for the above-mentioned, there are some other subtypes such as: epithelioid osteosarcoma, clear-cell variant osteosarcoma, malignant fibrous histiocytoma and giant cells-rich osteosarcoma [54] [55] [56] [57]. They are all short of unique bio- characteristics, and have no significance to therapy and prognosis. The distribution mode, volume and number of nuclei of the giant cells they had reported were similar to those of giant cell tumours, and the number of osteoclast- like multinucleated giant cells increased obviously. But massive bone trabecula and allotypic tumour cells had more density and uniformity than the giant cells. According to the result of immunohistochemistry, they had concluded thar the tumour was the giant cell-rich type of EOS.
• Lee, et al. [46] introduced the diagnostic criteria of EOS as follows: (I) in soft tissue and not attached to bone or periosteum; (II) osteosarcoma with the same image; and (III) produce osteoid or cartilaginoid matrix. The case of giant cell-rich EOS should be distinguished from the following diseases in pathology: (I) Myositis ossificans: Patients usually have a history of trauma. Patients often have masses with the construction of active proliferation fibrous tissue, irregular osteoid tissue and mature trabecular bone. (II) Malignant mesenchymal tumours: In addition to components of osteosarcoma, it should also find other malignant mesenchymal elements, such as rhabdomyosarcoma, and liposarcoma. (III) Giant cell tumour: They both have affluent multinucleated giant cells, but giant cell tumour has no formation of tumorous bone trabeculae in spindle cells. (IV) Periosteal osteo- sarcoma: The mass is often located in the cortical bone surface, and closely integration and the formation of radial bone can be seen.
• EOS was reported to portend an exceptionally poor prognosis. 
• EOS is generally involved in invasion and metastasis. 
• The recurrence, transfer and 5-year survival rates were 45%, 65% and 25% to 37%, respectively. 
• In view of the fact that the exact preoperative clinical diagnosis is difficult, so patients with newly diagnosed EOS usually underwent local mass excision, and often died of metastasis of lung, liver, lymph nodes, bone or soft tissue in 2 to 3 years.

• Rare cases of ossification of penis tend to be reported sporadically and clinicians need to have a high index of suspicion for ossification within the penis in order to establish the diagnosis and to provide appropriate treatment for their patients. 

Conflict of Interest – None

Acknowledgements 

Acknowledgements to: 

• Canadian Urology Association Journal for granting permission for reproduction of figures and contents of their Journal article under the Creative Commons Attribution License. 
• Sao Paolo Medical Journal, for granting permission for reproduction of figures and contents of their Journal article under the Creative Commons Attribution License. 
• Surg Exp Pathology, Bio Med Central and Springer Nature for granting permission for reproduction of figures and contents of their Journal article under copy right: Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made.